Row Labels,in_text_citation,title,abstract,tabs
1,Kerr and Saryan 1986,Arsenic content of homeopathic medicines," In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations. Most sales personnel interviewed could not identify arsenic as being an ingredient in these preparations and were therefore incapable of warning the general public of possible dangers from ingestion. No such warnings appeared on the labels.","Arsenic content of homeopathic medicinesAbs: In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations. Most sales personnel interviewed could not identify arsenic as being an ingredient in these preparations and were therefore incapable of warning the general public of possible dangers from ingestion. No such warnings appeared on the labels."
2,Sorahan and Lancashire 1994,Lung cancer findings from the NIOSH study of United States cadmium recovery workers: A cautionary note," This brief article was designed to highlight two problems regarding the quality of job history data and estimates of cadmium (7440439) exposure used in previous studies on lung cancer mortality among workers from the Globe cadmium recovery factory. The first problem concerned inconsistencies in the definition of the NIOSH job history data. The second problem concerned the accuracy of the NIOSH job history data collected. Information from personnel and service records had been used to classify periods of employment into different cadmium exposure categories. Detailed information on job history was available from time sheets, but was not used in previous studies. Detailed job history data may be important in adjusting for any effect of arsenic (7440382) exposure. A comparison of time sheet job history data for April through August 1949 with general work categories for the same time period as found in the NIOSH database indicated that worker exposures had been misclassified. The current authors note that much more accurate job history data from time sheets is available which should be incorporated into future studies.","Lung cancer findings from the NIOSH study of United States cadmium recovery workers: A cautionary noteAbs: This brief article was designed to highlight two problems regarding the quality of job history data and estimates of cadmium (7440439) exposure used in previous studies on lung cancer mortality among workers from the Globe cadmium recovery factory. The first problem concerned inconsistencies in the definition of the NIOSH job history data. The second problem concerned the accuracy of the NIOSH job history data collected. Information from personnel and service records had been used to classify periods of employment into different cadmium exposure categories. Detailed information on job history was available from time sheets, but was not used in previous studies. Detailed job history data may be important in adjusting for any effect of arsenic (7440382) exposure. A comparison of time sheet job history data for April through August 1949 with general work categories for the same time period as found in the NIOSH database indicated that worker exposures had been misclassified. The current authors note that much more accurate job history data from time sheets is available which should be incorporated into future studies."
3,Lamm et al. 1992,Determinants of lung cancer risk among cadmium-exposed workers," Workers at a cadmium recovery plant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from 1943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substances other than cadmium. Feedstock ore concentrations were used as a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to 1940 was considerably higher than that of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Potential causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumulative cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight times more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium exposure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers.","Determinants of lung cancer risk among cadmium-exposed workersAbs: Workers at a cadmium recovery plant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from 1943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substances other than cadmium. Feedstock ore concentrations were used as a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to 1940 was considerably higher than that of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Potential causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumulative cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight times more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium exposure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers."
4,Zierler et al. 1988,Chemical quality of maternal drinking water and congenital heart disease," We undertook a case-control study to investigate the association between chemicals in maternal drinking water consumed during pregnancy and congenital heart disease in the offspring. Two hundred and seventy affected children and 665 healthy children were enrolled in the study. Information on contaminant levels in maternal drinking water was available from records of routine water analysis of samples taken from public taps in the communities where the mothers resided during pregnancy. Mothers provided information during a telephone interview on their health, pregnancy management, and demographic characteristics. Nine inorganic metals were analysed for detection of an association with congenital heart disease. The chemical exposures of particular interest were arsenic, lead, mercury and selenium. None of the chemicals was associated materially with an increase in the frequency of congenital heart disease overall. Arsenic exposure at any detectable level was associated with a threefold in-cre 3se in occurence of coarctation of the aorta (prevalence odds ratio = 3.4,95% confidence interval = 1.3-8.9). Detectable tracesof selenium in drinking water were associated with a lower frequency of any congenital heart disease than was observed among children exposed to drinking water not containing detectable levels of selenium (prevalence odds ratio = 0.62,95% confidence limits = 0.40-0.97). A dose-response effect was observed over four levels of selenium exposure. Non-differential errors in the measurement and classification of exposure to contaminants routinely monitored in drinking water could account for lack of positive findings. In addition, most of the contaminant levels were below the maximum levels set by the Environmental Protection Agency, so that lack of evidence of effect may have been due to the low exposure levels in this population.","Chemical quality of maternal drinking water and congenital heart diseaseAbs: We undertook a case-control study to investigate the association between chemicals in maternal drinking water consumed during pregnancy and congenital heart disease in the offspring. Two hundred and seventy affected children and 665 healthy children were enrolled in the study. Information on contaminant levels in maternal drinking water was available from records of routine water analysis of samples taken from public taps in the communities where the mothers resided during pregnancy. Mothers provided information during a telephone interview on their health, pregnancy management, and demographic characteristics. Nine inorganic metals were analysed for detection of an association with congenital heart disease. The chemical exposures of particular interest were arsenic, lead, mercury and selenium. None of the chemicals was associated materially with an increase in the frequency of congenital heart disease overall. Arsenic exposure at any detectable level was associated with a threefold in-cre 3se in occurence of coarctation of the aorta (prevalence odds ratio = 3.4,95% confidence interval = 1.3-8.9). Detectable tracesof selenium in drinking water were associated with a lower frequency of any congenital heart disease than was observed among children exposed to drinking water not containing detectable levels of selenium (prevalence odds ratio = 0.62,95% confidence limits = 0.40-0.97). A dose-response effect was observed over four levels of selenium exposure. Non-differential errors in the measurement and classification of exposure to contaminants routinely monitored in drinking water could account for lack of positive findings. In addition, most of the contaminant levels were below the maximum levels set by the Environmental Protection Agency, so that lack of evidence of effect may have been due to the low exposure levels in this population."
5,Seifert et al. 2000,The German Environmental Survey 1990/1992 (GerES II): A representative population study," The German Environmental Survey (GerES) is a large-scale population study which has repeatedly been carried out in Germany. GerES I was conducted in 1985 / 1986 followed by GerES ITs in 1990/1991 (West Germany) and GerES lib in 1991 / 1992 (East Germany). GerES Ill is currently run in both parts of Germany. The main goal of the surveys is to analyse and document the extent, distribution and determinants of the exposure to environmental pollutants of the German general population. Field work is conducted using a combination of several tools, including questionnaires, interviews, human biomonitoring, and indoor and outdoor environmental samplings. This paper describes the design of GerES II, and gives a general outline of the field work and the analytical procedures used. In GerES Il, about 4000 adults were representatively selected from the German population with regard to age, gender and community size. Approximately 700 children were also included. Arsenic, cadmium, copper, chromium, lead, and mercury were determined in blood, morning urine and/or scalp hair. In addition, samples were taken and analysed to characterise exposure in the domestic environment (indoor air, house dust, drinking water). The contribution to exposure of food was also studied. Exposure to volatile organic compounds (VOCs) was determined by personal sampling.","The German Environmental Survey 1990/1992 (GerES II): A representative population studyAbs: The German Environmental Survey (GerES) is a large-scale population study which has repeatedly been carried out in Germany. GerES I was conducted in 1985 / 1986 followed by GerES ITs in 1990/1991 (West Germany) and GerES lib in 1991 / 1992 (East Germany). GerES Ill is currently run in both parts of Germany. The main goal of the surveys is to analyse and document the extent, distribution and determinants of the exposure to environmental pollutants of the German general population. Field work is conducted using a combination of several tools, including questionnaires, interviews, human biomonitoring, and indoor and outdoor environmental samplings. This paper describes the design of GerES II, and gives a general outline of the field work and the analytical procedures used. In GerES Il, about 4000 adults were representatively selected from the German population with regard to age, gender and community size. Approximately 700 children were also included. Arsenic, cadmium, copper, chromium, lead, and mercury were determined in blood, morning urine and/or scalp hair. In addition, samples were taken and analysed to characterise exposure in the domestic environment (indoor air, house dust, drinking water). The contribution to exposure of food was also studied. Exposure to volatile organic compounds (VOCs) was determined by personal sampling."
6,Kleinfeld 1980,Arsine poisoning," A 31-year-old patient was admitted to the hospital because of dark red urine which on examination was found to be due to extracellular hemoglobin. The cause of the hemoglobinuria was exposure to arsine gas from a cylinder thought to be empty. The worker's exposure time was approximately one to two minutes. The degree of hemolytic anemia required only one unit of packed red cells. The patient was hydrated intravenously to avoid acute tubular necrosis. The arsenic content in the urine taken was 0.72 mg/L on the day of admission and dropped to 0.1 mg/L on the fourth day of hospitalization. The patient was discharged eight days after admission, when clinical and hematological status had improved sufficiently. Occupational history revealed that protective procedures employed in the handling of the cylinders containing the arsine gas were inadequate. It was found that the valve on one of the cylinders was half-opened and leaking and that the dust caps, which were attached to the outside of the valves of the cylinders, were present on some and not on others and, where present, had been hand-tightened and not wrench-tightened. Moreover, the cylinders although specified to be empty, were not, according to regulations requiring pressure to be less than 25 pounds gauge or 45 absolute.","Arsine poisoningAbs: A 31-year-old patient was admitted to the hospital because of dark red urine which on examination was found to be due to extracellular hemoglobin. The cause of the hemoglobinuria was exposure to arsine gas from a cylinder thought to be empty. The worker's exposure time was approximately one to two minutes. The degree of hemolytic anemia required only one unit of packed red cells. The patient was hydrated intravenously to avoid acute tubular necrosis. The arsenic content in the urine taken was 0.72 mg/L on the day of admission and dropped to 0.1 mg/L on the fourth day of hospitalization. The patient was discharged eight days after admission, when clinical and hematological status had improved sufficiently. Occupational history revealed that protective procedures employed in the handling of the cylinders containing the arsine gas were inadequate. It was found that the valve on one of the cylinders was half-opened and leaking and that the dust caps, which were attached to the outside of the valves of the cylinders, were present on some and not on others and, where present, had been hand-tightened and not wrench-tightened. Moreover, the cylinders although specified to be empty, were not, according to regulations requiring pressure to be less than 25 pounds gauge or 45 absolute."
7,Bencko & Symon 1977,Test of environmental exposure to arsenic and hearing changes in exposed children," Arsenic determination was carried out on hair, urine, and blood samples taken from groups of 10-year-old boys, each numbering 20 to 25 individuals, residing in a region polluted by arsenic. In all the examined materials considerably elevated concentrations of arsenic were found. The relation of the observed levels of arsenic to the distance of the place of residence up to a distance of more than 30 km from the source of the emissions was studied. On the basis of the results obtained, the most advantageous material for estimation of nonoccupational exposure to arsenic seems to be hair, in spite of some problems with the decontamination procedure involved. Considerable variability among individual arsenic values in the hair makes group examination a necessity. Hearing changes were analyzed in a group of 56 10-year old children residing near a power plant burning local coal of high arsenic content. The results of both audiometric and clinical examination were compared with those of control group numbering 51 children of the same age living outside the polluted area. The highly standardized audiometric and clinical examination were completed with a questionnaire analysis concerning the personal medical histories of the children. The obtained data were elaborated statistically by means of the chi(2)- test. In the case of air conduction, important hearing losses were found at frequencies of 125, 250 and 8000 Hz, especially at the lowest frequency range. Significant degrees of hearing loss were found in bone conduction as well as in the corresponding ranges of frequencies. The high statistical significance of the hearing impairments found points to very low probability of their being only an &quot;accidental&quot; finding. The possibility of toxic damage to the ear cannot yet be excluded.","Test of environmental exposure to arsenic and hearing changes in exposed childrenAbs: Arsenic determination was carried out on hair, urine, and blood samples taken from groups of 10-year-old boys, each numbering 20 to 25 individuals, residing in a region polluted by arsenic. In all the examined materials considerably elevated concentrations of arsenic were found. The relation of the observed levels of arsenic to the distance of the place of residence up to a distance of more than 30 km from the source of the emissions was studied. On the basis of the results obtained, the most advantageous material for estimation of nonoccupational exposure to arsenic seems to be hair, in spite of some problems with the decontamination procedure involved. Considerable variability among individual arsenic values in the hair makes group examination a necessity. Hearing changes were analyzed in a group of 56 10-year old children residing near a power plant burning local coal of high arsenic content. The results of both audiometric and clinical examination were compared with those of control group numbering 51 children of the same age living outside the polluted area. The highly standardized audiometric and clinical examination were completed with a questionnaire analysis concerning the personal medical histories of the children. The obtained data were elaborated statistically by means of the chi(2)- test. In the case of air conduction, important hearing losses were found at frequencies of 125, 250 and 8000 Hz, especially at the lowest frequency range. Significant degrees of hearing loss were found in bone conduction as well as in the corresponding ranges of frequencies. The high statistical significance of the hearing impairments found points to very low probability of their being only an &quot;accidental&quot; finding. The possibility of toxic damage to the ear cannot yet be excluded."
8,Brown and Chu 1983,A new method for the analysis of cohort studies: implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure," Implications of the multistage theory of carcinogenesis for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different patterns of excess risk related to duration of exposure, age at initial exposure, and follow-up time since exposure stopped, depending upon which stage of the carcinogenic process is affected by the carcinogen, i.e., action at an early stage or a late stage. New statistical methodologies are proposed to examine these patterns and are applied to the lung cancer mortality experience from a cohort study of smelter workers exposed to arsenic. Under this multistage hypothesis, the results indicate that arsenic exerts a definite late stage effect though an additional effect at the initial stage cannot be ruled out. The possibilities of biased conclusions resulting from incomplete exposure histories and lack of smoking information are also discussed as well as implications of these results to experimental animal studies.","A new method for the analysis of cohort studies: implications of the multistage theory of carcinogenesis applied to occupational arsenic exposureAbs: Implications of the multistage theory of carcinogenesis for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different patterns of excess risk related to duration of exposure, age at initial exposure, and follow-up time since exposure stopped, depending upon which stage of the carcinogenic process is affected by the carcinogen, i.e., action at an early stage or a late stage. New statistical methodologies are proposed to examine these patterns and are applied to the lung cancer mortality experience from a cohort study of smelter workers exposed to arsenic. Under this multistage hypothesis, the results indicate that arsenic exerts a definite late stage effect though an additional effect at the initial stage cannot be ruled out. The possibilities of biased conclusions resulting from incomplete exposure histories and lack of smoking information are also discussed as well as implications of these results to experimental animal studies."
9,Brown and Chu 1983,Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure," The multistage theory of carcinogenesis and its implications for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different relationships between excess carcinogenic risk and duration of exposure, age at initial exposure, and follow-up time since exposure stopped. These relationships are shown to depend on the stage of the carcinogenic process affected by the carcinogen, i.e., action at an early stage or a later stage. The patterns of excess lung cancer mortality were examined for a cohort of copper smelter workers exposed to atmospheric arsenic and other contaminants. Under this multistage hypothesis, the results indicate that arsenic appears to exert a definite effect on a late stage of the carcinogenic process, although an additional effect at the initial stage cannot be conclusively ruled out. Other factors, such as exposure to sulfur dioxide in the environment, calendar year at start of employment, and the potential bias resulting from incomplete exposure histories are also discussed as well as the implications of these results to experimental animal studies.","Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposureAbs: The multistage theory of carcinogenesis and its implications for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different relationships between excess carcinogenic risk and duration of exposure, age at initial exposure, and follow-up time since exposure stopped. These relationships are shown to depend on the stage of the carcinogenic process affected by the carcinogen, i.e., action at an early stage or a later stage. The patterns of excess lung cancer mortality were examined for a cohort of copper smelter workers exposed to atmospheric arsenic and other contaminants. Under this multistage hypothesis, the results indicate that arsenic appears to exert a definite effect on a late stage of the carcinogenic process, although an additional effect at the initial stage cannot be conclusively ruled out. Other factors, such as exposure to sulfur dioxide in the environment, calendar year at start of employment, and the potential bias resulting from incomplete exposure histories are also discussed as well as the implications of these results to experimental animal studies."
10,Buchet et al.  1980,Comparison of several methods for the determination of arsenic compounds in water and in urine: their application for the study of arsenic metabolism and for the monitoring of workers exposed to arsenic," Several methods for the determination of arsenic (7440382) and its chemical forms in urine were evaluated. Arsenic compounds tested were: diarsenic-trioxide (1327533) (As-(III)), diarsenic-pentoxide (1303282) (As-(V)), disodium-methyl-arsonate (144218) (MMA), cacodylic-acid (75605) (DMA), and arsanilic-acid (98500) (ARSAN). After various acid pretreatments, arsenic compounds were extracted in toluene and determined by electrothermal atomic absorption spectrometry (ET-AAS). As-(III) and A(V) were detected after acidification in the urine from industrial workers. Stability tests revealed that As-(III) was partly oxidized in urine. A dry ashing pretreatment technique using magnesium-oxide gave the most accurate determination of arsenic compounds in urine. Atomic absorption spectrometry (AG-AAS) was used for comparison to analyze total inorganic arsenic, MMA, and DMA. In urine samples of workers exposed to arsenic, good agreement was observed between total arsenic compounds determined by the ET-AAS and magnesium-oxide method and the AG-AAS method. When urine samples from people who consumed large amounts of fish were tested, arsenic compounds could not be detected by AG-AAS, but were detected by ET-AAS. The existence of a process of methylation of inorganic arsenic was confirmed. A biological halflife of 30 hours for arsenic and its metabolites was calculated. When arsenic originated from marine fauna, the halflife was reduced to 18 hours. The ET-AAS method gave an accurate measure of total arsenic compounds, but was not necessarily a measure of biologically active compounds. The authors conclude that AG-AAS was the most suitable method for the monitoring of arsenic exposure in workers, because it is not influenced by arsenic compounds formed from dietary habits, and can distinguish inorganic and dimethylated arsenic forms.","Comparison of several methods for the determination of arsenic compounds in water and in urine: their application for the study of arsenic metabolism and for the monitoring of workers exposed to arsenicAbs: Several methods for the determination of arsenic (7440382) and its chemical forms in urine were evaluated. Arsenic compounds tested were: diarsenic-trioxide (1327533) (As-(III)), diarsenic-pentoxide (1303282) (As-(V)), disodium-methyl-arsonate (144218) (MMA), cacodylic-acid (75605) (DMA), and arsanilic-acid (98500) (ARSAN). After various acid pretreatments, arsenic compounds were extracted in toluene and determined by electrothermal atomic absorption spectrometry (ET-AAS). As-(III) and A(V) were detected after acidification in the urine from industrial workers. Stability tests revealed that As-(III) was partly oxidized in urine. A dry ashing pretreatment technique using magnesium-oxide gave the most accurate determination of arsenic compounds in urine. Atomic absorption spectrometry (AG-AAS) was used for comparison to analyze total inorganic arsenic, MMA, and DMA. In urine samples of workers exposed to arsenic, good agreement was observed between total arsenic compounds determined by the ET-AAS and magnesium-oxide method and the AG-AAS method. When urine samples from people who consumed large amounts of fish were tested, arsenic compounds could not be detected by AG-AAS, but were detected by ET-AAS. The existence of a process of methylation of inorganic arsenic was confirmed. A biological halflife of 30 hours for arsenic and its metabolites was calculated. When arsenic originated from marine fauna, the halflife was reduced to 18 hours. The ET-AAS method gave an accurate measure of total arsenic compounds, but was not necessarily a measure of biologically active compounds. The authors conclude that AG-AAS was the most suitable method for the monitoring of arsenic exposure in workers, because it is not influenced by arsenic compounds formed from dietary habits, and can distinguish inorganic and dimethylated arsenic forms."
11,Valentine et al. 1979,"Arsenic levels in human blood, urine, and hair in response to exposure via drinking water"," Five communities with water supplies having arsenic concentrations of 6, 51, 98, 123, and 393 ?g/liter were selected for study. Samples of blood, hair, urine, and tap water were obtained from participants in each community and analyzed for arsenic content. Results showed an increase in arsenic concentration for urine and hair samples as the water arsenic concentrations increased. Arsenic levels in blood did not show this trend until chronic toxicity was expected. We conclude that arsenic levels in water at concentrations of 100 ?g/liter or less seem not to produce an undue body burden.","Arsenic levels in human blood, urine, and hair in response to exposure via drinking waterAbs: Five communities with water supplies having arsenic concentrations of 6, 51, 98, 123, and 393 ?g/liter were selected for study. Samples of blood, hair, urine, and tap water were obtained from participants in each community and analyzed for arsenic content. Results showed an increase in arsenic concentration for urine and hair samples as the water arsenic concentrations increased. Arsenic levels in blood did not show this trend until chronic toxicity was expected. We conclude that arsenic levels in water at concentrations of 100 ?g/liter or less seem not to produce an undue body burden."
12,Cuzick et al. 1982,Medicinal arsenic and internal malignancies," A mortality analysis has been carried out on a cohort of patients given Fowler's solution (potassium arsenite) for periods ranging from 2 weeks to 12 years between 1945 and 1969. An excess of fatal and non-fatal skin cancer was apparent, but there was no overall excess mortality from cancer. Further analyses by site of cancer, dose level, and time from first exposure are also presented. A subset of patients were examined in 1969-70 for the presence of arsenical keratoses, hyperpigmentation and skin cancer. About half the patients had one or more of these signs. Although the cancer mortality of this entire subgroup was similar to the expected value, all the cancer deaths occurred in patients with prior signs of arsenicism. These data suggest that while any excess of internal malignancy due to the use of Fowler's solution is small or non-existent, there may be a susceptible subgroup which can be identified from dermatological manifestations.","Medicinal arsenic and internal malignanciesAbs: A mortality analysis has been carried out on a cohort of patients given Fowler's solution (potassium arsenite) for periods ranging from 2 weeks to 12 years between 1945 and 1969. An excess of fatal and non-fatal skin cancer was apparent, but there was no overall excess mortality from cancer. Further analyses by site of cancer, dose level, and time from first exposure are also presented. A subset of patients were examined in 1969-70 for the presence of arsenical keratoses, hyperpigmentation and skin cancer. About half the patients had one or more of these signs. Although the cancer mortality of this entire subgroup was similar to the expected value, all the cancer deaths occurred in patients with prior signs of arsenicism. These data suggest that while any excess of internal malignancy due to the use of Fowler's solution is small or non-existent, there may be a susceptible subgroup which can be identified from dermatological manifestations."
13,Done and Peart 1971,Acute toxicities of arsenical herbicides, ,Acute toxicities of arsenical herbicidesAbs: 
14,Enterline & Marsh 1982,Cancer among workers exposed to arsenic and other substances in a copper smelter," A study of the mortality experience of 2802 men who worked one year or more during the period 1940-4964 at a copper smelter in Tacoma, Washington, where arsenic exposure occurred showed a twofold excess in respiratory cancer deaths. Using a time-weighted measure of exposure, a life table method for accumulating dose, and a 10-year lag period, the excess ranged from 1.5 in the lowest exposure category to 2.5 in the highest exposure category. Neither duration of exposure nor time since first exposure contributed strongly to the respiratory cancer excess. The twofold excess in respiratory cancer deaths held for workers with relatively short exposures (less than 10 years) and with a relatively short latency period (less than 20 years) as well as for those with longer exposure and latent periods. This appeared to be because the respiratory cancer excess tended to disappear with time for workers who terminated employment alive, and because workers in high-exposure jobs tended to terminate more quickly than workers in low-exposure jobs. A somewhat unorthodox analytic method showed a weak relationship between the respiratory cancer excess and exposure duration when exposure intensity was held constant. Here, arsenic exposure intensity made an independent contribution to the respiratory cancer excess.","Cancer among workers exposed to arsenic and other substances in a copper smelterAbs: A study of the mortality experience of 2802 men who worked one year or more during the period 1940-4964 at a copper smelter in Tacoma, Washington, where arsenic exposure occurred showed a twofold excess in respiratory cancer deaths. Using a time-weighted measure of exposure, a life table method for accumulating dose, and a 10-year lag period, the excess ranged from 1.5 in the lowest exposure category to 2.5 in the highest exposure category. Neither duration of exposure nor time since first exposure contributed strongly to the respiratory cancer excess. The twofold excess in respiratory cancer deaths held for workers with relatively short exposures (less than 10 years) and with a relatively short latency period (less than 20 years) as well as for those with longer exposure and latent periods. This appeared to be because the respiratory cancer excess tended to disappear with time for workers who terminated employment alive, and because workers in high-exposure jobs tended to terminate more quickly than workers in low-exposure jobs. A somewhat unorthodox analytic method showed a weak relationship between the respiratory cancer excess and exposure duration when exposure intensity was held constant. Here, arsenic exposure intensity made an independent contribution to the respiratory cancer excess."
15,Falk et al. 1981,Arsenic-related hepatic angiosarcoma," Data from several small autopsy series in German vintners in the 1940s and 1950s and a number of case reports have previously suggested that arsenic is a cause of hepatic angiosarcoma (HAS). In a nationwide review of deaths from HAS in the United States, we identified seven cases with a history of prolonged use of Fowler's solution (inorganic potassium arsenite), which provide further support for the association of arsenic exposure and HAS. An epidemiologic study of a cohort of individuals treated long-term with Fowler's solution might confirm this association.","Arsenic-related hepatic angiosarcomaAbs: Data from several small autopsy series in German vintners in the 1940s and 1950s and a number of case reports have previously suggested that arsenic is a cause of hepatic angiosarcoma (HAS). In a nationwide review of deaths from HAS in the United States, we identified seven cases with a history of prolonged use of Fowler's solution (inorganic potassium arsenite), which provide further support for the association of arsenic exposure and HAS. An epidemiologic study of a cohort of individuals treated long-term with Fowler's solution might confirm this association."
16,Feussner et al.  1979,Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis," A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.","Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysisAbs: A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements."
17,Freeman and Couch 1978,Prolonged encephalopathy with arsenic poisoning, A case of prolonged reversible encephalopathy in a woman with arsenic poisoning is described. Previous descriptions of extended encephalopathy due to arsenic are rare.,Prolonged encephalopathy with arsenic poisoningAbs: A case of prolonged reversible encephalopathy in a woman with arsenic poisoning is described. Previous descriptions of extended encephalopathy due to arsenic are rare.
18,Garb and Hine 1977,Arsenical neuropathy: residual effects following acute industrial exposure," A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed.","Arsenical neuropathy: residual effects following acute industrial exposureAbs: A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed."
19,Gerhardt et al. 1978,Chronic renal insufficiency from cortical necrosis induced by arsenic poisoning," A 39-year-old man had anuria and azotemia and was found to be suffering from acute arsenic poisoning. After two peritoneal dialyses, partial renal function returned, and the patient has survived for five years without dialysis. Renal cortical necrosis was demonstrated by renal biopsy and renal calcification. We suggest that arsenic be added to the list of substances capable of causing renal cortical necrosis and recommend consideration of this complication in cases of arsenical poisoning.","Chronic renal insufficiency from cortical necrosis induced by arsenic poisoningAbs: A 39-year-old man had anuria and azotemia and was found to be suffering from acute arsenic poisoning. After two peritoneal dialyses, partial renal function returned, and the patient has survived for five years without dialysis. Renal cortical necrosis was demonstrated by renal biopsy and renal calcification. We suggest that arsenic be added to the list of substances capable of causing renal cortical necrosis and recommend consideration of this complication in cases of arsenical poisoning."
20,Gilbert et al. 1990,Effects of pentachlorophenol and other chemical preservatives on the health of wood-treating workers in Hawaii," The morbidity and mortality of workers occupationally exposed to wood treating chemicals used in Hawaii for the years 1960 to 1981 were evaluated. The specific chemical exposures investigated were CCA (chromated copper-arsenate), TBTO (tributyl tin oxide) and PCP (pentachlorophenol). Results of detailed medical histories, laboratory and physiological tests, and physical examinations of 88 wood treaters were compared with those of 58 matched controls. The occupationally exposed cases had a significantly higher mean level of urinary PCP as compared to the controls (mean of 174 ppb vs. 35 ppb, micrograms/kg). There were no significant differences between the groups for the other urinary pesticide residues. The medical histories and physical examinations revealed no significant variations between the wood treaters and the comparison group. Review of all organ systems and laboratory data showed no clinically significant differences between exposed and nonexposed cohorts, although elevated hepatic enzymes in both groups merit further study. The results indicated no adverse health effects or increased incidence of mortality resulting from exposure to wood preservative chemicals in wood treaters who had worked in the industry for 0.33 to 26.3 years with a median of 6.5 years. Only 6 deaths were reported, 5 of cardiovascular disease, one of cause undetermined and none of cancer. Total number of deaths were less than the 8 anticipated for this age group.","Effects of pentachlorophenol and other chemical preservatives on the health of wood-treating workers in HawaiiAbs: The morbidity and mortality of workers occupationally exposed to wood treating chemicals used in Hawaii for the years 1960 to 1981 were evaluated. The specific chemical exposures investigated were CCA (chromated copper-arsenate), TBTO (tributyl tin oxide) and PCP (pentachlorophenol). Results of detailed medical histories, laboratory and physiological tests, and physical examinations of 88 wood treaters were compared with those of 58 matched controls. The occupationally exposed cases had a significantly higher mean level of urinary PCP as compared to the controls (mean of 174 ppb vs. 35 ppb, micrograms/kg). There were no significant differences between the groups for the other urinary pesticide residues. The medical histories and physical examinations revealed no significant variations between the wood treaters and the comparison group. Review of all organ systems and laboratory data showed no clinically significant differences between exposed and nonexposed cohorts, although elevated hepatic enzymes in both groups merit further study. The results indicated no adverse health effects or increased incidence of mortality resulting from exposure to wood preservative chemicals in wood treaters who had worked in the industry for 0.33 to 26.3 years with a median of 6.5 years. Only 6 deaths were reported, 5 of cardiovascular disease, one of cause undetermined and none of cancer. Total number of deaths were less than the 8 anticipated for this age group."
21,Harrington et al. 1978,"A survey of a population exposed to high concentrations of arsenic in well water in Fairbanks, Alaska"," Following the discovery of high concentrations of arsenic (up to 10,000 µg/liter) In the well water of a residential area near Fairbanks, Alaska, an epidemiologic study was undertaken in September, 1976, to assess exposure, absorption, and clinical sequelae of chronic arsenic ingestion. Two hundred eleven (91%) of 232 area residents completed questionnaires relating to water consumption history and to the signs and symptoms of arsenicalism. Physical examinations were conducted, and complete blood counts performed. Urine, hair, nail, and well water samples were analyzed for arsenic content. Urine arsenic levels above 2 µg/100 ml were found in 130/198 (66%) of the study population. Hair arsenic levels above 1 µg/g occurred in 74/181 (41%), and nail arsenic levels above 4 µg/g In 49/132 (37%). In well-water drinkers, a close correlation was found between well water arsenic levels and levels of arsenic In urine (r = 0.58, p < 10–8). Mean urine arsenic levels (17.83 µg/100 ml) In persons who drank well water containing 100µg arsenic/liter were significantly greater than levels in bottled-water drinkers or In well-water drinkers exposed to <100µg arsenic/liter (mean 4.09 µg/100 ml; p < 10–10). Hair arsenic levels also correlated positively with well water arsenic levels (r = 0.43; p < 10–6), but may have reflected external contamination of hair during washing. Nail arsenic levels correlated poorly with well water arsenic exposure. Despite the chronic Increased exposure of the study population to arsenic, no clinical or hematologic abnormalities were found. Although the study did not consider long-term carcinogenic effects, based on the water level of arsenic (100 µg/liter) above which urine arsenic In drinkers Increases, the EPA standard (50 µg/liter) seems reasonable and conservative.","A survey of a population exposed to high concentrations of arsenic in well water in Fairbanks, AlaskaAbs: Following the discovery of high concentrations of arsenic (up to 10,000 µg/liter) In the well water of a residential area near Fairbanks, Alaska, an epidemiologic study was undertaken in September, 1976, to assess exposure, absorption, and clinical sequelae of chronic arsenic ingestion. Two hundred eleven (91%) of 232 area residents completed questionnaires relating to water consumption history and to the signs and symptoms of arsenicalism. Physical examinations were conducted, and complete blood counts performed. Urine, hair, nail, and well water samples were analyzed for arsenic content. Urine arsenic levels above 2 µg/100 ml were found in 130/198 (66%) of the study population. Hair arsenic levels above 1 µg/g occurred in 74/181 (41%), and nail arsenic levels above 4 µg/g In 49/132 (37%). In well-water drinkers, a close correlation was found between well water arsenic levels and levels of arsenic In urine (r = 0.58, p < 10–8). Mean urine arsenic levels (17.83 µg/100 ml) In persons who drank well water containing 100µg arsenic/liter were significantly greater than levels in bottled-water drinkers or In well-water drinkers exposed to <100µg arsenic/liter (mean 4.09 µg/100 ml; p < 10–10). Hair arsenic levels also correlated positively with well water arsenic levels (r = 0.43; p < 10–6), but may have reflected external contamination of hair during washing. Nail arsenic levels correlated poorly with well water arsenic exposure. Despite the chronic Increased exposure of the study population to arsenic, no clinical or hematologic abnormalities were found. Although the study did not consider long-term carcinogenic effects, based on the water level of arsenic (100 µg/liter) above which urine arsenic In drinkers Increases, the EPA standard (50 µg/liter) seems reasonable and conservative."
22,Harrisson et al. 1958,Acute oral toxicity and chemical and physical properties of arsenic trioxides, ,Acute oral toxicity and chemical and physical properties of arsenic trioxidesAbs: 
23,Heydorn 1970,Environmental variation of arsenic levels in human blood determined by neutron activation analysis," Arsenic levels in blood plasma and red cells from patients with Blackfoot disease, a peripheral arteriosclerosis endemic to a small area in Taiwan, were studied in relation to healthy individuals from the same and other parts of Taiwan and compared with arsenic levels in a control group from Denmark. Arsenic was determined by neutron activation analysis with radiochemical separation and re-irradiation yield determination. The precision and accuracy of the results have been carefully evaluated in order to permit quantitative tests for the significance of the observed differences. The results from Taiwan followed a logarithmic normal distribution, and no difference was found between Blackfoot patients and their healthy family members. However, their overall arsenic levels were higher than the Taiwan average, presumably because of arsenic in their drinking water. Much lower levels were found in Denmark, which geochemically belongs to a soil zone with less arsenic than Taiwan.","Environmental variation of arsenic levels in human blood determined by neutron activation analysisAbs: Arsenic levels in blood plasma and red cells from patients with Blackfoot disease, a peripheral arteriosclerosis endemic to a small area in Taiwan, were studied in relation to healthy individuals from the same and other parts of Taiwan and compared with arsenic levels in a control group from Denmark. Arsenic was determined by neutron activation analysis with radiochemical separation and re-irradiation yield determination. The precision and accuracy of the results have been carefully evaluated in order to permit quantitative tests for the significance of the observed differences. The results from Taiwan followed a logarithmic normal distribution, and no difference was found between Blackfoot patients and their healthy family members. However, their overall arsenic levels were higher than the Taiwan average, presumably because of arsenic in their drinking water. Much lower levels were found in Denmark, which geochemically belongs to a soil zone with less arsenic than Taiwan."
24,Welch et al. 1982,"Arsenic exposure, smoking, and respiratory cancer in copper smelter workers"," A report by Lee and Fraumeni in 1969 linked exposure to arsenic and other contaminants to a threefold excess of respiratory cancer among 8,047 employees at the Anaconda copper smelter. We established vital status through December 1977 for a sample of 1,800 men from the original cohort. Average arsenic concentrations were estimated for each smelter department based on industrial hygiene measurements made from 1943 to 1965. Departments with similar concentrations were combined into four categories of exposure: 1) low (less than 100 micrograms/m3), 2) medium (100-499 micrograms/m3), 3) high (500-4,999 micrograms/m3) and 4) very high (greater than or equal to 5,000 micrograms/m3). Three indices of individual arsenic exposure were developed: time-weighted average, 30-day ceiling, and cumulative. Exposures to sulfur dioxide and asbestos were also examined. Smoking habits were obtained by questionnaire. Mortality was compared to that of men in the State of Montana using the modified lifetable method. A clear dose-response relationship between arsenic exposure and respiratory cancer was demonstrated. Men in the highest exposure category had a sevenfold excess. Those in the low and medium categories had a risk close to that expected. Ceiling arsenic exposure appeared to be more important than did time-weighted average exposure. Sulfur dioxide and asbestos did not appear to be important in the excess of respiratory cancer, although sulfur dioxide and arsenic exposures could not be separated completely. Smoking did not appear to be as important as arsenic exposure. Our findings suggest that had men worked only in departments with low or medium arsenic exposures (i.e., less than 500 micrograms/m3) there would have been little excess respiratory cancer. Since the estimates of arsenic exposure were based on department averages rather than on concentrations for individual jobs, these results must be interpreted with caution.","Arsenic exposure, smoking, and respiratory cancer in copper smelter workersAbs: A report by Lee and Fraumeni in 1969 linked exposure to arsenic and other contaminants to a threefold excess of respiratory cancer among 8,047 employees at the Anaconda copper smelter. We established vital status through December 1977 for a sample of 1,800 men from the original cohort. Average arsenic concentrations were estimated for each smelter department based on industrial hygiene measurements made from 1943 to 1965. Departments with similar concentrations were combined into four categories of exposure: 1) low (less than 100 micrograms/m3), 2) medium (100-499 micrograms/m3), 3) high (500-4,999 micrograms/m3) and 4) very high (greater than or equal to 5,000 micrograms/m3). Three indices of individual arsenic exposure were developed: time-weighted average, 30-day ceiling, and cumulative. Exposures to sulfur dioxide and asbestos were also examined. Smoking habits were obtained by questionnaire. Mortality was compared to that of men in the State of Montana using the modified lifetable method. A clear dose-response relationship between arsenic exposure and respiratory cancer was demonstrated. Men in the highest exposure category had a sevenfold excess. Those in the low and medium categories had a risk close to that expected. Ceiling arsenic exposure appeared to be more important than did time-weighted average exposure. Sulfur dioxide and asbestos did not appear to be important in the excess of respiratory cancer, although sulfur dioxide and arsenic exposures could not be separated completely. Smoking did not appear to be as important as arsenic exposure. Our findings suggest that had men worked only in departments with low or medium arsenic exposures (i.e., less than 500 micrograms/m3) there would have been little excess respiratory cancer. Since the estimates of arsenic exposure were based on department averages rather than on concentrations for individual jobs, these results must be interpreted with caution."
25,Holmqvist 1951,Occupational arsenical dermatitis: a study among employees at a copper ore smelting work including investigations of skin reactions to contact with arsenic compounds,"<div><font face=""Times New Roman"" size=3 color=black>BIOSIS COPYRIGHT: BIOL ABS. Objectives The purpose of this study was to search for evidence of an association between occupational arsenic exposure and diabetes mellitus, as implied by the relation of this disease to arsenic in drinking water in a recent study from Taiwan. Methods A case-referent analysis on death records of 5498 individuals in the art glass producing part of southeastern Sweden was performed. Out of all the enrolled subjects, 888 were glass workers. According to occupational title, glassblowers, foundry workers, and unspecified workers were regarded as potentially exposed to arsenic. Persons with a diagnosis of diabetes mellitus either as an underlying or contributing cause of death were considered cases. Referents were decedents without any indication of cancer, cardiovascular disease, or diabetes. Results A slightly elevated risk (Mantel-Haenszel odds ratio (MH-OR) 1.2, 95% confidence interval 95% CI) 0.82-1.8) was found for diabetes mellitus among the glassworks employees, esp </font></div>","Occupational arsenical dermatitis: a study among employees at a copper ore smelting work including investigations of skin reactions to contact with arsenic compoundsAbs:<div><font face=""Times New Roman"" size=3 color=black>BIOSIS COPYRIGHT: BIOL ABS. Objectives The purpose of this study was to search for evidence of an association between occupational arsenic exposure and diabetes mellitus, as implied by the relation of this disease to arsenic in drinking water in a recent study from Taiwan. Methods A case-referent analysis on death records of 5498 individuals in the art glass producing part of southeastern Sweden was performed. Out of all the enrolled subjects, 888 were glass workers. According to occupational title, glassblowers, foundry workers, and unspecified workers were regarded as potentially exposed to arsenic. Persons with a diagnosis of diabetes mellitus either as an underlying or contributing cause of death were considered cases. Referents were decedents without any indication of cancer, cardiovascular disease, or diabetes. Results A slightly elevated risk (Mantel-Haenszel odds ratio (MH-OR) 1.2, 95% confidence interval 95% CI) 0.82-1.8) was found for diabetes mellitus among the glassworks employees, esp </font></div>"
26,Jelinek and Corneliussen 1977,Levels of arsenic in the United States food supply," At the present time, the Food and Drug Administration (FDA) accords the highest priority to mercury, lead, cadmium, arsenic, selenium, and zinc in its program on toxic elements in foods. The only regulatory levels for arsenic in foods in the U. S. are the tolerances which have been established for its residues in specified foods, resulting from the application of arsenical pesticides on food and feed crops and from animal feed additives. FDA has monitored for arsenic in its Total Diet Survey since the inception of this program. The data from this program indicate that the average daily intake for arsenic (as As(2)O(3)) has decreased from about 130 mug/day in 1968 to about 20 mug/day in 1974. Most of the arsenic is found in the meat-fish-poultry food class of the total diet. In individual foods, the highest levels were found in fish, with a mean level of about 1.5 ppm (as As(2)O(3)) in the edible portion of finfish. Much lower levels were found in all the other food types analyzed; of these, the highest levels found were a mean level of 0.08 ppm in chicken and 0.16 ppm in rice. FDA toxicologists do not believe that the average daily intake of arsenic, or its levels in the different food commodities, pose a hazard to the consumer.","Levels of arsenic in the United States food supplyAbs: At the present time, the Food and Drug Administration (FDA) accords the highest priority to mercury, lead, cadmium, arsenic, selenium, and zinc in its program on toxic elements in foods. The only regulatory levels for arsenic in foods in the U. S. are the tolerances which have been established for its residues in specified foods, resulting from the application of arsenical pesticides on food and feed crops and from animal feed additives. FDA has monitored for arsenic in its Total Diet Survey since the inception of this program. The data from this program indicate that the average daily intake for arsenic (as As(2)O(3)) has decreased from about 130 mug/day in 1968 to about 20 mug/day in 1974. Most of the arsenic is found in the meat-fish-poultry food class of the total diet. In individual foods, the highest levels were found in fish, with a mean level of about 1.5 ppm (as As(2)O(3)) in the edible portion of finfish. Much lower levels were found in all the other food types analyzed; of these, the highest levels found were a mean level of 0.08 ppm in chicken and 0.16 ppm in rice. FDA toxicologists do not believe that the average daily intake of arsenic, or its levels in the different food commodities, pose a hazard to the consumer."
27,Kelynack et al. 1900,Arsenical poisoning from beer-drinking," Report is presented of several cases of peripheral neuritis in heavy beer drinkers from several English districts. The condition was believed at first to be due to alcohol consumption but later determined to be arsenical (7440382) poisoning due to the use of sulfuric-acid (7664939) in the manufacture of brewing sugars. Data are given for the effects of the arsenical poisoning on the skin, and on the nervous, respiratory, circulatory, digestive and urinary systems, and for recommended medical treatment.","Arsenical poisoning from beer-drinkingAbs: Report is presented of several cases of peripheral neuritis in heavy beer drinkers from several English districts. The condition was believed at first to be due to alcohol consumption but later determined to be arsenical (7440382) poisoning due to the use of sulfuric-acid (7664939) in the manufacture of brewing sugars. Data are given for the effects of the arsenical poisoning on the skin, and on the nervous, respiratory, circulatory, digestive and urinary systems, and for recommended medical treatment."
28,Larsen et al. 1979,"Topographical distribution of arsenic, manganese, and selenium in the normal human brain"," The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brain from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron activation analysis with radiochemical separation. Distinct patterns of distribution were shown for each of the 3 elements. Variations between individuals were found for some but not all brain areas, resulting in coefficients of variation between individuals of about 30% for arsenic, 10% for manganese and 20% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue.","Topographical distribution of arsenic, manganese, and selenium in the normal human brainAbs: The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brain from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron activation analysis with radiochemical separation. Distinct patterns of distribution were shown for each of the 3 elements. Variations between individuals were found for some but not all brain areas, resulting in coefficients of variation between individuals of about 30% for arsenic, 10% for manganese and 20% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue."
29,Lee and Fraumeni 1969,Arsenic and respiratory cancer in man: an occupational study,0,Arsenic and respiratory cancer in man: an occupational studyAbs:0
30,Lubin et al. 1981,Respiratory cancer among copper smelter workers: recent mortality statistics," A survey of mortality among copper smelter workers in the western United States revealed that a respiratory cancer excess previously observed during the period 1938 through 1963 continued from 1964 through 1977. When analyzed in relation to smelter employment prior to 1964, the recent increase in respiratory cancer was linked to work in plant areas where airborne arsenic concentrations were elevated and to a cumulative arsenic exposure index, although some excess risk was also associated with long-term employment in jobs with limited exposures to arsenic. The arsenic-related excess remained after adjustment for work in areas of the plant with elevated concentrations of sulphur dioxide, which was not found to have an independent influence upon cancer risk. Increased rates for nonmalignant respiratory disease were also observed, but were not significantly associated with arsenic exposure.","Respiratory cancer among copper smelter workers: recent mortality statisticsAbs: A survey of mortality among copper smelter workers in the western United States revealed that a respiratory cancer excess previously observed during the period 1938 through 1963 continued from 1964 through 1977. When analyzed in relation to smelter employment prior to 1964, the recent increase in respiratory cancer was linked to work in plant areas where airborne arsenic concentrations were elevated and to a cumulative arsenic exposure index, although some excess risk was also associated with long-term employment in jobs with limited exposures to arsenic. The arsenic-related excess remained after adjustment for work in areas of the plant with elevated concentrations of sulphur dioxide, which was not found to have an independent influence upon cancer risk. Increased rates for nonmalignant respiratory disease were also observed, but were not significantly associated with arsenic exposure."
31,Milham 1977,Studies of morbidity near a copper smelter," Children living near a copper smelter in Tacoma, Washington, have been shown to have increased levels of urinary and hair arsenic. Studies of hearing, blood status and school attendance in exposed and nonexposed children failed to detect any differences in these parameters.","Studies of morbidity near a copper smelterAbs: Children living near a copper smelter in Tacoma, Washington, have been shown to have increased levels of urinary and hair arsenic. Studies of hearing, blood status and school attendance in exposed and nonexposed children failed to detect any differences in these parameters."
32,Milham and Strong 1974,Human arsenic exposure in relation to a copper smelter,"HEEP COPYRIGHT: BIOL ABS. Children living near a copper smelter in Tacoma, Washington, USA, had increased levels of As in hair and urine. The urinary As level decreased with distance of residence from the smelter stack. House vacuum-cleaner dust showed a similar distance relationship. Urine As levels in children varied synchronously over a 5-wk period, indicating that inhalation was the most likely exposure route. In children urinary As level showed an inverse relationship to age, with younger children showing consistently higher urine As levels. A death-record analysis indicated an increased respiratory cancer incidence in men working at this smelter. Since published urinary As levels for men working at this smelter were similar to those seen in people residing near the smelter, the community surrounding the smelter might be exposed to an increased respiratory cancer risk. Accordingly, action was taken to reduce As emissions from the smelter.","Human arsenic exposure in relation to a copper smelterAbs:HEEP COPYRIGHT: BIOL ABS. Children living near a copper smelter in Tacoma, Washington, USA, had increased levels of As in hair and urine. The urinary As level decreased with distance of residence from the smelter stack. House vacuum-cleaner dust showed a similar distance relationship. Urine As levels in children varied synchronously over a 5-wk period, indicating that inhalation was the most likely exposure route. In children urinary As level showed an inverse relationship to age, with younger children showing consistently higher urine As levels. A death-record analysis indicated an increased respiratory cancer incidence in men working at this smelter. Since published urinary As levels for men working at this smelter were similar to those seen in people residing near the smelter, the community surrounding the smelter might be exposed to an increased respiratory cancer risk. Accordingly, action was taken to reduce As emissions from the smelter."
33,Morris et al. 1974,Arsenic and noncirrhotic portal hypertension,0,Arsenic and noncirrhotic portal hypertensionAbs:0
34,Morton et al. 1976,"Skin cancer and water arsenic in Lane County, Oregon"," It was expected that the incidence of skin cancer would be related to the known high arsenic levels in water supplies of Lane County, Oregon. Incidence rates were based on all histopathologically confirmed cases among Lane County residents diagnosed during 1958-1971 and were compared to mean water arsenic levels measured during 1968-1974. Basal cell carcinoma had a mean annual incidence rate of 88 per 100,000, a 5:4::M:F sex ratio, and an increasing risk for both sexes in urban areas. Squamous cell carcinoma incidence was 50 per 100,000 and showed 2:1:M:F sex ratio but no urban predilection. Neither type of skin cancer was directly related to the arsenic levels as expected, although sporadic individuals with sufficient exposure could manifest the relationship. Fewer than expected drinking water sources were found to contain high arsenic content, so that the Lane County data do not necessarily contradict previous reports of positive correlation. The basal cell carcinoma pattern suggested that this disease might be potentiated by urban air pollutants.","Skin cancer and water arsenic in Lane County, OregonAbs: It was expected that the incidence of skin cancer would be related to the known high arsenic levels in water supplies of Lane County, Oregon. Incidence rates were based on all histopathologically confirmed cases among Lane County residents diagnosed during 1958-1971 and were compared to mean water arsenic levels measured during 1968-1974. Basal cell carcinoma had a mean annual incidence rate of 88 per 100,000, a 5:4::M:F sex ratio, and an increasing risk for both sexes in urban areas. Squamous cell carcinoma incidence was 50 per 100,000 and showed 2:1:M:F sex ratio but no urban predilection. Neither type of skin cancer was directly related to the arsenic levels as expected, although sporadic individuals with sufficient exposure could manifest the relationship. Fewer than expected drinking water sources were found to contain high arsenic content, so that the Lane County data do not necessarily contradict previous reports of positive correlation. The basal cell carcinoma pattern suggested that this disease might be potentiated by urban air pollutants."
35,Nordenson et al. 1981,Chromosome aberrations in cultured human lymphocytes exposed to trivalent and pentavalent arsenic," Cultured human lymphocytes were exposed to trivalent (NaASO2) and pentavalent (Na2HAsO4) arsenic in concentrations comparable to the arsenic levels found in the urine of copper smelter workers. Significantly increased frequencies of chromosome aberrations (gaps, chromatid breaks, chromatid exchanges and chromosome breaks) were found after exposure to trivalent but not pentavalent arsenic. This effect was not found when nonstimulated (GO) lymphocytes were exposed to trivalent arsenic and then cultured. The rate of sister chromatid exchanges was also found to be increased after exposure to trivalent arsenic. Thus results suggest that trivalent arsenic is more genotoxic than pentavalent arsenic and that arsenic exerts its effect mainly during cell division.","Chromosome aberrations in cultured human lymphocytes exposed to trivalent and pentavalent arsenicAbs: Cultured human lymphocytes were exposed to trivalent (NaASO2) and pentavalent (Na2HAsO4) arsenic in concentrations comparable to the arsenic levels found in the urine of copper smelter workers. Significantly increased frequencies of chromosome aberrations (gaps, chromatid breaks, chromatid exchanges and chromosome breaks) were found after exposure to trivalent but not pentavalent arsenic. This effect was not found when nonstimulated (GO) lymphocytes were exposed to trivalent arsenic and then cultured. The rate of sister chromatid exchanges was also found to be increased after exposure to trivalent arsenic. Thus results suggest that trivalent arsenic is more genotoxic than pentavalent arsenic and that arsenic exerts its effect mainly during cell division."
36,Pershagen et al. 1977,Mortality in a region surrounding an arsenic emitting plant," The purpose of the investigation is to study whether an increased mortality from certain causes exists in an area around the Rönnskärsverken smelter works in northern Sweden. Founded in 1928, this metallurgical plant processing mainly nonferrous metals has since its initial operations been using ore with a high arsenic content. This has resulted in environmental pollution to air and water of arsenic, as well as other metals and sulfur dioxide. The causes of death for the population of two parishes in the vicinity of the plant were listed from the National Sedish Register on Death Causes. A reference area in the same part of Sweden with similar degree of urbanization, occupational profile, and age distribution was chosen. The causes of death for the two populations were followed during a period of 14 yr. A significantly higher mortality rate for lung cancer was noted in men in the exposed area. However, this increase was no longer significant when the occupationally exposed at Rönnskärsverken were excluded. The latter showed a highly significant excess mortality due to primary respiratory cancer.A continuation of this investigation in the form of a cohort study of both the mortality and cancer incidence is currently under way.","Mortality in a region surrounding an arsenic emitting plantAbs: The purpose of the investigation is to study whether an increased mortality from certain causes exists in an area around the Rönnskärsverken smelter works in northern Sweden. Founded in 1928, this metallurgical plant processing mainly nonferrous metals has since its initial operations been using ore with a high arsenic content. This has resulted in environmental pollution to air and water of arsenic, as well as other metals and sulfur dioxide. The causes of death for the population of two parishes in the vicinity of the plant were listed from the National Sedish Register on Death Causes. A reference area in the same part of Sweden with similar degree of urbanization, occupational profile, and age distribution was chosen. The causes of death for the two populations were followed during a period of 14 yr. A significantly higher mortality rate for lung cancer was noted in men in the exposed area. However, this increase was no longer significant when the occupationally exposed at Rönnskärsverken were excluded. The latter showed a highly significant excess mortality due to primary respiratory cancer.A continuation of this investigation in the form of a cohort study of both the mortality and cancer incidence is currently under way."
37,Pinto et al. 1977,Mortality experience in relation to a measured arsenic trioxide exposure," This report examines the mortality experience of 527 men who retired from a copper smelter where they were exposed to airborne arsenic trioxide. Urinary arsenic values of all plant employees were determined in 1973, and the relative arsenic exposure in the various departments of the plant were determined. The relationship of airborne arsenic concentrations to urinary arsenic values was studied in a separate experiment, and the feasibility of using urinary arsenic values as a measure of arsenic exposure was established. The mortality experience of the cohort under study showed them to have a mortality 12.2% higher than was found for males of the same area at the same ages and in the same time period. The excess mortality was due chiefly to respiratory cancer. When the deaths were classified by total lifetime arsenic exposure, the respiratory cancer mortality was linearly related to the amount of exposure. The 1973 figures for arsenic exposure underestimated the exposure of the cohort group by a factor of possibly 10. Evidence was obtained which suggests that after removal from arsenic exposure, the risk of lung cancer declines. Certain of the data which are presented suggests there may be a threshold value for airborne arsenic trioxide exposure below which no adverse effects may be expected.","Mortality experience in relation to a measured arsenic trioxide exposureAbs: This report examines the mortality experience of 527 men who retired from a copper smelter where they were exposed to airborne arsenic trioxide. Urinary arsenic values of all plant employees were determined in 1973, and the relative arsenic exposure in the various departments of the plant were determined. The relationship of airborne arsenic concentrations to urinary arsenic values was studied in a separate experiment, and the feasibility of using urinary arsenic values as a measure of arsenic exposure was established. The mortality experience of the cohort under study showed them to have a mortality 12.2% higher than was found for males of the same area at the same ages and in the same time period. The excess mortality was due chiefly to respiratory cancer. When the deaths were classified by total lifetime arsenic exposure, the respiratory cancer mortality was linearly related to the amount of exposure. The 1973 figures for arsenic exposure underestimated the exposure of the cohort group by a factor of possibly 10. Evidence was obtained which suggests that after removal from arsenic exposure, the risk of lung cancer declines. Certain of the data which are presented suggests there may be a threshold value for airborne arsenic trioxide exposure below which no adverse effects may be expected."
38,Pinto et al. 1978,Mortality experience of arsenic-exposed workers," The mortality experience of all pensioners from a copper smelter who were aged 65 or over between 1949 and 1973 has been studied. An index of arsenic exposure was developed for all operations in the plant for 1973. This was applied to all individuals studied so that a comparative measure could be made of each individual's working-life exposure to arsenic. The overall mortality of this cohort was 12.2% higher than for males living in the same area, of the same ages, and in the same time periods. The excess mortality was due chiefly to respiratory cancer where mortality was three times the expected. Because other contaminants were present in the atmosphere, it is not certain that arsenic was entirely responsible for the respiratory cancer observed, yet a close association with arsenic seems highly likely.","Mortality experience of arsenic-exposed workersAbs: The mortality experience of all pensioners from a copper smelter who were aged 65 or over between 1949 and 1973 has been studied. An index of arsenic exposure was developed for all operations in the plant for 1973. This was applied to all individuals studied so that a comparative measure could be made of each individual's working-life exposure to arsenic. The overall mortality of this cohort was 12.2% higher than for males living in the same area, of the same ages, and in the same time periods. The excess mortality was due chiefly to respiratory cancer where mortality was three times the expected. Because other contaminants were present in the atmosphere, it is not certain that arsenic was entirely responsible for the respiratory cancer observed, yet a close association with arsenic seems highly likely."
39,Poma et al. 1981,Cytogenetic analysis of bone marrow cells and spermatogonia of male mice after in vivo treatment with arsenic," HEEP COPYRIGHT: BIOL ABS. Male Swiss Albino mice were injected i.p. with an As2O3 solution (0, 4, 8 and 12 mg As/kg) and sacrificed 12, 24, 36 and 48 h after injection. Neither chromatid nor chromosome aberrations were observed in bone marrow cells and spermatogonia.","Cytogenetic analysis of bone marrow cells and spermatogonia of male mice after in vivo treatment with arsenicAbs: HEEP COPYRIGHT: BIOL ABS. Male Swiss Albino mice were injected i.p. with an As2O3 solution (0, 4, 8 and 12 mg As/kg) and sacrificed 12, 24, 36 and 48 h after injection. Neither chromatid nor chromosome aberrations were observed in bone marrow cells and spermatogonia."
40,Reymann et al. 1978,Relationship between arsenic intake and internal malignant neoplasms," An attempt has been made to assess the carcinogenic effect of arsenic intake by analyzing a group of patients who were treated with arsenic for various skin diseases in the 1930s. When compared with the expected incidence of malignant internal neoplasms, based on figures obtained from the Danish Cancer Registry, a significant increase in the incidence of internal malignant neoplasms was observed in females with multiple basal cell carcinomas. A group comprising 53 patients with arsenic keratoses presented a considerable increase in the incidence of internal malignant neoplasms. However, these patients were so specifically selected that no regular statistical analysis can be made of this group. It may be said that arsenic has a carcinogenic effect even in the relatively small doses applied in dermatological therapy.","Relationship between arsenic intake and internal malignant neoplasmsAbs: An attempt has been made to assess the carcinogenic effect of arsenic intake by analyzing a group of patients who were treated with arsenic for various skin diseases in the 1930s. When compared with the expected incidence of malignant internal neoplasms, based on figures obtained from the Danish Cancer Registry, a significant increase in the incidence of internal malignant neoplasms was observed in females with multiple basal cell carcinomas. A group comprising 53 patients with arsenic keratoses presented a considerable increase in the incidence of internal malignant neoplasms. However, these patients were so specifically selected that no regular statistical analysis can be made of this group. It may be said that arsenic has a carcinogenic effect even in the relatively small doses applied in dermatological therapy."
41,Roat et al. 1982,Hepatic angiosarcoma associated with short-term arsenic ingestion," In a 45 year old man, hepatic angiosarcoma developed 33 years after medicinal arsenic ingestion of only six months' duration. In addition, the patient had a history of basal cell carcinomas without having had excessive sunlight exposure. Factor VIII staining of the tumor supports an endothelial cell origin of the tumor. The development of skin cancers and hepatic angiosarcoma in this patient suggests that there may be no safe threshold of arsenic exposure. A careful history concerning even short-term arsenic exposure in all patients with hepatic angiosarcoma may uncover more examples of this association.","Hepatic angiosarcoma associated with short-term arsenic ingestionAbs: In a 45 year old man, hepatic angiosarcoma developed 33 years after medicinal arsenic ingestion of only six months' duration. In addition, the patient had a history of basal cell carcinomas without having had excessive sunlight exposure. Factor VIII staining of the tumor supports an endothelial cell origin of the tumor. The development of skin cancers and hepatic angiosarcoma in this patient suggests that there may be no safe threshold of arsenic exposure. A careful history concerning even short-term arsenic exposure in all patients with hepatic angiosarcoma may uncover more examples of this association."
42,Rossner et al. 1977,Effect of the combined action of selenium and arsenic on suspension culture of mice fibroblasts," The protective influence of arsenic against the toxic action of selenium has been tested on suspension cultures of mice fibroblasts LA 115. The growth of the cells was observed after the isolated and combined action of sodium arsenite NaAsO2 and sodium selenite Na2SeO3. The concentration range of both substances in cultivation medium MEm (USOL) was 10(-5) -10(-11)M. The growth of treated cultures was analyzed daily during 5 days of exposure. From the results obtained, growth curves of the cell cultures were constructed and analyzed. The results of every determination were evaluated in relation to the corresponding control culture. The results obtained demonstrate that decreasing concentrations of arsenic enhanced its protective effect in the range of the concentrations used. In contrast, a low protective effect of selenium against arsenic was noted in the concentrations employed. The cell cultures have proved to be very suitable for toxicological studies of the combined effects of different substances.","Effect of the combined action of selenium and arsenic on suspension culture of mice fibroblastsAbs: The protective influence of arsenic against the toxic action of selenium has been tested on suspension cultures of mice fibroblasts LA 115. The growth of the cells was observed after the isolated and combined action of sodium arsenite NaAsO2 and sodium selenite Na2SeO3. The concentration range of both substances in cultivation medium MEm (USOL) was 10(-5) -10(-11)M. The growth of treated cultures was analyzed daily during 5 days of exposure. From the results obtained, growth curves of the cell cultures were constructed and analyzed. The results of every determination were evaluated in relation to the corresponding control culture. The results obtained demonstrate that decreasing concentrations of arsenic enhanced its protective effect in the range of the concentrations used. In contrast, a low protective effect of selenium against arsenic was noted in the concentrations employed. The cell cultures have proved to be very suitable for toxicological studies of the combined effects of different substances."
43,Selby et al. 1977,Epidemiology and toxicology of arsenic poisoning in domestic animals," Arsenic poisoning is one of the more important causes of heavy metal poisoning in domestic animals. Two species--dogs and cattle--are intoxicated more frequently than other animals; yet sporadic instances of poisoning have been observed in cats, horses, and pigs. Cases observed by veterinary clinicians are either peracute, acute, or chronic intoxications. Frequently the initial and only indication that a severe problem exists with peracute poisoning in a cattle herd is dead animals. Chronic intoxications are also observed in cattle. Acute intoxication is the most common form of arsenic poisoning observed and documented in the dog. Also intoxicated dogs were younger, i.e., 2-6 months of age. Arsenic is a severe alimentary tract irritant in domestic animals, and treatment in most instances consists mainly of symptomatic and supportive treatment. The source of intoxication, when it can be determined, is usually dips, sprays, powders, or vegetation contaminated by pesticides containing arsenic.","Epidemiology and toxicology of arsenic poisoning in domestic animalsAbs: Arsenic poisoning is one of the more important causes of heavy metal poisoning in domestic animals. Two species--dogs and cattle--are intoxicated more frequently than other animals; yet sporadic instances of poisoning have been observed in cats, horses, and pigs. Cases observed by veterinary clinicians are either peracute, acute, or chronic intoxications. Frequently the initial and only indication that a severe problem exists with peracute poisoning in a cattle herd is dead animals. Chronic intoxications are also observed in cattle. Acute intoxication is the most common form of arsenic poisoning observed and documented in the dog. Also intoxicated dogs were younger, i.e., 2-6 months of age. Arsenic is a severe alimentary tract irritant in domestic animals, and treatment in most instances consists mainly of symptomatic and supportive treatment. The source of intoxication, when it can be determined, is usually dips, sprays, powders, or vegetation contaminated by pesticides containing arsenic."
44,Smith et al. 1976,The chemistry of sulfur and arsenic in airborne copper smelter particulates, HEEP COPYRIGHT: BIOL ABS. UTAH USA,The chemistry of sulfur and arsenic in airborne copper smelter particulatesAbs: HEEP COPYRIGHT: BIOL ABS. UTAH USA
45,Sommers & Mcmanus 1953,Multiple arsenical cancers of skin and internal organs," Twenty seven persons are reported who are exposed to iatrogenic or occupational arsenic (7440382) and developed typical arsenical keratoses, skin cancers that were frequently multiple, and sometimes internal cancers ascribed to arsenic etiology. The skin was the most common cancer site, but urogenital, oral, esophageal, and metaplastic squamous respiratory epithelium also occasionally produced carcinomas. A few internal cancers were found in endocrine stimulated organs. An unusual variety of skin carcinomas was observed at sites of arsenic localization such as the epidermis, sweat, or sebaceous glands. Also observed were epidermal atrophy, hyperplasia, precancerous changes, Bowen's disease, and invasive cancers.","Multiple arsenical cancers of skin and internal organsAbs: Twenty seven persons are reported who are exposed to iatrogenic or occupational arsenic (7440382) and developed typical arsenical keratoses, skin cancers that were frequently multiple, and sometimes internal cancers ascribed to arsenic etiology. The skin was the most common cancer site, but urogenital, oral, esophageal, and metaplastic squamous respiratory epithelium also occasionally produced carcinomas. A few internal cancers were found in endocrine stimulated organs. An unusual variety of skin carcinomas was observed at sites of arsenic localization such as the epidermis, sweat, or sebaceous glands. Also observed were epidermal atrophy, hyperplasia, precancerous changes, Bowen's disease, and invasive cancers."
46,Tokudome and Kuratsune 1976,A cohort study on mortality from cancer and other causes among workers at a metal refinery," A non-concurrent prospective study was made on deaths from cancer and other causes occurring among 2,675 male workers at a metal refinery from 1949 to 1971. The expected number of deaths computed by applying age- and cause-specific death rates of Japanese males to these workers was compared with the observed number of deaths. Among 839 copper smelters, significantly increased mortalities were noted for lung cancer (SMR = 1,189) and colon cancer, but nor for cancer of the stomach, liver (primary) and biliary passages, pancreas and skin or for leukemia, tuberculosis, cerebrovascular diseases, heart diseases and liver cirrhosis. A dose-response relationship was demonstrated between the mortality from lung cancer and the degree of exposure. A very high excess mortality from lung cancer (SMR = 2,500) was seen among copper smelters who were considered to have been most heavily exposed to arsenic or workers who had engaged in sintering and blast furnace operations for 15 years of more before 1949. The latent period of lung cancer was 37.6 years on average, and not related to level of exposure. Twenty-six of 29 deaths from lung cancer among copper smelters occurred after they had left the refinery. Other production workers and clerical workers showed no significant excess mortality from any kind of cancer.","A cohort study on mortality from cancer and other causes among workers at a metal refineryAbs: A non-concurrent prospective study was made on deaths from cancer and other causes occurring among 2,675 male workers at a metal refinery from 1949 to 1971. The expected number of deaths computed by applying age- and cause-specific death rates of Japanese males to these workers was compared with the observed number of deaths. Among 839 copper smelters, significantly increased mortalities were noted for lung cancer (SMR = 1,189) and colon cancer, but nor for cancer of the stomach, liver (primary) and biliary passages, pancreas and skin or for leukemia, tuberculosis, cerebrovascular diseases, heart diseases and liver cirrhosis. A dose-response relationship was demonstrated between the mortality from lung cancer and the degree of exposure. A very high excess mortality from lung cancer (SMR = 2,500) was seen among copper smelters who were considered to have been most heavily exposed to arsenic or workers who had engaged in sintering and blast furnace operations for 15 years of more before 1949. The latent period of lung cancer was 37.6 years on average, and not related to level of exposure. Twenty-six of 29 deaths from lung cancer among copper smelters occurred after they had left the refinery. Other production workers and clerical workers showed no significant excess mortality from any kind of cancer."
47,Westhoff et al. 1975,Arsenic intoxication as a cause of megaloblastic anemia," We have described a case of chronic arsenic intoxication associated with pancytopenia and megaloblastic erythropoiesis. The patient had the typical laboratory manifestations of effective erythorpoiesis due to a megaloblastic process, including macroovalocytes, mild pancytopenia, low reticulocyte index, increased marrow cellularity with erythroid hyperplasia, and morphologic evidence of megaloblastic maturation in the marrow. The patient's serum folate and vitamin B12 were normal, and the anemia regressed without therapy. Our case suggests that the combination of megaloblastosis with normoblastic or megaloblastic karyorrhexis,should raise the suspicion of arsenic intoxication in the mind of the observer. In addition, arsenic should be added to the list of agents causing a reversible megaloblastic anemia.","Arsenic intoxication as a cause of megaloblastic anemiaAbs: We have described a case of chronic arsenic intoxication associated with pancytopenia and megaloblastic erythropoiesis. The patient had the typical laboratory manifestations of effective erythorpoiesis due to a megaloblastic process, including macroovalocytes, mild pancytopenia, low reticulocyte index, increased marrow cellularity with erythroid hyperplasia, and morphologic evidence of megaloblastic maturation in the marrow. The patient's serum folate and vitamin B12 were normal, and the anemia regressed without therapy. Our case suggests that the combination of megaloblastosis with normoblastic or megaloblastic karyorrhexis,should raise the suspicion of arsenic intoxication in the mind of the observer. In addition, arsenic should be added to the list of agents causing a reversible megaloblastic anemia."
48,Chhuttani et al. 1967,Arsenical neuropathy,0,Arsenical neuropathyAbs:0
49,Ch'i and Blackwell 1968,"A controlled retrospective study of Blackfoot disease, an endemic peripheral gangrene disease in Taiwan",NULL,"A controlled retrospective study of Blackfoot disease, an endemic peripheral gangrene disease in TaiwanAbs:NULL"
50,Beckett et al. 1986,Acute encephalopathy due to occupational exposure to arsenic," Case study of a chemical engineer who developed severe psychiatric symptoms after prolonged exposure to arsenic in an antimony smelter. Though urinary and hair arsenic content were higher than normal for exposed workers, the major reason for suspecting acute arsenic intoxication was the presence of psychiatric symptoms: hallucinations, disorientation, delirium and memory loss. Because the patient had a history of psychiatric illness 28 years previously, it is suggested that he had an abnormal susceptibility to the central nervous effects of arsenic.","Acute encephalopathy due to occupational exposure to arsenicAbs: Case study of a chemical engineer who developed severe psychiatric symptoms after prolonged exposure to arsenic in an antimony smelter. Though urinary and hair arsenic content were higher than normal for exposed workers, the major reason for suspecting acute arsenic intoxication was the presence of psychiatric symptoms: hallucinations, disorientation, delirium and memory loss. Because the patient had a history of psychiatric illness 28 years previously, it is suggested that he had an abnormal susceptibility to the central nervous effects of arsenic."
51,Bencko 1977,"Carcinogenic, teratogenic, and mutagenic effects of arsenic"," This review outlines briefly the history and present status of the problem of carcinogenic, teratogenic and mutagenic effects of arsenic. Discrepancies between clinical observations and positive results of epidemiological studies and the experimental induction of cancer by arsenic are discussed. The present knowledge of the mechanism of teratogenic and mutagenic effects of arsenic is analyzed. The growing importance of arsenic as an environmental pollutant is demonstrated. Continuation of throughly organized epidemiological studies in regions with excessive arsenic exposure of the population and standardization of an epidemiological approach to this problem on an international basis are recommended. New approaches in experimental studies of the carcinogenicity of arsenic in combination with other known or suspected carcinogens are recommended as well.","Carcinogenic, teratogenic, and mutagenic effects of arsenicAbs: This review outlines briefly the history and present status of the problem of carcinogenic, teratogenic and mutagenic effects of arsenic. Discrepancies between clinical observations and positive results of epidemiological studies and the experimental induction of cancer by arsenic are discussed. The present knowledge of the mechanism of teratogenic and mutagenic effects of arsenic is analyzed. The growing importance of arsenic as an environmental pollutant is demonstrated. Continuation of throughly organized epidemiological studies in regions with excessive arsenic exposure of the population and standardization of an epidemiological approach to this problem on an international basis are recommended. New approaches in experimental studies of the carcinogenicity of arsenic in combination with other known or suspected carcinogens are recommended as well."
52,Carpenter 1987,Developmental analysis of cephalic axial dysraphic disorders in arsenic-treated hamster embryos," Parenteral injection of pregnant golden hamsters with inorganic arsenic salts early in gestation results, by term, in markedly elevated embryonic-fetal mortality (approximately equal to 50%) and, in surviving fetuses, a high (approximately equal to 90%) incidence of cephalic axial dysraphic disorders (&quot;neural tube defects&quot;), particularly exencephaly/anencephaly and encephaloceles. The present investigation traces the day by day development of these embryopathic effects of arsenic in the hamster with an emphasis on the pathogenesis of cephalic axial dysraphic disorders. Pregnant golden hamsters were given an intraperitoneal injection of sodium arsenate (20 mg/kg) on the 8th day (08.00) of their 16 day gestation period. Matched control dams were injected with an equivalent volume of distilled water by the same route and at the same stage of gestation. Experimental and control dams were sacrificed beginning 24 h after treatment and at regular daily intervals thereafter until term. Embryos and fetuses delivered from sacrificed dams were examined for abnormalities both grossly and histologically. In embryos delivered earliest after treatment (24-48 h) the principal deleterious effect of arsenic observed was retarded growth (elevation, approximation, and fusion) of the cephalic neural folds. This growth retardation ranged in severity among embryos. In the most severely afflicted there was a site wherein the opposing cephalic neural folds had completely failed to appose and fuse (&quot;closure&quot;). This failure of closure of all four tissue components of the neural folds (surface ectoderm, paraxial mesoderm, neural crest cells, neuroectoderm) resulted in a persistent dorsal opening in the head, i.e., cranioschisis aperta. The extent and appearance of this opening varied from a small, ovoid aperture in the dorsal midbrain (mesencephalic) region of the head to a widely open cleft involving the fore and hindbrain regions as well as the midbrain region. In less severely afflicted early embryos, the cephalic neural folds had elevated and met in the dorsal midline but had only incompletely fused, i.e., cranioschisis occulta. Microscopic study of these latter embryos revealed that in the affected region(s), complete closure of the surface ectoderm component of the neural folds had taken place, but only partial closure of the mesoderm, neural crest and neuroectoderm components. The different types of cephalic axial dysraphic disorders presenting in arsenic-treated fetuses delivered at later gestational stages (predominantly exencephaly and encephaloceles) could all be traced back and related to one or the other of these early forms of disturbed neurulation.","Developmental analysis of cephalic axial dysraphic disorders in arsenic-treated hamster embryosAbs: Parenteral injection of pregnant golden hamsters with inorganic arsenic salts early in gestation results, by term, in markedly elevated embryonic-fetal mortality (approximately equal to 50%) and, in surviving fetuses, a high (approximately equal to 90%) incidence of cephalic axial dysraphic disorders (&quot;neural tube defects&quot;), particularly exencephaly/anencephaly and encephaloceles. The present investigation traces the day by day development of these embryopathic effects of arsenic in the hamster with an emphasis on the pathogenesis of cephalic axial dysraphic disorders. Pregnant golden hamsters were given an intraperitoneal injection of sodium arsenate (20 mg/kg) on the 8th day (08.00) of their 16 day gestation period. Matched control dams were injected with an equivalent volume of distilled water by the same route and at the same stage of gestation. Experimental and control dams were sacrificed beginning 24 h after treatment and at regular daily intervals thereafter until term. Embryos and fetuses delivered from sacrificed dams were examined for abnormalities both grossly and histologically. In embryos delivered earliest after treatment (24-48 h) the principal deleterious effect of arsenic observed was retarded growth (elevation, approximation, and fusion) of the cephalic neural folds. This growth retardation ranged in severity among embryos. In the most severely afflicted there was a site wherein the opposing cephalic neural folds had completely failed to appose and fuse (&quot;closure&quot;). This failure of closure of all four tissue components of the neural folds (surface ectoderm, paraxial mesoderm, neural crest cells, neuroectoderm) resulted in a persistent dorsal opening in the head, i.e., cranioschisis aperta. The extent and appearance of this opening varied from a small, ovoid aperture in the dorsal midbrain (mesencephalic) region of the head to a widely open cleft involving the fore and hindbrain regions as well as the midbrain region. In less severely afflicted early embryos, the cephalic neural folds had elevated and met in the dorsal midline but had only incompletely fused, i.e., cranioschisis occulta. Microscopic study of these latter embryos revealed that in the affected region(s), complete closure of the surface ectoderm component of the neural folds had taken place, but only partial closure of the mesoderm, neural crest and neuroectoderm components. The different types of cephalic axial dysraphic disorders presenting in arsenic-treated fetuses delivered at later gestational stages (predominantly exencephaly and encephaloceles) could all be traced back and related to one or the other of these early forms of disturbed neurulation."
53,Chen et al. 1992,"Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water"," In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.","Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking waterAbs: In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation."
54,Farmer and Johnson 1990,Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic," An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases.","Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenicAbs: An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases."
55,Feinglass 1973,Arsenic intoxication from well water in the United States," Perhaps no substance has had historical notoriety equal to that of arsenic. Nevertheless, its use in medicinal compounds has been widespread since antiquity, and occupational exposure has been common, particularly in the first half of this century. Its greatest use has been in the production of pesticides and herbicides, and a substantial number of accidental deaths have occurred from ingestion of these substances. Despite its ubiquity in the environment, arsenic intoxication in the United States secondary to a contaminated water supply is rare. In the 11 cases reported below, acute and subacute arsenic intoxication was related to ingestion of well water.","Arsenic intoxication from well water in the United StatesAbs: Perhaps no substance has had historical notoriety equal to that of arsenic. Nevertheless, its use in medicinal compounds has been widespread since antiquity, and occupational exposure has been common, particularly in the first half of this century. Its greatest use has been in the production of pesticides and herbicides, and a substantial number of accidental deaths have occurred from ingestion of these substances. Despite its ubiquity in the environment, arsenic intoxication in the United States secondary to a contaminated water supply is rare. In the 11 cases reported below, acute and subacute arsenic intoxication was related to ingestion of well water."
56,Fernandez-Sola et al. 1991,Acute arsenical myopathy: morphological description," We describe the histological findings of the muscle in a case of acute voluntary massive arsenic intoxication resulting in severe rhabdomyolysis. The main features on muscle biopsy were perifascicular hypercontracted fibers, myofibrillar disruption, mitochondrial abnormalities and abundant cytoplasmic vacuoles containing lipids.","Acute arsenical myopathy: morphological descriptionAbs: We describe the histological findings of the muscle in a case of acute voluntary massive arsenic intoxication resulting in severe rhabdomyolysis. The main features on muscle biopsy were perifascicular hypercontracted fibers, myofibrillar disruption, mitochondrial abnormalities and abundant cytoplasmic vacuoles containing lipids."
57,Hanlon & Ferm 1986,Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis: 2 acute exposure," We have determined the concentration and chemical composition of arsenic in the blood of pregnant hamsters between 0.2 and 6 hr after an intraperitoneal injection of a teratogenic dose of radiolabeled sodium arsenate on the morning of the eighth day of gestation. Arsenic was present in plasma and red cells 0.20 hr postinjection. The plasma arsenic concentration reached a maximum of 220 mumole/kg blood near 0.5 hr postinjection. Plasma arsenic existed entirely as low-molecular-weight species. Both arsenite and dimethylarsinate (DMA) were present in plasma 0.20 hr postinjection, indicating that arsenate reduction and methylation of arsenic are rapidly initiated. However, the arsenite contribution remained small while the DMA contribution increased with time. Red cell arsenic included macromolecular arsenic (AsP) as well as three low-molecular-weight forms. The contribution of DMA remained small, but arsenite and AsP contributions increased with time. These findings identify the maternal blood concentration and chemical status of arsenic following the administration of a teratogenic dose of arsenate during the period of organogenesis. They could prove useful for predicting the likelihood of a teratogenic outcome in other mammalian species.","Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis: 2 acute exposureAbs: We have determined the concentration and chemical composition of arsenic in the blood of pregnant hamsters between 0.2 and 6 hr after an intraperitoneal injection of a teratogenic dose of radiolabeled sodium arsenate on the morning of the eighth day of gestation. Arsenic was present in plasma and red cells 0.20 hr postinjection. The plasma arsenic concentration reached a maximum of 220 mumole/kg blood near 0.5 hr postinjection. Plasma arsenic existed entirely as low-molecular-weight species. Both arsenite and dimethylarsinate (DMA) were present in plasma 0.20 hr postinjection, indicating that arsenate reduction and methylation of arsenic are rapidly initiated. However, the arsenite contribution remained small while the DMA contribution increased with time. Red cell arsenic included macromolecular arsenic (AsP) as well as three low-molecular-weight forms. The contribution of DMA remained small, but arsenite and AsP contributions increased with time. These findings identify the maternal blood concentration and chemical status of arsenic following the administration of a teratogenic dose of arsenate during the period of organogenesis. They could prove useful for predicting the likelihood of a teratogenic outcome in other mammalian species."
58,Kantor & Levin 1948,Arsenical encephalopathy in pregnancy with recovery,0,Arsenical encephalopathy in pregnancy with recoveryAbs:0
59,Klevay 1976,Pharmacology and toxicology of heavy metals: arsenic, ,Pharmacology and toxicology of heavy metals: arsenicAbs: 
60,Levin-Scherz et al. 1987,Acute arsenic ingestion," A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide. He died within 37 hours despite intensive treatment that included intramuscular dimercaprol and hemodialysis. Hemodynamic and laboratory data are presented illustrating the multisystem toxicities of inorganic arsenic. Hemodialysis, previously described as an effective therapeutic adjunct, was shown to be ineffective in this case.","Acute arsenic ingestionAbs: A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide. He died within 37 hours despite intensive treatment that included intramuscular dimercaprol and hemodialysis. Hemodynamic and laboratory data are presented illustrating the multisystem toxicities of inorganic arsenic. Hemodialysis, previously described as an effective therapeutic adjunct, was shown to be ineffective in this case."
61,Marafante et al. 1981,Intracellular interaction and metabolic fate of arsenite in the rabbit," Rabbits were treated with single doses of 50 micrograms AsO2-/kg b.w. by IP injection. At 48 h, 83.0 +/- 2.1% of arsenic is excreted via the urine. Also in blood the clearance of arsenic is rapid. Liver, kidney, and lung, among the tissues tested, show the highest concentration of arsenic at 5, 16, and 48 h after injection. Arsenic was found to be present at subcellular levels mainly in the nuclear and soluble fractions of the above-mentioned tissues. Chromatographic studies performed by gel filtration have shown that in plasma and in lung cytosol, arsenic is present, associated mainly to low molecular weight components, whereas in liver and kidney cytosol it is prevalently recovered in the fractions corresponding to the high molecular weight components. This different interaction of arsenic with molecular components was shown to influence the metabolic fate of this compound in the rabbit.","Intracellular interaction and metabolic fate of arsenite in the rabbitAbs: Rabbits were treated with single doses of 50 micrograms AsO2-/kg b.w. by IP injection. At 48 h, 83.0 +/- 2.1% of arsenic is excreted via the urine. Also in blood the clearance of arsenic is rapid. Liver, kidney, and lung, among the tissues tested, show the highest concentration of arsenic at 5, 16, and 48 h after injection. Arsenic was found to be present at subcellular levels mainly in the nuclear and soluble fractions of the above-mentioned tissues. Chromatographic studies performed by gel filtration have shown that in plasma and in lung cytosol, arsenic is present, associated mainly to low molecular weight components, whereas in liver and kidney cytosol it is prevalently recovered in the fractions corresponding to the high molecular weight components. This different interaction of arsenic with molecular components was shown to influence the metabolic fate of this compound in the rabbit."
62,Narang et al. 1987,Levels of arsenic in Indian opium eaters," Intake of opium is very common in India. The contraband material is generally contaminated with arsenic. Most often opium eaters present with neuropathy and hepatomegaly. Arsenic was estimated in serum, urine, nails and hair of opium eaters with and without neuropathy. Arsenic was also estimated in various opium samples. Arsenic was significantly higher in serum, urine, nails and hair of opium addicts when compared to controls. The opium samples analysed showed varyingly high amounts of arsenic.","Levels of arsenic in Indian opium eatersAbs: Intake of opium is very common in India. The contraband material is generally contaminated with arsenic. Most often opium eaters present with neuropathy and hepatomegaly. Arsenic was estimated in serum, urine, nails and hair of opium eaters with and without neuropathy. Arsenic was also estimated in various opium samples. Arsenic was significantly higher in serum, urine, nails and hair of opium addicts when compared to controls. The opium samples analysed showed varyingly high amounts of arsenic."
63,Pershagen & Bjorklund 1985,On the pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate in hamsters," The pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate was explored following 15 intratracheal instillations in male Syrian golden hamsters at weekly doses of about 3 mg/kg body weight (as arsenic). One lung adenoma appeared in 28 animals examined in the arsenic trisulfide group and 4 adenomas in 35 animals surviving the treatment with calcium arsenate. No adenomas were seen in 26 animals instilled with the vehicle (0.9% saline solution). The results show that calcium arsenate is tumorigenic (P less than 0.05), while the evidence is inconclusive for arsenic trisulfide.","On the pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate in hamstersAbs: The pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate was explored following 15 intratracheal instillations in male Syrian golden hamsters at weekly doses of about 3 mg/kg body weight (as arsenic). One lung adenoma appeared in 28 animals examined in the arsenic trisulfide group and 4 adenomas in 35 animals surviving the treatment with calcium arsenate. No adenomas were seen in 26 animals instilled with the vehicle (0.9% saline solution). The results show that calcium arsenate is tumorigenic (P less than 0.05), while the evidence is inconclusive for arsenic trisulfide."
64,Rezuke et al. 1991,Arsenic intoxication presenting as a myelodysplastic syndrome: a case report, A case of arsenic intoxication presenting as a myelodysplastic syndrome is reported. A 41-year-old woman with a 6-month history of gastrointestinal and neurological symptoms was noted to be pancytopenic at presentation. A bone marrow aspirate revealed dysmyelopoietic changes involving all three marrow cell lines. Subsequent analysis of urine for heavy metals demonstrated very high levels of arsenic. Treatment with British anti-Lewisite (BAL) resulted in the resolution of gastrointestinal symptoms and hematological abnormalities although the neurological complications progressed. This case emphasizes that heavy metal intoxication should be considered in the differential diagnosis of any individual presenting with the hematological features of myelodysplasia especially when accompanied by clinical features considered atypical for primary or secondary myelodysplasia.,Arsenic intoxication presenting as a myelodysplastic syndrome: a case reportAbs: A case of arsenic intoxication presenting as a myelodysplastic syndrome is reported. A 41-year-old woman with a 6-month history of gastrointestinal and neurological symptoms was noted to be pancytopenic at presentation. A bone marrow aspirate revealed dysmyelopoietic changes involving all three marrow cell lines. Subsequent analysis of urine for heavy metals demonstrated very high levels of arsenic. Treatment with British anti-Lewisite (BAL) resulted in the resolution of gastrointestinal symptoms and hematological abnormalities although the neurological complications progressed. This case emphasizes that heavy metal intoxication should be considered in the differential diagnosis of any individual presenting with the hematological features of myelodysplasia especially when accompanied by clinical features considered atypical for primary or secondary myelodysplasia.
65,Vahter et al. 1986,Airborne arsenic and urinary excretion of metabolites of inorganic arsenic among smelter workers," The relationship between airborne concentrations of arsenic and the urinary excretion of inorganic arsenic metabolites (inorganic arsenic + methylarsonic acid + dimethylarsinic acid) have been studied among smelter workers exposed to arsenic trioxide. The urinary concentrations of arsenic metabolites were found to increase steadily during the first day of the working week (after 2–3 d off from work), whereafter they reached a steady state. The concentration in the late evening after a day of exposure was very similar to that in the early morning after. Both were well correlated to the total daily excretion. In the second part of the study, comprising 18 subjects, the first-void morning urine of each participant was collected for 2 to 3 d during the steady-state phase. Total concentration of arsenic in the breathing zones was measured by personal air samplers. Airborne arsenic (8-h values) varied between 1 and 194 ug As/m3, and urinary arsenic between 16 and 328 ug As/g creatinine. With the urinary arsenic concentrations (mean values of 2–3 d for each subject) plotted against the corresponding airborne arsenic concentrations, the best fit was obtained by a power curve with the equation y = 17 x x^0.56. However, four of the participants were found to excrete far more (105–260%) arsenic in the urine than possibly could have been inhaled, most likely due to oral intake of arsenic via contaminated hands, cigarettes or snuff. If these four were excluded, the best fit was obtained by a straight regression line with the slope 2.0 and the intercept 29 ug As/g creatinine (coefficient of correlation 0.92; P < 0.001).","Airborne arsenic and urinary excretion of metabolites of inorganic arsenic among smelter workersAbs: The relationship between airborne concentrations of arsenic and the urinary excretion of inorganic arsenic metabolites (inorganic arsenic + methylarsonic acid + dimethylarsinic acid) have been studied among smelter workers exposed to arsenic trioxide. The urinary concentrations of arsenic metabolites were found to increase steadily during the first day of the working week (after 2–3 d off from work), whereafter they reached a steady state. The concentration in the late evening after a day of exposure was very similar to that in the early morning after. Both were well correlated to the total daily excretion. In the second part of the study, comprising 18 subjects, the first-void morning urine of each participant was collected for 2 to 3 d during the steady-state phase. Total concentration of arsenic in the breathing zones was measured by personal air samplers. Airborne arsenic (8-h values) varied between 1 and 194 ug As/m3, and urinary arsenic between 16 and 328 ug As/g creatinine. With the urinary arsenic concentrations (mean values of 2–3 d for each subject) plotted against the corresponding airborne arsenic concentrations, the best fit was obtained by a power curve with the equation y = 17 x x^0.56. However, four of the participants were found to excrete far more (105–260%) arsenic in the urine than possibly could have been inhaled, most likely due to oral intake of arsenic via contaminated hands, cigarettes or snuff. If these four were excluded, the best fit was obtained by a straight regression line with the slope 2.0 and the intercept 29 ug As/g creatinine (coefficient of correlation 0.92; P < 0.001)."
66,Webb et al. 1984,In vitro solubility and in vivo toxicity of gallium arsenide," The in vitro solubilities of gallium arsenide (GaAs) and its metal oxides were arsenic(III) oxide greater than GaAs much greater than gallium(III) oxide. GaAs dissolution was also dependent upon the type and concentration of buffer anion. The amount of arsenic dissolved in 12 hr by various aqueous media was 0.2 M phosphate buffer greater than or equal to 0.1 M phosphate buffer greater than Krebs-Hensleit buffer greater than distilled H2O greater than HCl-KCl buffer. GaAs was apparently soluble under in vivo conditions. Blood arsenic concentrations in rats 14 days after intratracheal instillation of 10, 30, or 100 mg/kg GaAs were 5.5, 14.3, and 53.6 micrograms/ml, respectively; gallium was not detected at any doses. An increase in lung wet weight at 14 days was dose dependent with these organs retaining 17 to 42% of the dose as gallium or arsenic. Excretion of gallium and arsenic was limited to the feces. Urinary porphyrin concentrations and body weight, monitored as indices of toxicity, were significantly altered over the 14-day study. The analysis of porphyrins revealed that uroporphyrin replaced coproporphyrin as the primary urinary metabolite. Rats receiving 10, 100, or 1000 mg/kg GaAs po exhibited similar signs of toxicity. Blood arsenic concentrations at 14 days were 3.5, 6.8, and 17.6 micrograms/ml, respectively. Porphyria was increased, and body weight was decreased at 1000 mg/kg GaAs. These values were equivalent to those obtained with an intratracheal dose of 10 to 30 mg/kg GaAs. Our results showed that pulmonary and po exposure to GaAs resulted in systemic arsenic intoxication. The finding that urinary uroporphyrin concentrations were greater than coproporphyrin concentrations may serve as a sensitive indicator for GaAs exposure.","In vitro solubility and in vivo toxicity of gallium arsenideAbs: The in vitro solubilities of gallium arsenide (GaAs) and its metal oxides were arsenic(III) oxide greater than GaAs much greater than gallium(III) oxide. GaAs dissolution was also dependent upon the type and concentration of buffer anion. The amount of arsenic dissolved in 12 hr by various aqueous media was 0.2 M phosphate buffer greater than or equal to 0.1 M phosphate buffer greater than Krebs-Hensleit buffer greater than distilled H2O greater than HCl-KCl buffer. GaAs was apparently soluble under in vivo conditions. Blood arsenic concentrations in rats 14 days after intratracheal instillation of 10, 30, or 100 mg/kg GaAs were 5.5, 14.3, and 53.6 micrograms/ml, respectively; gallium was not detected at any doses. An increase in lung wet weight at 14 days was dose dependent with these organs retaining 17 to 42% of the dose as gallium or arsenic. Excretion of gallium and arsenic was limited to the feces. Urinary porphyrin concentrations and body weight, monitored as indices of toxicity, were significantly altered over the 14-day study. The analysis of porphyrins revealed that uroporphyrin replaced coproporphyrin as the primary urinary metabolite. Rats receiving 10, 100, or 1000 mg/kg GaAs po exhibited similar signs of toxicity. Blood arsenic concentrations at 14 days were 3.5, 6.8, and 17.6 micrograms/ml, respectively. Porphyria was increased, and body weight was decreased at 1000 mg/kg GaAs. These values were equivalent to those obtained with an intratracheal dose of 10 to 30 mg/kg GaAs. Our results showed that pulmonary and po exposure to GaAs resulted in systemic arsenic intoxication. The finding that urinary uroporphyrin concentrations were greater than coproporphyrin concentrations may serve as a sensitive indicator for GaAs exposure."
67,Wojeck et al. 1982,Worker exposure to arsenic in Florida grapefruit spray operations," Dermal and respiratory exposures of arsenic (7440382) were measured in workers involved in mixing, loading, and applying lead-arsenate (301042) sprays to grapefruit trees. Five males from two citrus grower cooperatives participated in the study. Crew 1 consisted of one supplier who mixed the concentrated pesticides and filled the spray tank, and two applicators operating tractor drawn air blast sprayers. Applicators applied a 0.1 percent spray mixture of lead-arsenate at the rate of 4.7 kilograms active ingredient per hectare. Arsenic exposure was monitored for 9 days during the 5 week spray season. Crew 2 consisted of one supplier and one applicator. Arsenic exposure was monitored in a similar manner. Dermal exposure to hands was estimated from arsenic residues on gloves. Respirators with filter pads were used to assess respiratory exposure. Arsenic amounts were also detected in urine samples. For both groups, legs, feet, and hands received the highest percent of exposure. Applicator exposure was greater than supplier exposure for head, neck, back, chest, and arms. A comparison of the two groups showed that crew 2 had a 3:1 elevation in mean total body arsenic exposure. Suppliers had significantly greater arsenic excretion rates and concentrations than did applicators. The authors conclude that if spray material is more concentrated, a worker is correspondingly exposed to greater amounts of arsenic.","Worker exposure to arsenic in Florida grapefruit spray operationsAbs: Dermal and respiratory exposures of arsenic (7440382) were measured in workers involved in mixing, loading, and applying lead-arsenate (301042) sprays to grapefruit trees. Five males from two citrus grower cooperatives participated in the study. Crew 1 consisted of one supplier who mixed the concentrated pesticides and filled the spray tank, and two applicators operating tractor drawn air blast sprayers. Applicators applied a 0.1 percent spray mixture of lead-arsenate at the rate of 4.7 kilograms active ingredient per hectare. Arsenic exposure was monitored for 9 days during the 5 week spray season. Crew 2 consisted of one supplier and one applicator. Arsenic exposure was monitored in a similar manner. Dermal exposure to hands was estimated from arsenic residues on gloves. Respirators with filter pads were used to assess respiratory exposure. Arsenic amounts were also detected in urine samples. For both groups, legs, feet, and hands received the highest percent of exposure. Applicator exposure was greater than supplier exposure for head, neck, back, chest, and arms. A comparison of the two groups showed that crew 2 had a 3:1 elevation in mean total body arsenic exposure. Suppliers had significantly greater arsenic excretion rates and concentrations than did applicators. The authors conclude that if spray material is more concentrated, a worker is correspondingly exposed to greater amounts of arsenic."
68,Yamauchi et al. 1992,Metabolism of subcutaneous administered indium arsenide in the hamster," Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, but the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues.","Metabolism of subcutaneous administered indium arsenide in the hamsterAbs: Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, but the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues."
69,Clayton et al. 1999,"National human exposure assessment survey (NHEXAS): Distributions and associations of lead, arsenic, and volatile organic compounds in EPA Region 5"," The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 provides extensive exposure data on approximately 250 study participants selected via probability sampling. Associated environmental media and biomarker (blood, urine) concentration data were also obtained to aid in the understanding of relationships of the exposures to both contaminant sources and doses. Distributional parameters for arsenic (As), lead (Pb), and four volatile organic compounds (VOCs)--benzene, chloroform, tetrachloroethylene, and trichloroethylene--were estimated for each of the relevant media using weighted data analysis techniques. Inter-media associations were investigated through correlation analysis, and longitudinal correlations and models were used to investigate longitudinal patterns. Solid food appeared to be a major contributor to urine As levels, while Pb levels in household (HH) dust, personal air, and beverages all were significantly associated with blood Pb levels. Relatively high(>0.50) longitudinal correlations were observed for tap water Pb and As, as compared to only moderate longitudinal correlations for the personal air VOCs.","National human exposure assessment survey (NHEXAS): Distributions and associations of lead, arsenic, and volatile organic compounds in EPA Region 5Abs: The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 provides extensive exposure data on approximately 250 study participants selected via probability sampling. Associated environmental media and biomarker (blood, urine) concentration data were also obtained to aid in the understanding of relationships of the exposures to both contaminant sources and doses. Distributional parameters for arsenic (As), lead (Pb), and four volatile organic compounds (VOCs)--benzene, chloroform, tetrachloroethylene, and trichloroethylene--were estimated for each of the relevant media using weighted data analysis techniques. Inter-media associations were investigated through correlation analysis, and longitudinal correlations and models were used to investigate longitudinal patterns. Solid food appeared to be a major contributor to urine As levels, while Pb levels in household (HH) dust, personal air, and beverages all were significantly associated with blood Pb levels. Relatively high(>0.50) longitudinal correlations were observed for tap water Pb and As, as compared to only moderate longitudinal correlations for the personal air VOCs."
70,Tseng et al. 2000,Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan," Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index Greater/Equal to 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.","Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in TaiwanAbs: Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index Greater/Equal to 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings."
71,Calderon et al. 2001,Exposure to arsenic and lead and neuropsychological development in Mexican children," This cross-sectional study examined the effects of chronic exposure to lead (Pb), arsenic (AS) and undernutrition on the neuropsychological development of children. Two populations chronically exposed to either high (41 children) or low (39 children) levels of As and Pb were analyzed using the Wechsler Intelligence Scale for Children, Revised Version, for Mexico (WISC-RM). Geometric means of urinary arsenic (AsU) and lead in blood (PbB) were 62.9+/-0.03 (microgAs/g creatinine) and 8.9+/-0.03 (microg/dl) for the exposed group and 40.2+/-0.03 (microgAs/g creatinine) and 9.7+/-0.02 (microg/dl) for the reference group. The height for age index (HAI) was used as an indicator of chronic malnutrition and sociodemographic information was obtained with a questionnaire. Lead and arsenic were measured by atomic absorption spectrophotometry. Data on full, verbal, and performance intelligence quotients (IQ) scores, long-term memory, linguistic abstraction, attention span, and visuospatial organization were obtained through the WISC-RM. After controlling for significant potential confounders verbal IQ (P<0.01) decreased with increasing concentrations of AsU. The HAI correlated positively with full-scale and performance IQ (P<0.01). Higher levels of AsU were significantly related to poorer performance on WISC-RM factors examining long-term memory and linguistic abstraction, while lower scores in WISC-RM factors measuring attention were obtained at increasing values of PbB. Our results suggest that exposure to As and chronic malnutrition could have an influence on verbal abilities and long-term memory, while Pb exposure could affect the attention process even at low levels.","Exposure to arsenic and lead and neuropsychological development in Mexican childrenAbs: This cross-sectional study examined the effects of chronic exposure to lead (Pb), arsenic (AS) and undernutrition on the neuropsychological development of children. Two populations chronically exposed to either high (41 children) or low (39 children) levels of As and Pb were analyzed using the Wechsler Intelligence Scale for Children, Revised Version, for Mexico (WISC-RM). Geometric means of urinary arsenic (AsU) and lead in blood (PbB) were 62.9+/-0.03 (microgAs/g creatinine) and 8.9+/-0.03 (microg/dl) for the exposed group and 40.2+/-0.03 (microgAs/g creatinine) and 9.7+/-0.02 (microg/dl) for the reference group. The height for age index (HAI) was used as an indicator of chronic malnutrition and sociodemographic information was obtained with a questionnaire. Lead and arsenic were measured by atomic absorption spectrophotometry. Data on full, verbal, and performance intelligence quotients (IQ) scores, long-term memory, linguistic abstraction, attention span, and visuospatial organization were obtained through the WISC-RM. After controlling for significant potential confounders verbal IQ (P<0.01) decreased with increasing concentrations of AsU. The HAI correlated positively with full-scale and performance IQ (P<0.01). Higher levels of AsU were significantly related to poorer performance on WISC-RM factors examining long-term memory and linguistic abstraction, while lower scores in WISC-RM factors measuring attention were obtained at increasing values of PbB. Our results suggest that exposure to As and chronic malnutrition could have an influence on verbal abilities and long-term memory, while Pb exposure could affect the attention process even at low levels."
72,Spitzer et al. 1989,Chronic exposure to sour gas emissions: meeting a community concern with epidemiologic evidence," For 25 years residents of a rural area in southwestern Alberta have complained of health problems attributed to sour gas emissions from nearby natural gas refineries. We undertook a large epidemiologic study of the current health status and the selected morbidity rates among 2152 people in the exposed area. We established two comparison groups: one was a demographically similar unexposed population and the other a demographically different group also exposed to sour gas emissions in another region. The methods included a cross-sectional survey of current residents and separate historical cohort studies involving registry linkage to investigate cancer incidence and all-cause mortality. The cross-sectional survey involved a comprehensive health questionnaire, standardized clinical examinations by physicians blinded to the subjects' symptoms and concerns, and several laboratory tests. We were able to contact just under 60% of the people who we knew had moved from each area since 1958 and found no evidence of selective migration for health reasons. Although the residents of the exposed area reported an excess number of symptoms and health problems there were no significant differences in the mortality rate, incidence of cancer, reproductive problems, major ailments, hair levels of arsenic and certain metals or respiratory function between the groups.","Chronic exposure to sour gas emissions: meeting a community concern with epidemiologic evidenceAbs: For 25 years residents of a rural area in southwestern Alberta have complained of health problems attributed to sour gas emissions from nearby natural gas refineries. We undertook a large epidemiologic study of the current health status and the selected morbidity rates among 2152 people in the exposed area. We established two comparison groups: one was a demographically similar unexposed population and the other a demographically different group also exposed to sour gas emissions in another region. The methods included a cross-sectional survey of current residents and separate historical cohort studies involving registry linkage to investigate cancer incidence and all-cause mortality. The cross-sectional survey involved a comprehensive health questionnaire, standardized clinical examinations by physicians blinded to the subjects' symptoms and concerns, and several laboratory tests. We were able to contact just under 60% of the people who we knew had moved from each area since 1958 and found no evidence of selective migration for health reasons. Although the residents of the exposed area reported an excess number of symptoms and health problems there were no significant differences in the mortality rate, incidence of cancer, reproductive problems, major ailments, hair levels of arsenic and certain metals or respiratory function between the groups."
73,Mazumder et al. 2000,"Arsenic in drinking water and the prevalence of respiratory effects in West Bengal, India","<div>&nbsp;Background - A large population in West Bengal, India has been exposed to naturally occurring inorganic arsenic through their drinking water. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. The main focus of the study was skin keratoses and pigmentation alterations, two characteristic signs of ingested inorganic arsenic. Strong exposure-response gradients were found for these skin lesions. The study also collected limited information concerning respiratory system signs and symptoms, which we report here because increasing evidence suggests that arsenic ingestion also causes pulmonary effects. Methods - Participants were clinically examined and interviewed, and the arsenic content in their current primary drinking water source was measured. There were few smokers and analyses were confined to non-smokers (N = 6864 participants). Results - Among both males and females, the prevalence of cough, shortness of breath, and chest sounds (crepitations and/or rhonchi) in the lungs rose with increasing arsenic concentrations in drinking water. These respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesions. Prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic-induced skin lesions who also had high levels of arsenic in their current drinking water source (&lt;500 ug/l) compared with individuals who had normal skin and were exposed to low levels of arsenic (&gt;&lt;50 Ág/l). In participants with skin lesions, the age-adjusted POR estimates for cough were 7.8 for females (95% CI: 3.1-19.5) and 5.0 for males (95% CI: 2.6-9.9); for chest sounds POR for females was 9.6 (95% CI: 4.0-22.9) and for males 6.9 (95% CI: 3.1-15.0). The POR for shortness of breath in females was 23.2 (95% CI: 5.8-92.8) and in males 3.7 (95% CI: 1.3-10.6). Conclusion - These results add to evidence that long-term ingestion of inorganic arsenic can cause respiratory </div>","Arsenic in drinking water and the prevalence of respiratory effects in West Bengal, IndiaAbs:<div>&nbsp;Background - A large population in West Bengal, India has been exposed to naturally occurring inorganic arsenic through their drinking water. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. The main focus of the study was skin keratoses and pigmentation alterations, two characteristic signs of ingested inorganic arsenic. Strong exposure-response gradients were found for these skin lesions. The study also collected limited information concerning respiratory system signs and symptoms, which we report here because increasing evidence suggests that arsenic ingestion also causes pulmonary effects. Methods - Participants were clinically examined and interviewed, and the arsenic content in their current primary drinking water source was measured. There were few smokers and analyses were confined to non-smokers (N = 6864 participants). Results - Among both males and females, the prevalence of cough, shortness of breath, and chest sounds (crepitations and/or rhonchi) in the lungs rose with increasing arsenic concentrations in drinking water. These respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesions. Prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic-induced skin lesions who also had high levels of arsenic in their current drinking water source (&lt;500 ug/l) compared with individuals who had normal skin and were exposed to low levels of arsenic (&gt;&lt;50 Ág/l). In participants with skin lesions, the age-adjusted POR estimates for cough were 7.8 for females (95% CI: 3.1-19.5) and 5.0 for males (95% CI: 2.6-9.9); for chest sounds POR for females was 9.6 (95% CI: 4.0-22.9) and for males 6.9 (95% CI: 3.1-15.0). The POR for shortness of breath in females was 23.2 (95% CI: 5.8-92.8) and in males 3.7 (95% CI: 1.3-10.6). Conclusion - These results add to evidence that long-term ingestion of inorganic arsenic can cause respiratory </div>"
74,Murphy et al. 1989,Health risk assessment for arsenic contaminated soil," BIOSIS COPYRIGHT: BIOL ABS. This paper describes risk assessment methods for two chronic exposure pathways involving arsenic contaminated soil, namely inhalation of fugitive dust emissions over a lifetime, and inadvertent soil/house dust ingestion. The endpoint in the first case is assumed to be lung cancer and in the second case skin cancer. In order to estimate exposures, inhalation rates and soil/dust ingestion rates are estimated for different age groups; indoor/outdoor time budgets for different age groups are developed; and indoor surface dust and air arsenic concentrations are estimated based on outdoor concentration measurements. Differences observed in indoor/outdoor ratios and arsenic containing dust particle size among different types of communities are noted, as well as possible relationship of particle size to bioavailability. Calculations of risk are presented using cancer potency factors developed by the U.S. Environmental Protection Agency, and uncertainties in these toxicity estima","Health risk assessment for arsenic contaminated soilAbs: BIOSIS COPYRIGHT: BIOL ABS. This paper describes risk assessment methods for two chronic exposure pathways involving arsenic contaminated soil, namely inhalation of fugitive dust emissions over a lifetime, and inadvertent soil/house dust ingestion. The endpoint in the first case is assumed to be lung cancer and in the second case skin cancer. In order to estimate exposures, inhalation rates and soil/dust ingestion rates are estimated for different age groups; indoor/outdoor time budgets for different age groups are developed; and indoor surface dust and air arsenic concentrations are estimated based on outdoor concentration measurements. Differences observed in indoor/outdoor ratios and arsenic containing dust particle size among different types of communities are noted, as well as possible relationship of particle size to bioavailability. Calculations of risk are presented using cancer potency factors developed by the U.S. Environmental Protection Agency, and uncertainties in these toxicity estima"
75,Wallace 1991,Comparison of risks from outdoor and indoor exposure to toxic chemicals," Environmental Protection Agency TEAM (Total Exposure Assessment Measurement) Studies have measured exposures of about 800 persons to 25 volatile organic compounds (VOCs) and exposures of about 300 persons to 32 pesticides. These persons were selected to represent more than 1 million residents of industrial manufacturing cities such as Bayonne and Elizabeth, New Jersey, and Los Angeles, California; cities with light industry, such as Greensboro, North Carolina, and Baltimore, Maryland; rural areas such as Devils Lake, North Dakota; and cities with high pesticide use such as Jacksonville, Florida, as well as low-to-moderate pesticide use such as Springfield, Massachusetts. The TEAM data provide an opportunity to estimate the risks from airborne exposure to a number of suspected carcinogens for a substantial number of persons residing in a wide variety of urban, suburban, and rural areas. Because all of the TEAM Studies measured outdoor concentrations near the homes of the participants, it is possible to apportion the risks between outdoor and indoor sources. Upper-bound lifetime risks of cancer are calculated for both indoor and outdoor sources of 12 VOCs and about 23 pesticides measured in the TEAM Studies. These risk calculations are supplemented by calculations based on other studies for some additional pollutants, including radon and environmental tobacco smoke. The relationship of these upper-bound risk estimates to ""best-guess"" values is discussed. Sharper estimates of risk based on identifying population subgroups exposed to major sources are also discussed. Important gaps in our knowledge of exposure measurements are identified, e.g., particulates (including polyaromatic hydrocarbons); 1,3-butadiene, asbestos, chromium, cadmium, arsenic, vinyl chloride, methylene chloride, and most polar organics.","Comparison of risks from outdoor and indoor exposure to toxic chemicalsAbs: Environmental Protection Agency TEAM (Total Exposure Assessment Measurement) Studies have measured exposures of about 800 persons to 25 volatile organic compounds (VOCs) and exposures of about 300 persons to 32 pesticides. These persons were selected to represent more than 1 million residents of industrial manufacturing cities such as Bayonne and Elizabeth, New Jersey, and Los Angeles, California; cities with light industry, such as Greensboro, North Carolina, and Baltimore, Maryland; rural areas such as Devils Lake, North Dakota; and cities with high pesticide use such as Jacksonville, Florida, as well as low-to-moderate pesticide use such as Springfield, Massachusetts. The TEAM data provide an opportunity to estimate the risks from airborne exposure to a number of suspected carcinogens for a substantial number of persons residing in a wide variety of urban, suburban, and rural areas. Because all of the TEAM Studies measured outdoor concentrations near the homes of the participants, it is possible to apportion the risks between outdoor and indoor sources. Upper-bound lifetime risks of cancer are calculated for both indoor and outdoor sources of 12 VOCs and about 23 pesticides measured in the TEAM Studies. These risk calculations are supplemented by calculations based on other studies for some additional pollutants, including radon and environmental tobacco smoke. The relationship of these upper-bound risk estimates to ""best-guess"" values is discussed. Sharper estimates of risk based on identifying population subgroups exposed to major sources are also discussed. Important gaps in our knowledge of exposure measurements are identified, e.g., particulates (including polyaromatic hydrocarbons); 1,3-butadiene, asbestos, chromium, cadmium, arsenic, vinyl chloride, methylene chloride, and most polar organics."
76,Baker et al. 1990,Environmentally related disorders of the nervous system," Specific physical and chemical agents found in the workplace and in the general environment are responsible for characteristic pathologic processes within the nervous system. It has been shown that many neurotoxic agents produce a dose-related spectrum of impairment ranging from mild slowing of nerve conducting velocity or prolongation in reaction time to neuropathy and frank encephalopathy. Clinical manifestations are determined by the agent involved, by the dose of exposure, the vulnerability of the cellular target, the ability of the organism to metabolize and excrete the agent, and the ability to repair damage. An occupational history, including evaluation of evidence of specific agents and job history, is a critical component in the clinical management of individuals with suspect neurotoxic disease. Environmentally-induced disorders can be prevented by appropriate environmental controls. Prevention of neurotoxic disease is a complex process requiring continuous involvement of public health agencies and strong scientific research.","Environmentally related disorders of the nervous systemAbs: Specific physical and chemical agents found in the workplace and in the general environment are responsible for characteristic pathologic processes within the nervous system. It has been shown that many neurotoxic agents produce a dose-related spectrum of impairment ranging from mild slowing of nerve conducting velocity or prolongation in reaction time to neuropathy and frank encephalopathy. Clinical manifestations are determined by the agent involved, by the dose of exposure, the vulnerability of the cellular target, the ability of the organism to metabolize and excrete the agent, and the ability to repair damage. An occupational history, including evaluation of evidence of specific agents and job history, is a critical component in the clinical management of individuals with suspect neurotoxic disease. Environmentally-induced disorders can be prevented by appropriate environmental controls. Prevention of neurotoxic disease is a complex process requiring continuous involvement of public health agencies and strong scientific research."
77,Colt et al. 2002,Sampling private wells at past homes to estimate arsenic exposure: a methodologic study in New England," We are conducting a collaborative, population-based case-control study in Maine. New Hampshire. and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three - state study area of Maine, New Hampshire. and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all. 48(47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located 22%) or had been demolished (2%),permission to sample the wells was not obtained (17%). the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling Water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible. Journal of Exposure Analysis and Environmental Epidemiology (2002) 12, 329-334 doi:10. 1038/sj.jea.7500235Keywords: arsenic, drinking water, exposure assessment, private wells.","Sampling private wells at past homes to estimate arsenic exposure: a methodologic study in New EnglandAbs: We are conducting a collaborative, population-based case-control study in Maine. New Hampshire. and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three - state study area of Maine, New Hampshire. and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all. 48(47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located 22%) or had been demolished (2%),permission to sample the wells was not obtained (17%). the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling Water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible. Journal of Exposure Analysis and Environmental Epidemiology (2002) 12, 329-334 doi:10. 1038/sj.jea.7500235Keywords: arsenic, drinking water, exposure assessment, private wells."
78,Karagas et al. 1998,Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U S population," Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic.","Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U S populationAbs: Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic."
79,Pellizzari et al. 1995,Population-based exposure measurements in EPA region 5: a phase I field study in support of the national human exposure assessment survey," The National Human Exposure Assessment Survey (NHEXAS) Phase I study is designed to be part of the total NHEXAS framework developed from a series of scientific discussions and workshops conducted by the U.S. Environmental Protection Agency (EPA) during 1992 and 1993. NHEXAS examines total human exposure and is structured to include: Phase I, scoping studies; Phase II, a full national exposure survey; and Phase III, a series of highly focused characterization modules. Our research program examines the scientific issues important to Phase II, including statistical sampling, methods evaluation, media concentration measurements, formulating quality assurance goals, and identification of important pathways leading to exposure. To determine the feasibility of NHEXAS in characterizing human exposure for a representative population, a hypothesis-driven design is used to answer important questions about human exposure to specific environmental contaminants. This paper describes: (1) hypotheses to be tested; (2) contaminants selected for study; (3) strategies for measuring exposure; (4) study area and population; (5) population sampling design; (6) media sampling and analysis procedures; and (7) data analysis. The contaminants of concern in this Phase I study include selected metals and volatile organic compounds. From these classes the first-tier contaminants to be measured are lead, arsenic, benzene, chloroform, perchloroethylene, and trichloroethylene. Contaminants selected for examination may potentially be found in many media (personal-nonoccupational, personal-occupational, indoor, and outdoor residential air; dust; potable water; food/beverages; soil; blood; hair; and urine) and exposures may occur by multiple routes (inhalation, ingestion, dermal). The central hypothesis of our field study is to discover whether individual and population exposures determined by modeled or extant data are/are not significantly different from those determined directly from multipathway and multimedia measurements. In addition, there are a series of subhypotheses ranging from pollutant-specific exposure measurement and body burden hypotheses to the optimization of exposure models. In keeping with the NHEXAS framework, a probability-based population sample for total exposure and the field study will be conducted in counties located throughout EPA Region 5 (Minnesota, Wisconsin, Illinois, Indiana, Ohio, and Michigan). Sampling units will be households and an individual residing within each household. Environmental, exposure, and biological media sample collection will be performed by this consortium. Analyses of the external media and biological media samples will be completed by this consortium or Federal laboratories of the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), or EPA. The protocols and analytical techniques selected for use represent the best available for total exposure assessment at this time.","Population-based exposure measurements in EPA region 5: a phase I field study in support of the national human exposure assessment surveyAbs: The National Human Exposure Assessment Survey (NHEXAS) Phase I study is designed to be part of the total NHEXAS framework developed from a series of scientific discussions and workshops conducted by the U.S. Environmental Protection Agency (EPA) during 1992 and 1993. NHEXAS examines total human exposure and is structured to include: Phase I, scoping studies; Phase II, a full national exposure survey; and Phase III, a series of highly focused characterization modules. Our research program examines the scientific issues important to Phase II, including statistical sampling, methods evaluation, media concentration measurements, formulating quality assurance goals, and identification of important pathways leading to exposure. To determine the feasibility of NHEXAS in characterizing human exposure for a representative population, a hypothesis-driven design is used to answer important questions about human exposure to specific environmental contaminants. This paper describes: (1) hypotheses to be tested; (2) contaminants selected for study; (3) strategies for measuring exposure; (4) study area and population; (5) population sampling design; (6) media sampling and analysis procedures; and (7) data analysis. The contaminants of concern in this Phase I study include selected metals and volatile organic compounds. From these classes the first-tier contaminants to be measured are lead, arsenic, benzene, chloroform, perchloroethylene, and trichloroethylene. Contaminants selected for examination may potentially be found in many media (personal-nonoccupational, personal-occupational, indoor, and outdoor residential air; dust; potable water; food/beverages; soil; blood; hair; and urine) and exposures may occur by multiple routes (inhalation, ingestion, dermal). The central hypothesis of our field study is to discover whether individual and population exposures determined by modeled or extant data are/are not significantly different from those determined directly from multipathway and multimedia measurements. In addition, there are a series of subhypotheses ranging from pollutant-specific exposure measurement and body burden hypotheses to the optimization of exposure models. In keeping with the NHEXAS framework, a probability-based population sample for total exposure and the field study will be conducted in counties located throughout EPA Region 5 (Minnesota, Wisconsin, Illinois, Indiana, Ohio, and Michigan). Sampling units will be households and an individual residing within each household. Environmental, exposure, and biological media sample collection will be performed by this consortium. Analyses of the external media and biological media samples will be completed by this consortium or Federal laboratories of the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), or EPA. The protocols and analytical techniques selected for use represent the best available for total exposure assessment at this time."
80,Wolfsperger et al. 1994,Heavy metals in human hair samples from Austria and Italy: influence of sex and smoking habits," Hair samples from 79 young healthy adults from Vienna (Austria) and Rome (Italy) were analyzed for As, Cd, Co, Cr, Ni and Pb by ICP-MS. No differences were found between the two locations except for chromium, which was significantly higher in the Viennese population (P &lt; 0.001). In both cities male hair contained higher arsenic (P &lt; 0.001) and lower cadmium (P &lt; 0.05) levels than female hair, and in Vienna lead concentrations were lower in males (P &lt; 0.05). Striking differences appeared when smokers were compared with non-smokers. Geometric means (micrograms/g) of smokers versus non-smokers were: arsenic 0.081 vs. 0.065, cadmium 0.075 vs. 0.038 (P &lt; 0.05), cobalt 0.025 vs. 0.010 (P &lt; 0.05), chromium 0.84 vs. 0.72 (P &lt; 0.05), lead 3.42 vs. 1.47 (P &lt; 0.001) and nickel 0.64 vs. 0.32 (P &lt; 0.005). Consideration of a large number of biological and behavioural factors minimizes bias inherent in unmatched sample composition.","Heavy metals in human hair samples from Austria and Italy: influence of sex and smoking habitsAbs: Hair samples from 79 young healthy adults from Vienna (Austria) and Rome (Italy) were analyzed for As, Cd, Co, Cr, Ni and Pb by ICP-MS. No differences were found between the two locations except for chromium, which was significantly higher in the Viennese population (P &lt; 0.001). In both cities male hair contained higher arsenic (P &lt; 0.001) and lower cadmium (P &lt; 0.05) levels than female hair, and in Vienna lead concentrations were lower in males (P &lt; 0.05). Striking differences appeared when smokers were compared with non-smokers. Geometric means (micrograms/g) of smokers versus non-smokers were: arsenic 0.081 vs. 0.065, cadmium 0.075 vs. 0.038 (P &lt; 0.05), cobalt 0.025 vs. 0.010 (P &lt; 0.05), chromium 0.84 vs. 0.72 (P &lt; 0.05), lead 3.42 vs. 1.47 (P &lt; 0.001) and nickel 0.64 vs. 0.32 (P &lt; 0.005). Consideration of a large number of biological and behavioural factors minimizes bias inherent in unmatched sample composition."
81,Savitz et al. 1989,"Effect of parents' occupational exposures on risk of stillbirth, preterm delivery, and small-for-gestational-age infants", BIOSIS COPYRIGHT: BIOL ABS. RRM HUMAN POLYVINYL ALCOHOL RUBBER PLASTIC LEAD SYNTHETICS GLASS CLAY STONE TEXTILE MINING INDUSTRIES X-RAYS STATISTICS,"Effect of parents' occupational exposures on risk of stillbirth, preterm delivery, and small-for-gestational-age infantsAbs: BIOSIS COPYRIGHT: BIOL ABS. RRM HUMAN POLYVINYL ALCOHOL RUBBER PLASTIC LEAD SYNTHETICS GLASS CLAY STONE TEXTILE MINING INDUSTRIES X-RAYS STATISTICS"
82,Mitchell-Heggs et al. 1990,Herbal medicine as a cause of combined lead and arsenic poisoning," 1. Combined chronic lead and arsenic poisoning was diagnosed in a 33-year-old Korean woman following consumption of a Korean herbal medicine prescribed for haemorrhoids. 2. The patient had malaise, severe difficulty walking, arthralgia, oedema and abdominal pain with diarrhoea. 3. Investigation showed anaemia with basophilic stippling, fragmentation and a raised reticulocyte count. 4. Raised blood and urine lead levels and urine arsenic levels were found. 5. Analysis of the herbal medicine revealed a high lead and arsenic content. 6. Treatment with the newer chelating agent 2,3-dimercaptosuccinic acid was successful, with no detectable side-effects.","Herbal medicine as a cause of combined lead and arsenic poisoningAbs: 1. Combined chronic lead and arsenic poisoning was diagnosed in a 33-year-old Korean woman following consumption of a Korean herbal medicine prescribed for haemorrhoids. 2. The patient had malaise, severe difficulty walking, arthralgia, oedema and abdominal pain with diarrhoea. 3. Investigation showed anaemia with basophilic stippling, fragmentation and a raised reticulocyte count. 4. Raised blood and urine lead levels and urine arsenic levels were found. 5. Analysis of the herbal medicine revealed a high lead and arsenic content. 6. Treatment with the newer chelating agent 2,3-dimercaptosuccinic acid was successful, with no detectable side-effects."
83,Anger 1990,Worksite behavioral research results: sensitive methods test batteries and the transition from laboratory data to human health," BIOSIS COPYRIGHT: BIOL ABS. Ample evidence demonstrates that many chemicals, at some concentration, affect the nervous system. Disastrous incidents resulting from food adulteration, medical experiments and pharmaceutical errors, and industrial and environmental exposures warn of the serious potential for neurotoxicants to affect human health. This article identifies the approximately 185 epidemiological behavioral neurotoxicology studies published through 1989 of extended workplace exposures to chemicals. Approximately 250 different tests have been administered to exposed workers in primarily cross sectional studies, and statistically significant decrements were reported in 43% of the approximately 1100 test/population administrations (virtually all 185 studies employed several of the 250 tests). In this research, 28 different chemicals as well as multiple chemical exposures have been studied. The most extensive findings are seen in research on carbon disulfide, lead, mercury, and multiple solvent","Worksite behavioral research results: sensitive methods test batteries and the transition from laboratory data to human healthAbs: BIOSIS COPYRIGHT: BIOL ABS. Ample evidence demonstrates that many chemicals, at some concentration, affect the nervous system. Disastrous incidents resulting from food adulteration, medical experiments and pharmaceutical errors, and industrial and environmental exposures warn of the serious potential for neurotoxicants to affect human health. This article identifies the approximately 185 epidemiological behavioral neurotoxicology studies published through 1989 of extended workplace exposures to chemicals. Approximately 250 different tests have been administered to exposed workers in primarily cross sectional studies, and statistically significant decrements were reported in 43% of the approximately 1100 test/population administrations (virtually all 185 studies employed several of the 250 tests). In this research, 28 different chemicals as well as multiple chemical exposures have been studied. The most extensive findings are seen in research on carbon disulfide, lead, mercury, and multiple solvent"
84,Gift et al. 1991,Biological markers: monitoring populations exposed to hazardous substances," The use and need for biological markers for monitoring exposure to hazardous substances were discussed. A biological marker was defined as any exogenous substance or metabolite or the product of an interaction between a xenobiotic and some target molecule that can be detected within an organism. The uses of biological markers were illustrated through 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) and lead (7439921) as examples. The historical background of laboratory testing to detect exposure to hazardous agents was outlined. Consideration was also given to problems with using exposure markers and biological markers of effect. The latter were defined as any measurable biochemical, physiological, or other change that, depending on its magnitude, can be recognized as a health impairment or disease. Examples of Agency for Toxic Substances and Disease Registry pilot exposure studies that utilized biological effect markers were summarized. These included studies of the effects of arsenic (7440382), lead, polychlorinated biphenyls, TCDD, pesticides, and volatile organic compounds. Problems with using biological markers of effect and validation of biological markers were discussed. Future directions for biological marker research were indicated.","Biological markers: monitoring populations exposed to hazardous substancesAbs: The use and need for biological markers for monitoring exposure to hazardous substances were discussed. A biological marker was defined as any exogenous substance or metabolite or the product of an interaction between a xenobiotic and some target molecule that can be detected within an organism. The uses of biological markers were illustrated through 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) and lead (7439921) as examples. The historical background of laboratory testing to detect exposure to hazardous agents was outlined. Consideration was also given to problems with using exposure markers and biological markers of effect. The latter were defined as any measurable biochemical, physiological, or other change that, depending on its magnitude, can be recognized as a health impairment or disease. Examples of Agency for Toxic Substances and Disease Registry pilot exposure studies that utilized biological effect markers were summarized. These included studies of the effects of arsenic (7440382), lead, polychlorinated biphenyls, TCDD, pesticides, and volatile organic compounds. Problems with using biological markers of effect and validation of biological markers were discussed. Future directions for biological marker research were indicated."
85,Rastogi et al. 1991,A cross-sectional study of pulmonary function among workers exposed to multimetals in the glass bangle industry," Spirometric lung functions were evaluated in 220 asymptomatic glass bangle workers exposed to the salts of various heavy metals, such as arsenic, lead, zinc, copper, manganese, cobalt, cadmium, and selenium, which are used as coloring agents in the manufacture of glass bangles. The mean values of various spirometric variables (viz. FVC, FEV1, IMBC, and PEFR) were within normal range (more than 80% of the predicted values) in both smoking and nonsmoking glass bangle workers and did not reveal any significant differences in comparison with those observed in the unexposed controls. However, variables such as FEV1/FVC% ratio, FEF25-75 and FEF75-85 were reduced significantly (p less than 0.001) in the exposed group. The reduction was more marked in the smoking glass bangle workers indicating additive effect of cigarette smoking on the small airways. The exposed group showed a significantly higher prevalence (16.3%) of respiratory impairment in comparison to that observed in the controls (7.9%) as a result of exposure to various metals in the work environment (p less than 0.01). The respiratory impairment observed in the exposed group indicated primarily restrictive pattern of pulmonary abnormality (10.4%), while the controls revealed only 1.1% prevalence of this disease (p less than 0.001). The effect of the duration of exposure on the prevalence of respiratory impairment in the glass bangle industry revealed significantly higher prevalence (p less than 0.05) in those who worked for more than 10 years (23.0%) than in those who worked for less than 10 years (10.8%) thereby indicating that the duration of exposure is directly related to the prevalence of respiratory impairment.","A cross-sectional study of pulmonary function among workers exposed to multimetals in the glass bangle industryAbs: Spirometric lung functions were evaluated in 220 asymptomatic glass bangle workers exposed to the salts of various heavy metals, such as arsenic, lead, zinc, copper, manganese, cobalt, cadmium, and selenium, which are used as coloring agents in the manufacture of glass bangles. The mean values of various spirometric variables (viz. FVC, FEV1, IMBC, and PEFR) were within normal range (more than 80% of the predicted values) in both smoking and nonsmoking glass bangle workers and did not reveal any significant differences in comparison with those observed in the unexposed controls. However, variables such as FEV1/FVC% ratio, FEF25-75 and FEF75-85 were reduced significantly (p less than 0.001) in the exposed group. The reduction was more marked in the smoking glass bangle workers indicating additive effect of cigarette smoking on the small airways. The exposed group showed a significantly higher prevalence (16.3%) of respiratory impairment in comparison to that observed in the controls (7.9%) as a result of exposure to various metals in the work environment (p less than 0.01). The respiratory impairment observed in the exposed group indicated primarily restrictive pattern of pulmonary abnormality (10.4%), while the controls revealed only 1.1% prevalence of this disease (p less than 0.001). The effect of the duration of exposure on the prevalence of respiratory impairment in the glass bangle industry revealed significantly higher prevalence (p less than 0.05) in those who worked for more than 10 years (23.0%) than in those who worked for less than 10 years (10.8%) thereby indicating that the duration of exposure is directly related to the prevalence of respiratory impairment."
86,Willers et al. 1992,"Exposure to environmental tobacco smoke in the household and urinary cotinine excretion, heavy metals retention, and lung function"," The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U-As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U-cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children.","Exposure to environmental tobacco smoke in the household and urinary cotinine excretion, heavy metals retention, and lung functionAbs: The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U-As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U-cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children."
87,Steenland et al. 1992,The mortality of lead smelter workers: an update," A followup study was conducted on the mortality rates of a group of lead (7439921) smelter workers which had been studied from 1977 through 1988. The average airborne lead concentration to which these workers had been exposed was 3.1mg/m3 and the blood levels averaged 56.3 micrograms/100 milliliters in 1976. Arsenic (7440382) exposures in this cohort were relatively low. An excess amount of kidney cancer was identified in the group, particularly at the higher exposure levels. A previously elevated rate of chronic renal disease was lessened somewhat in this followup period. Deaths from accidents and nonmalignant respiratory disease were significantly increased. When comparing the findings based on length of exposure, chronic renal disease was elevated among those with the longest exposure histories. No specific trend was noted for kidney cancer with regard either to duration of exposure or time since first exposure.","The mortality of lead smelter workers: an updateAbs: A followup study was conducted on the mortality rates of a group of lead (7439921) smelter workers which had been studied from 1977 through 1988. The average airborne lead concentration to which these workers had been exposed was 3.1mg/m3 and the blood levels averaged 56.3 micrograms/100 milliliters in 1976. Arsenic (7440382) exposures in this cohort were relatively low. An excess amount of kidney cancer was identified in the group, particularly at the higher exposure levels. A previously elevated rate of chronic renal disease was lessened somewhat in this followup period. Deaths from accidents and nonmalignant respiratory disease were significantly increased. When comparing the findings based on length of exposure, chronic renal disease was elevated among those with the longest exposure histories. No specific trend was noted for kidney cancer with regard either to duration of exposure or time since first exposure."
88,Markowitz et al. 1994,Lead poisoning due to hai ge fen: the porphyrin content of individual erythrocytes," A 45-year-old Korean man developed abdominal colic, muscle pain, and fatigue. Following a 3-week hospitalization, acute intermittent porphyria was diagnosed based on the symptoms and a high level of urinary delta-aminolevulinic acid (378 mumol/L [4.95 mg/dL]). However, discovery of an elevated blood lead level (3.7 mumol/L [76 micrograms/dL]) subsequently led to the correct diagnosis. No occupational source of lead exposure was identified. The patient reported ingesting a Chinese herbal preparation for 4 weeks prior to becoming ill. A public health investigation revealed that the source of lead exposure was hai ge fen (clamshell powder), one of the 36 ingredients of the Chinese herbal medicine. We used fluorescence image-based cytometry to determine the frequency distribution of the zinc protoporphyrin content in circulating red blood cells and found that 70% of the patient's cells contained elevated levels of zinc protoporphyrin, consistent with the duration of lead exposure and effect of lead on heme synthesis. Analysis of zinc protoporphyrin content in circulating red blood cell distributions may be useful in the diagnosis, therapy, and kinetic modeling of lead poisoning. Environmental lead poisoning is best addressed through the close collaboration of clinicians, public health specialists, and laboratory scientists.","Lead poisoning due to hai ge fen: the porphyrin content of individual erythrocytesAbs: A 45-year-old Korean man developed abdominal colic, muscle pain, and fatigue. Following a 3-week hospitalization, acute intermittent porphyria was diagnosed based on the symptoms and a high level of urinary delta-aminolevulinic acid (378 mumol/L [4.95 mg/dL]). However, discovery of an elevated blood lead level (3.7 mumol/L [76 micrograms/dL]) subsequently led to the correct diagnosis. No occupational source of lead exposure was identified. The patient reported ingesting a Chinese herbal preparation for 4 weeks prior to becoming ill. A public health investigation revealed that the source of lead exposure was hai ge fen (clamshell powder), one of the 36 ingredients of the Chinese herbal medicine. We used fluorescence image-based cytometry to determine the frequency distribution of the zinc protoporphyrin content in circulating red blood cells and found that 70% of the patient's cells contained elevated levels of zinc protoporphyrin, consistent with the duration of lead exposure and effect of lead on heme synthesis. Analysis of zinc protoporphyrin content in circulating red blood cell distributions may be useful in the diagnosis, therapy, and kinetic modeling of lead poisoning. Environmental lead poisoning is best addressed through the close collaboration of clinicians, public health specialists, and laboratory scientists."
89,Gerhardt et al. 1980,Trace element content of moonshine," Although the contamination of illicit whiskey with lead is widely accepted, the potential for exposure to other trace elements from drinking &quot;moonshine&quot; is less well appreciated. To better understand the potential for trace element poisoning, we undertook an analysis of samples of Georgia moonshine. Although a number of elements were not found in significant quantities to be considered harmful, four elements (copper, zinc, lead, and arsenic) were present in potentially toxic concentrations. The possible implications and sources of the contamination are discussed.","Trace element content of moonshineAbs: Although the contamination of illicit whiskey with lead is widely accepted, the potential for exposure to other trace elements from drinking &quot;moonshine&quot; is less well appreciated. To better understand the potential for trace element poisoning, we undertook an analysis of samples of Georgia moonshine. Although a number of elements were not found in significant quantities to be considered harmful, four elements (copper, zinc, lead, and arsenic) were present in potentially toxic concentrations. The possible implications and sources of the contamination are discussed."
90,Stayner et al. 2003,Attenuation of exposure-response curves in occupational cohort studies at high exposure levels," Numerous occupational cohort mortality studies have observed exposure-response curves to have an increasing slope at low exposure levels that attenuates or even turns negative at high exposure levels. Examples discussed in this paper include dioxin, silica, 1 ,3-butadiene, cadmium, beryllium, radon daughters, diesel fumes, nickel, arsenic, and hexavalent chromium. Possible explanations for this phenomenon include (i) bias introduced by the healthy worker survivor effect, (ii) a depletion of the number of susceptible people in the population at high exposure levels, (iii) a natural limit on the relative risk for diseases with a high background rate, (iv) mismeasurement or misclassification of exposures, (v) the influence of other risk factors that vary by the level of the main exposure, and (vi) the saturation of key enzyme systems or other processes involved in the development of disease.","Attenuation of exposure-response curves in occupational cohort studies at high exposure levelsAbs: Numerous occupational cohort mortality studies have observed exposure-response curves to have an increasing slope at low exposure levels that attenuates or even turns negative at high exposure levels. Examples discussed in this paper include dioxin, silica, 1 ,3-butadiene, cadmium, beryllium, radon daughters, diesel fumes, nickel, arsenic, and hexavalent chromium. Possible explanations for this phenomenon include (i) bias introduced by the healthy worker survivor effect, (ii) a depletion of the number of susceptible people in the population at high exposure levels, (iii) a natural limit on the relative risk for diseases with a high background rate, (iv) mismeasurement or misclassification of exposures, (v) the influence of other risk factors that vary by the level of the main exposure, and (vi) the saturation of key enzyme systems or other processes involved in the development of disease."
91,Llobet et al. 1998,"Biological monitoring of environmental pollution and human exposure to metals in Tarragona, Spain III Blood levels"," Blood samples were obtained from 72 men and 72 women (age > 16 years) living in 3 residential areas in the vicinity of a new hazardous waste incinerator (HWI), now under construction (Tarragona, Spain). The samples were subjected to arsenic (As), beryllium (Be), cadmium (Cd),chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (TI), and vanadium (V) analyses. Beryllium, Cd, Cr, Mn, Ni, Pb, Tl, Sn, and V were measured by ICP-MS. Arsenic and Hg were determined by using hydride generation/ICP-MS. Results were analyzed in terms of age, sex, and specific place of residence. Arsenic, Be, TI, and V levels were under the respective detection limits. The geometric mean concentrations and ranges ( g/dl) of the remaining elements were the following: Cd 0.70 (0.20-3.24), Cr 0.02 (0.01 -0.11), Hg 0.68 (0.37 - 3.54), Mn 1.90 (0.35- 14.90), Ni 1.39 (0.08- 8.81), Pb 3.83 (1.20- 27.91), and Sn 1.14 (0.007-9.30). No differences in relation to sex were observed. In turn, only Cr (men) and Hg (men and women) concentrations were significantly increased with age. However, significant differences depending on the place of residence of the subjects were noted in the blood concentrations of Cd, Hg, Mn, and Pb. The current blood levels of Cd, Mn, and Pb show some remarkable differences compared to those found in previous surveys.","Biological monitoring of environmental pollution and human exposure to metals in Tarragona, Spain III Blood levelsAbs: Blood samples were obtained from 72 men and 72 women (age > 16 years) living in 3 residential areas in the vicinity of a new hazardous waste incinerator (HWI), now under construction (Tarragona, Spain). The samples were subjected to arsenic (As), beryllium (Be), cadmium (Cd),chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (TI), and vanadium (V) analyses. Beryllium, Cd, Cr, Mn, Ni, Pb, Tl, Sn, and V were measured by ICP-MS. Arsenic and Hg were determined by using hydride generation/ICP-MS. Results were analyzed in terms of age, sex, and specific place of residence. Arsenic, Be, TI, and V levels were under the respective detection limits. The geometric mean concentrations and ranges ( g/dl) of the remaining elements were the following: Cd 0.70 (0.20-3.24), Cr 0.02 (0.01 -0.11), Hg 0.68 (0.37 - 3.54), Mn 1.90 (0.35- 14.90), Ni 1.39 (0.08- 8.81), Pb 3.83 (1.20- 27.91), and Sn 1.14 (0.007-9.30). No differences in relation to sex were observed. In turn, only Cr (men) and Hg (men and women) concentrations were significantly increased with age. However, significant differences depending on the place of residence of the subjects were noted in the blood concentrations of Cd, Hg, Mn, and Pb. The current blood levels of Cd, Mn, and Pb show some remarkable differences compared to those found in previous surveys."
92,Liu et al. 2000,"Chronic combined exposure to cadmium and arsenic exacerbates nephrotoxicity, particularly in metallothionein-I/II null mice"," Cadmium (Cd) and arsenic (As) are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of Cd and As, but the toxicological interactions of these inorganic mixtures are poorly defined. Metallothionein (MT) is a cysteine-rich, metal-binding protein that plays an important role in Cd detoxication, but its role in As toxicity is less certain. To examine the role of MT in Cd- and/or As-induced nephrotoxicity, MT-I/II-knockout (MT-null) mice and background-matched wild-type (WT) mice were fed CdCl2 (100 ppm Cd) in the diet, NaAsO2 (22.5 ppm As) in the drinking water, or Cd plus As for 4 months. Subsequently, nephrotoxicity was examined by morphological and biochemical techniques. Chronic exposure to Cd produced more renal toxicity than As, and the combination of Cd and As produced even more renal injury than caused by either of the chemicals given alone. In mice receiving Cd plus As, proximal tubule degeneration and atrophy, glomerular swelling and interstitial fibrosis were more severe than those produced by either inorganic. Furthermore, lack of MT rendered MT-null mice more sensitive than WT mice to the nephrotoxicity produced by chronic Cd- and/or As-exposure. MT-null mice were especially susceptible to the toxicity produced by the combination of Cd and As, as evidenced by decreased body weight, enzymuria, glucosuria, proteinuria and nephropathy. In conclusion, this study indicates that As may potentiate Cd nephrotoxicity during the long-term, combined exposure, and that intracellular MT plays a role in decreasing the nephropathy of combined exposure to Cd and As.","Chronic combined exposure to cadmium and arsenic exacerbates nephrotoxicity, particularly in metallothionein-I/II null miceAbs: Cadmium (Cd) and arsenic (As) are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of Cd and As, but the toxicological interactions of these inorganic mixtures are poorly defined. Metallothionein (MT) is a cysteine-rich, metal-binding protein that plays an important role in Cd detoxication, but its role in As toxicity is less certain. To examine the role of MT in Cd- and/or As-induced nephrotoxicity, MT-I/II-knockout (MT-null) mice and background-matched wild-type (WT) mice were fed CdCl2 (100 ppm Cd) in the diet, NaAsO2 (22.5 ppm As) in the drinking water, or Cd plus As for 4 months. Subsequently, nephrotoxicity was examined by morphological and biochemical techniques. Chronic exposure to Cd produced more renal toxicity than As, and the combination of Cd and As produced even more renal injury than caused by either of the chemicals given alone. In mice receiving Cd plus As, proximal tubule degeneration and atrophy, glomerular swelling and interstitial fibrosis were more severe than those produced by either inorganic. Furthermore, lack of MT rendered MT-null mice more sensitive than WT mice to the nephrotoxicity produced by chronic Cd- and/or As-exposure. MT-null mice were especially susceptible to the toxicity produced by the combination of Cd and As, as evidenced by decreased body weight, enzymuria, glucosuria, proteinuria and nephropathy. In conclusion, this study indicates that As may potentiate Cd nephrotoxicity during the long-term, combined exposure, and that intracellular MT plays a role in decreasing the nephropathy of combined exposure to Cd and As."
93,Buchet and Lison 1998,Mortality by cancer in groups of the Belgian population with a moderately increased intake of arsenic," OBJECT: The dose-response relationship for lung carcinoma and other cancers at low doses of As is highly uncertain because it is based on modeling data collected in populations with a high daily intake of the element. The finding of a slightly increased exposure to arsenic in certain groups of the Belgian general population prompted us to examine whether this had repercussions on the causes of mortality. METHOD: Statistics of mortality by causes with a possible link to exposure to the element (standardized mortality ratio) were analyzed in groups of the Belgian population previously shown to have been exposed to As from natural (drinking water) and/or industrial (nonferrous metal smelter emissions) sources. RESULTS: A moderately increased absorption of As, leading to a 3- to 4- fold higher urinary excretion (35 micrograms/day as compared with 6-10 micrograms As/day in nonexposed subjects) did not enhance the mortality by diseases of the nervous system, liver and heart, and cancers. An increase in mortality by lung cancer, however, was observed in men but not women living around zinc smelters and might be related to past occupational exposure and/or smoking habits. CONCLUSION: A low to moderate level of environmental exposure to inorganic arsenic (0.3 microgram As/m3 of air; 20-50 micrograms As/l of drinking water) does not seem to affect the causes of mortality, suggesting in particular nonlinearity of the dose-response relationship for arsenic and cancer.","Mortality by cancer in groups of the Belgian population with a moderately increased intake of arsenicAbs: OBJECT: The dose-response relationship for lung carcinoma and other cancers at low doses of As is highly uncertain because it is based on modeling data collected in populations with a high daily intake of the element. The finding of a slightly increased exposure to arsenic in certain groups of the Belgian general population prompted us to examine whether this had repercussions on the causes of mortality. METHOD: Statistics of mortality by causes with a possible link to exposure to the element (standardized mortality ratio) were analyzed in groups of the Belgian population previously shown to have been exposed to As from natural (drinking water) and/or industrial (nonferrous metal smelter emissions) sources. RESULTS: A moderately increased absorption of As, leading to a 3- to 4- fold higher urinary excretion (35 micrograms/day as compared with 6-10 micrograms As/day in nonexposed subjects) did not enhance the mortality by diseases of the nervous system, liver and heart, and cancers. An increase in mortality by lung cancer, however, was observed in men but not women living around zinc smelters and might be related to past occupational exposure and/or smoking habits. CONCLUSION: A low to moderate level of environmental exposure to inorganic arsenic (0.3 microgram As/m3 of air; 20-50 micrograms As/l of drinking water) does not seem to affect the causes of mortality, suggesting in particular nonlinearity of the dose-response relationship for arsenic and cancer."
94,Lilis et al. 1985,Effects of low-level lead and arsenic exposure on copper smelter workers," An analysis of reported symptoms and their relationship with indicators of lead absorption--blood lead (Pb-B) and zinc protoporphyrin (ZPP)--and of arsenic absorption--urinary arsenic (As-U)--was undertaken among 680 active copper smelter workers. Lead and arsenic absorption in the copper smelter employees were characterized by the median values of 30.4 micrograms/dl for Pb-B, 41.5 micrograms/dl for ZPP, and 26 micrograms/L for As-U. Blood lead was 40 micrograms/dl or higher in 16.7% of cases, ZPP was 50 micrograms/dl or higher in 31.2%, and urinary arsenic was 50 micrograms/L or higher in 16.4% of currently active copper smelter workers. The number of reported symptoms (from a total of 14 symptoms) increased with ZPP levels; the relationship with Pb-B was less marked. Arsenic contributed relatively little. Mean Pb-B, ZPP, and As-U levels for subjects reporting each of the 14 symptoms were compared with those of subjects who did not report the symptoms. Mean Pb-B was found to differ significantly for one symptom, fatigue. Significant differences in mean ZPP levels were found for fatigue, sleep disturbances, weakness, paresthesia, and joint pain. Prevalence rates for these symptoms rose more markedly with increasing ZPP than with Pb-B levels. The results indicate a relationship between certain CNS and musculo-skeletal symptoms and increased lead absorption in this population. Adherence to exposure standards that preclude undue lead absorption and appropriate biological monitoring including ZPP levels, are necessary to prevent adverse, especially long-term, health effects.","Effects of low-level lead and arsenic exposure on copper smelter workersAbs: An analysis of reported symptoms and their relationship with indicators of lead absorption--blood lead (Pb-B) and zinc protoporphyrin (ZPP)--and of arsenic absorption--urinary arsenic (As-U)--was undertaken among 680 active copper smelter workers. Lead and arsenic absorption in the copper smelter employees were characterized by the median values of 30.4 micrograms/dl for Pb-B, 41.5 micrograms/dl for ZPP, and 26 micrograms/L for As-U. Blood lead was 40 micrograms/dl or higher in 16.7% of cases, ZPP was 50 micrograms/dl or higher in 31.2%, and urinary arsenic was 50 micrograms/L or higher in 16.4% of currently active copper smelter workers. The number of reported symptoms (from a total of 14 symptoms) increased with ZPP levels; the relationship with Pb-B was less marked. Arsenic contributed relatively little. Mean Pb-B, ZPP, and As-U levels for subjects reporting each of the 14 symptoms were compared with those of subjects who did not report the symptoms. Mean Pb-B was found to differ significantly for one symptom, fatigue. Significant differences in mean ZPP levels were found for fatigue, sleep disturbances, weakness, paresthesia, and joint pain. Prevalence rates for these symptoms rose more markedly with increasing ZPP than with Pb-B levels. The results indicate a relationship between certain CNS and musculo-skeletal symptoms and increased lead absorption in this population. Adherence to exposure standards that preclude undue lead absorption and appropriate biological monitoring including ZPP levels, are necessary to prevent adverse, especially long-term, health effects."
95,Fowler et al.  2004,"Oxidative stress induced by lead, cadmium and arsenic mixtures: 30-day, 90-day, and 180-day drinking water studies in rats: an overview"," Humans are frequently exposed to combinations of lead (Pb), cadmium (Cd) and Arsenic (As) but there is a paucity of actual data on the molecular effects of these agents at low dose levels. The present factorial design studies were undertaken in rats to examine the effects of these agents at LOEL dose levels on a number of molecular parameters of oxidative stress in hematopoietic and renal organ systems following oral exposure in drinking water at 30, 90 and 180 day time points. Results of these studies demonstrated dynamic, time-dependent alterations in both molecular targets and inducible oxidative stress protective systems in target cell populations. In general, cellular protective systems, which protected against oxidative damage at the 90 day time point, appeared to be finite such that molecular manifestations of oxidative stress became statistically significant at the 180 day time point for several of the combination exposure groups. These data demonstrate the importance of duration of exposure in assessing the toxic potential of Pb, Cd and As mixtures at low dose levels.","Oxidative stress induced by lead, cadmium and arsenic mixtures: 30-day, 90-day, and 180-day drinking water studies in rats: an overviewAbs: Humans are frequently exposed to combinations of lead (Pb), cadmium (Cd) and Arsenic (As) but there is a paucity of actual data on the molecular effects of these agents at low dose levels. The present factorial design studies were undertaken in rats to examine the effects of these agents at LOEL dose levels on a number of molecular parameters of oxidative stress in hematopoietic and renal organ systems following oral exposure in drinking water at 30, 90 and 180 day time points. Results of these studies demonstrated dynamic, time-dependent alterations in both molecular targets and inducible oxidative stress protective systems in target cell populations. In general, cellular protective systems, which protected against oxidative damage at the 90 day time point, appeared to be finite such that molecular manifestations of oxidative stress became statistically significant at the 180 day time point for several of the combination exposure groups. These data demonstrate the importance of duration of exposure in assessing the toxic potential of Pb, Cd and As mixtures at low dose levels."
96,Stocks 1960,"On the relations between atmospheric pollution in urban and rural localities and mortality from cancer, bronchitis and pneumonia, with particular reference to 3:4 benzopyrene, beryllium, molybdenum, vanadium and arsenic",0,"On the relations between atmospheric pollution in urban and rural localities and mortality from cancer, bronchitis and pneumonia, with particular reference to 3:4 benzopyrene, beryllium, molybdenum, vanadium and arsenicAbs:0"
97,Engel and Smith 1994,Arsenic in drinking water and mortality from vascular disease: an ecologic analysis in 30 counties in the United States," Chronic arsenic consumption can cause vascular diseases. Adverse vascular effects of arsenic in drinking water in the United States have not been studied. This study investigated the ecological relationship between the population-weighted mean arsenic concentration in public drinking water supplies and mortality from circulatory diseases in 30 U.S. counties from 1968 to 1984. Mean arsenic levels ranged from 5.4 to 91.5 micrograms/l. Standardized mortality ratios (SMRs) for diseases of arteries, arterioles, and capillaries (DAAC) (ICD 8th/9th revision, 440-448) for counties exceeding 20 micrograms/l were 1.9 (90% confidence interval [CI] = 1.7-2.1) for females and 1.6 (90% CI = 1.5-1.8) for males. The SMRs for the three subgroups of DAAC--arteriosclerosis, aortic aneurysm, and all other DAAC--tended to be elevated. With respect to the same arsenic group, the SMRs for congenital anomalies of the heart (ICD-8/9, 746/745-746) and circulatory system (ICD-8/9, 747) also tended to be elevated. Two competing interpretations emerge as possibilities: either there are spurious associations resulting from invalid outcome data or causal associations.","Arsenic in drinking water and mortality from vascular disease: an ecologic analysis in 30 counties in the United StatesAbs: Chronic arsenic consumption can cause vascular diseases. Adverse vascular effects of arsenic in drinking water in the United States have not been studied. This study investigated the ecological relationship between the population-weighted mean arsenic concentration in public drinking water supplies and mortality from circulatory diseases in 30 U.S. counties from 1968 to 1984. Mean arsenic levels ranged from 5.4 to 91.5 micrograms/l. Standardized mortality ratios (SMRs) for diseases of arteries, arterioles, and capillaries (DAAC) (ICD 8th/9th revision, 440-448) for counties exceeding 20 micrograms/l were 1.9 (90% confidence interval [CI] = 1.7-2.1) for females and 1.6 (90% CI = 1.5-1.8) for males. The SMRs for the three subgroups of DAAC--arteriosclerosis, aortic aneurysm, and all other DAAC--tended to be elevated. With respect to the same arsenic group, the SMRs for congenital anomalies of the heart (ICD-8/9, 746/745-746) and circulatory system (ICD-8/9, 747) also tended to be elevated. Two competing interpretations emerge as possibilities: either there are spurious associations resulting from invalid outcome data or causal associations."
98,Jones 1994,Survey of antimony workers: mortality 1961-1992," The mortality of a census population and a prospective cohort of men employed on an antimony smelter in the north east of England was followed up from 1961-1992. The workers studied were exposed to a variety of agents including antimony and its oxides, arsenic and arsenic oxides, sulphur dioxide, and polycyclic aromatic hydrocarbons. The regional mortality rates were used to calculate expected deaths and a group of zircon sand workers employed on the site were used as a comparison group. For the census population of men working on the smelter before 1961 a significant increase in deaths from lung cancer was found (32 observed v 14.7 expected, P &lt; 0.001). A similar excess was seen among maintenance men (12 observed v 5.3 expected P = 0.016). No such excess was found in the cohort recruited after 1960 (5 observed v 9.2 expected, maintenance workers 3 observed v 2.8 expected). There was evidence of a minimum latency period of around 20 years between first exposure and death from lung cancer. No evidence was found for a correlation between length of time worked and mortality from lung cancer. The results show that an increased risk of lung cancer existed in the workers employed before 1961, but it was not possible to attribute this excess to any particular agent. Mortality analysed by five year calendar periods of first exposure show a lessening of effect after 1955. Although the power of the study is clearly less for more recent periods of exposure the absence of any excess in the population after 1960 is encouraging.","Survey of antimony workers: mortality 1961-1992Abs: The mortality of a census population and a prospective cohort of men employed on an antimony smelter in the north east of England was followed up from 1961-1992. The workers studied were exposed to a variety of agents including antimony and its oxides, arsenic and arsenic oxides, sulphur dioxide, and polycyclic aromatic hydrocarbons. The regional mortality rates were used to calculate expected deaths and a group of zircon sand workers employed on the site were used as a comparison group. For the census population of men working on the smelter before 1961 a significant increase in deaths from lung cancer was found (32 observed v 14.7 expected, P &lt; 0.001). A similar excess was seen among maintenance men (12 observed v 5.3 expected P = 0.016). No such excess was found in the cohort recruited after 1960 (5 observed v 9.2 expected, maintenance workers 3 observed v 2.8 expected). There was evidence of a minimum latency period of around 20 years between first exposure and death from lung cancer. No evidence was found for a correlation between length of time worked and mortality from lung cancer. The results show that an increased risk of lung cancer existed in the workers employed before 1961, but it was not possible to attribute this excess to any particular agent. Mortality analysed by five year calendar periods of first exposure show a lessening of effect after 1955. Although the power of the study is clearly less for more recent periods of exposure the absence of any excess in the population after 1960 is encouraging."
99,Axelson et al. 1978,Arsenic exposure and mortality: a case-referent study from a Swedish copper smelter," An increased mortality from lung cancer, cardiovascular disease, haematolymphatic malignancy and cirrhosis of the liver has been reported among smelter workers and others exposed to arsenic. This study uses the case-referent (case-control) technique and is concerned with workers in a copper smelter in a complex work environment, characterised by the presence of trivalent arsenic in combination with sulphur dioxide and copper, and also with other agents. Lung cancer mortality was found to be increased about five-fold and cardiovascular disease about two-fold, showing a dose-response relationship to arsenic exposure. Mortality from malignant blood disease (leukaemia and myeloma) and cirrhosis of the liver was also slightly increased. This mortality pattern among the smelter workers is consistent with earlier reports. An increased mortality from cardiovascular disease in this type of industry is of particular interest as it has been reported only once before.","Arsenic exposure and mortality: a case-referent study from a Swedish copper smelterAbs: An increased mortality from lung cancer, cardiovascular disease, haematolymphatic malignancy and cirrhosis of the liver has been reported among smelter workers and others exposed to arsenic. This study uses the case-referent (case-control) technique and is concerned with workers in a copper smelter in a complex work environment, characterised by the presence of trivalent arsenic in combination with sulphur dioxide and copper, and also with other agents. Lung cancer mortality was found to be increased about five-fold and cardiovascular disease about two-fold, showing a dose-response relationship to arsenic exposure. Mortality from malignant blood disease (leukaemia and myeloma) and cirrhosis of the liver was also slightly increased. This mortality pattern among the smelter workers is consistent with earlier reports. An increased mortality from cardiovascular disease in this type of industry is of particular interest as it has been reported only once before."
100,Beckman et al. 1977,Chromosome aberrations in workers exposed to arsenic," The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Rönnskär smeltery in northern Sweden. In the smelter workers, 87 aberrations were found in 819 mitoses. The number of aberrations varied individually from 0 to 25 aberrations per 100 cells. In a control material 13 aberrations were found in 1012 mitoses. The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty.","Chromosome aberrations in workers exposed to arsenicAbs: The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Rönnskär smeltery in northern Sweden. In the smelter workers, 87 aberrations were found in 819 mitoses. The number of aberrations varied individually from 0 to 25 aberrations per 100 cells. In a control material 13 aberrations were found in 1012 mitoses. The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty."
101,Blom et al. 1985,Arsenic exposure to smelter workers: clinical and neurophysiological studies," Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/m3 before 1975 and approximately 50 micrograms/m3 thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. Only minor neurological and electromyographic abnormalities were found. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/m3 in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure.","Arsenic exposure to smelter workers: clinical and neurophysiological studiesAbs: Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/m3 before 1975 and approximately 50 micrograms/m3 thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. Only minor neurological and electromyographic abnormalities were found. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/m3 in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure."
102,Borgono et al. 1977,Arsenic in the drinking water of the city of Antofagasta: epidemiological and clinical study before and after the installation of a treatment plant," This is a second report of epidemiological and clinical investigation, related to the arsenic health problem, unique in the world, occurring in the city of Antofagasta, Chile. The arsenic problem originates in the chronic contamination of water supply in the city during 12 years. This phenomena, investigated clinically and epidemiologically and first reported in 1971, prompted the installation of a water treatment plant. This report aims to evaluate the working efficiency of the plant. The study was carried out through the examination of arsenic content in hair and nail clipping samples of the inhabitants of Antofagasta and the determination of this element in cultivated vegetables and carbonated beverages. Also a clinical study in school children, looking for cutaneous lesions attributed to arsenicism, was made. Results are encouraging. They reveal that contamination persists but in significantly lower levels.","Arsenic in the drinking water of the city of Antofagasta: epidemiological and clinical study before and after the installation of a treatment plantAbs: This is a second report of epidemiological and clinical investigation, related to the arsenic health problem, unique in the world, occurring in the city of Antofagasta, Chile. The arsenic problem originates in the chronic contamination of water supply in the city during 12 years. This phenomena, investigated clinically and epidemiologically and first reported in 1971, prompted the installation of a water treatment plant. This report aims to evaluate the working efficiency of the plant. The study was carried out through the examination of arsenic content in hair and nail clipping samples of the inhabitants of Antofagasta and the determination of this element in cultivated vegetables and carbonated beverages. Also a clinical study in school children, looking for cutaneous lesions attributed to arsenicism, was made. Results are encouraging. They reveal that contamination persists but in significantly lower levels."
103,Burgdorf et al. 1977,Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic, An elevated sister chromatid exchange (SCE) rate was found in the lymphocytes of six patients treated with arsenic. All had stigmata of arsenic use as well as biopsy-proven skin cancers. The arsenic exposed patients had a mean of 14.00 SCE/mitosis while 44 normal controls had a mean of 5.8 SCE/mitosis. Chromosome breakage analysis revealed no difference between the two groups. SCE rate has been shown to be elevated in a variety of systems where cell cultures or experimental animals were exposed to known mutagens and carcinogens. We suggest that the relationship carcinogen exposure-elevated SCE rate-cancer may also be valid in humans treated with arsenic.,Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenicAbs: An elevated sister chromatid exchange (SCE) rate was found in the lymphocytes of six patients treated with arsenic. All had stigmata of arsenic use as well as biopsy-proven skin cancers. The arsenic exposed patients had a mean of 14.00 SCE/mitosis while 44 normal controls had a mean of 5.8 SCE/mitosis. Chromosome breakage analysis revealed no difference between the two groups. SCE rate has been shown to be elevated in a variety of systems where cell cultures or experimental animals were exposed to known mutagens and carcinogens. We suggest that the relationship carcinogen exposure-elevated SCE rate-cancer may also be valid in humans treated with arsenic.
104,Cebrian et al. 1983,Chronic arsenic poisoning in the north of Mexico," 1 We compared the prevalence of signs and symptoms of chronic arsenic poisoning in two rural populations. 2 The arsenic concentration in the drinking water of the exposed population was 0.41 mg/l, and 0.007 mg/l in the control population. 3 The arsenic was present mainly (70%) in its pentavalent form. 4 The objective was to quantitate health effects and risks derived from chronic ingestion of arsenic in contaminated water. 5 In the exposed population, 21.6% of the sample, showed at least one of the cutaneous signs of chronic arsenic poisoning against 2.2% in the control town. 6 Non-specific symptoms were more prevalent in the exposed population and they occurred more frequently in those individuals with skin signs. 7 The relative risk of suffering a particular manifestation of poisoning, ranged from 1.9 to 36 times higher in the exposed population. 8 We estimated the risks above mentioned, which were derived from exposure to minute quantities of arsenic in a known proportion of its oxidation states during a life time period.","Chronic arsenic poisoning in the north of MexicoAbs: 1 We compared the prevalence of signs and symptoms of chronic arsenic poisoning in two rural populations. 2 The arsenic concentration in the drinking water of the exposed population was 0.41 mg/l, and 0.007 mg/l in the control population. 3 The arsenic was present mainly (70%) in its pentavalent form. 4 The objective was to quantitate health effects and risks derived from chronic ingestion of arsenic in contaminated water. 5 In the exposed population, 21.6% of the sample, showed at least one of the cutaneous signs of chronic arsenic poisoning against 2.2% in the control town. 6 Non-specific symptoms were more prevalent in the exposed population and they occurred more frequently in those individuals with skin signs. 7 The relative risk of suffering a particular manifestation of poisoning, ranged from 1.9 to 36 times higher in the exposed population. 8 We estimated the risks above mentioned, which were derived from exposure to minute quantities of arsenic in a known proportion of its oxidation states during a life time period."
105,Donofrio and  Wilbourn 1985,Subacute arsenic toxicity presenting on clinical and electromyographic examination as Guillain-Barre syndrome, ,Subacute arsenic toxicity presenting on clinical and electromyographic examination as Guillain-Barre syndromeAbs: 
106,Feldman et al. 1979,Peripheral neuropathy in arsenic smelter workers," We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.","Peripheral neuropathy in arsenic smelter workersAbs: We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls."
107,Heyman et al. 1956,"Peripheral neuropathy caused by arsenical intoxication: a study of 41 cases with observations on the effects of BAL (2,3, dimercapto-propanol)",NULL,"Peripheral neuropathy caused by arsenical intoxication: a study of 41 cases with observations on the effects of BAL (2,3, dimercapto-propanol)Abs:NULL"
108,Hine et al. 1977,Medical problems associated with arsenic exposure,0,Medical problems associated with arsenic exposureAbs:0
109,Lagerkvist et al. 1986,Vasospastic tendency and Raynaud's phenomenon in smelter workers exposed to arsenic," The long-term drinking of water with a high content of inorganic arsenic can lead to Raynaud's phenomenon, acrocyanosis, and gangrene of the lower legs (&quot;black foot disease&quot;). We have measured the systolic blood pressure in the finger after local cooling in 47 workers from a copper smelter who were habitually exposed to moderate amounts of arsenic dust. The controls were 48 workers not exposed to arsenic. The concentration of inorganic arsenic including its metabolites in urine was determined. We found a difference between As-exposed workers and the controls in the finger systolic pressure at skin temperatures of 10 degrees C and/or 15 degrees C expressed as a percentage of the pressure at 30 degrees C (FSP%), P less than 0.01; and the prevalence of Raynaud's phenomenon, P less than 0.05. A low FSP% was taken to indicate vasospastic tendency. There was a covariation between the duration of exposure to arsenic and the decrease in finger systolic pressure between the measurements at 30 and 10 degrees C (P less than 0.05). The uptake of arsenic at the time of the study probably did not exceed 300 micrograms/day. This was confirmed by estimation of the urinary excretion. The average total arsenic uptake was estimated to be about 4 g over 23 years, which is less than the total uptake of 20 g of arsenic by subjects who developed black foot disease. Increased vasospastic reactivity in the fingers and Raynaud's phenomenon in smelter workers seems to be due to functional alterations in the vessels caused by inhalation of arsenic.","Vasospastic tendency and Raynaud's phenomenon in smelter workers exposed to arsenicAbs: The long-term drinking of water with a high content of inorganic arsenic can lead to Raynaud's phenomenon, acrocyanosis, and gangrene of the lower legs (&quot;black foot disease&quot;). We have measured the systolic blood pressure in the finger after local cooling in 47 workers from a copper smelter who were habitually exposed to moderate amounts of arsenic dust. The controls were 48 workers not exposed to arsenic. The concentration of inorganic arsenic including its metabolites in urine was determined. We found a difference between As-exposed workers and the controls in the finger systolic pressure at skin temperatures of 10 degrees C and/or 15 degrees C expressed as a percentage of the pressure at 30 degrees C (FSP%), P less than 0.01; and the prevalence of Raynaud's phenomenon, P less than 0.05. A low FSP% was taken to indicate vasospastic tendency. There was a covariation between the duration of exposure to arsenic and the decrease in finger systolic pressure between the measurements at 30 and 10 degrees C (P less than 0.05). The uptake of arsenic at the time of the study probably did not exceed 300 micrograms/day. This was confirmed by estimation of the urinary excretion. The average total arsenic uptake was estimated to be about 4 g over 23 years, which is less than the total uptake of 20 g of arsenic by subjects who developed black foot disease. Increased vasospastic reactivity in the fingers and Raynaud's phenomenon in smelter workers seems to be due to functional alterations in the vessels caused by inhalation of arsenic."
110,Lagerkvist et al. 1988,Arsenic and Raynaud's phenomenon: vasospastic tendency and excretion of arsenic in smelter workers before and after the summer vacation," Occupational and environmental exposure to inorganic arsenic is associated with the occurrence of Raynaud's phenomenon and objectively registered abnormal finger systolic blood pressure at local cooling (FSP). A subnormal FSP during cooling indicates a vasospastic tendency. It is not known whether these phenomena are related to recent or historical long-term exposure to arsenic. Twenty-one workers from a Swedish smelter were selected on the basis of exposure to arsenic dust for more than 14 years and a previously (three years earlier) recorded subnormal FSP during local cooling. The workers were examined before and after a 4 to 8 week summer vacation. After this intermission in arsenic exposure the urinary excretion of arsenic decreased to normal values, whereas the vasospastic reaction in the fingers remained. Thus the vasospastic tendency seems to be unrelated to the most recent urinary arsenic levels. FSP levels on cooling were significantly increased as compared with the measurements made three years earlier. This suggests a gradual improvement in finger blood circulation caused by decreased exposure to arsenic as evaluated over a time period of several years. The data thus indicate that peripheral vascular disturbances caused by arsenic are dependent on long-term arsenic exposures and are independent of short-term fluctuations in arsenic exposure.","Arsenic and Raynaud's phenomenon: vasospastic tendency and excretion of arsenic in smelter workers before and after the summer vacationAbs: Occupational and environmental exposure to inorganic arsenic is associated with the occurrence of Raynaud's phenomenon and objectively registered abnormal finger systolic blood pressure at local cooling (FSP). A subnormal FSP during cooling indicates a vasospastic tendency. It is not known whether these phenomena are related to recent or historical long-term exposure to arsenic. Twenty-one workers from a Swedish smelter were selected on the basis of exposure to arsenic dust for more than 14 years and a previously (three years earlier) recorded subnormal FSP during local cooling. The workers were examined before and after a 4 to 8 week summer vacation. After this intermission in arsenic exposure the urinary excretion of arsenic decreased to normal values, whereas the vasospastic reaction in the fingers remained. Thus the vasospastic tendency seems to be unrelated to the most recent urinary arsenic levels. FSP levels on cooling were significantly increased as compared with the measurements made three years earlier. This suggests a gradual improvement in finger blood circulation caused by decreased exposure to arsenic as evaluated over a time period of several years. The data thus indicate that peripheral vascular disturbances caused by arsenic are dependent on long-term arsenic exposures and are independent of short-term fluctuations in arsenic exposure."
111,Nagymajtenyi et al. 1985,Chromosomal aberrations and fetotoxic effects of atmospheric arsenic exposure in mice," Fetal chromosomal damage and toxicity were investigated in mice exposed to the atmospheric concentrations of 28.5 mg m-3, 2.9 mg m-3 and 0.26 mg m-3 of arsenic for 4 h per day on the 9th, 10th, 11th and 12th days of gestation. On the 18th day, the fetuses were removed, and the following parameters were examined: the number of dead fetuses, retardation in growth, osteogenesis and chromosomal aberrations in liver cells. It was found that exposure to As2O3 at 28.5 mg m-3 caused fetotoxic effects and chromosomal damage, while the two lower exposures produced no significant changes with the exception of a slight decrease (9.9 and 3.1%, respectively) in fetal weight.","Chromosomal aberrations and fetotoxic effects of atmospheric arsenic exposure in miceAbs: Fetal chromosomal damage and toxicity were investigated in mice exposed to the atmospheric concentrations of 28.5 mg m-3, 2.9 mg m-3 and 0.26 mg m-3 of arsenic for 4 h per day on the 9th, 10th, 11th and 12th days of gestation. On the 18th day, the fetuses were removed, and the following parameters were examined: the number of dead fetuses, retardation in growth, osteogenesis and chromosomal aberrations in liver cells. It was found that exposure to As2O3 at 28.5 mg m-3 caused fetotoxic effects and chromosomal damage, while the two lower exposures produced no significant changes with the exception of a slight decrease (9.9 and 3.1%, respectively) in fetal weight."
112,Nordenson et al. 1978,Occupational and environmental risks in and around a smelter in northern Sweden: II. Chromosomal aberrations in workers exposed to arsenic," A significantly increased frequency of chromosomal aberrations was found among arsenic-exposed workers at the Rönnskär smelter in northern Sweden. The correlation between frequency of aberrations and arsenic exposure was rather poor. This may be due to individual variations in susceptibility to damage and to the supposed cocarcinogenic action of arsenic. The results suggested an interaction between smoking and arsenic exposure. A correlation between breaks and gaps was found, which suggests that gaps may be used as indicators of genotoxic agents.","Occupational and environmental risks in and around a smelter in northern Sweden: II. Chromosomal aberrations in workers exposed to arsenicAbs: A significantly increased frequency of chromosomal aberrations was found among arsenic-exposed workers at the Rönnskär smelter in northern Sweden. The correlation between frequency of aberrations and arsenic exposure was rather poor. This may be due to individual variations in susceptibility to damage and to the supposed cocarcinogenic action of arsenic. The results suggested an interaction between smoking and arsenic exposure. A correlation between breaks and gaps was found, which suggests that gaps may be used as indicators of genotoxic agents."
113,Smith et al. 1977,Airborne arsenic exposure and excretion of methylated arsenic compounds," First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylarsinic acid) in these samples were analyzed by selective volatilization as arsines with determination of arsenic by plasma excitation emission spectrometry. On the day preceding the urine sample collection a breathing zone measurement was made of respirable arsenic particulates for each subject. It was found that all of the subjects, including the controls excreted arsenic primarily as methylated species. Approximately 50% of the total arsenic was excreted as dimethylarsinic acid and 20% as methylarsonic acid. Slight differences in the proportion of various arsenic compounds were observed with varying levels of inorganic arsenic exposure. Amounts of arsenic species were all closely correlated with each other and with exposure. Irrespirable particulate exposures were measured on a subset of high exposure workers. Irrespirable arsenic was found to be more closely correlated with excretion of arsenic compounds than was respirable arsenic.","Airborne arsenic exposure and excretion of methylated arsenic compoundsAbs: First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylarsinic acid) in these samples were analyzed by selective volatilization as arsines with determination of arsenic by plasma excitation emission spectrometry. On the day preceding the urine sample collection a breathing zone measurement was made of respirable arsenic particulates for each subject. It was found that all of the subjects, including the controls excreted arsenic primarily as methylated species. Approximately 50% of the total arsenic was excreted as dimethylarsinic acid and 20% as methylarsonic acid. Slight differences in the proportion of various arsenic compounds were observed with varying levels of inorganic arsenic exposure. Amounts of arsenic species were all closely correlated with each other and with exposure. Irrespirable particulate exposures were measured on a subset of high exposure workers. Irrespirable arsenic was found to be more closely correlated with excretion of arsenic compounds than was respirable arsenic."
114,Tseng 1977,Effects and dose-response relationships of skin cancer and blackfoot disease with arsenic," In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this “endemic” area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose–response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease.","Effects and dose-response relationships of skin cancer and blackfoot disease with arsenicAbs: In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this “endemic” area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose–response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease."
115,Tseng et al. 1968,Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan," In a limited area on the southwest coast of Taiwan where artesian well water with a high concentration of arsenic has been used for more than 45 years, a high prevalence of chronic arsenic poisoning has been observed in recent years. The total population of this endemic area, which is defined by the presence of both patients and contaminated wells, is approximately 100,000. A general survey of 40,421 inhabitants (19,269 males and 21,152 females) of the area was made. The overall prevalence rates for skin cancer, hyperpigmentation, and keratosis were 10.6, 183.5, and 71.0/1000, respectively. The male-to-female ratio was 2.9:1 for skin cancer and 1.1:1 for hyperpigmentation and keratosis, respectively. Generally speaking, the prevalence increased steadily with age in all three conditions, though there was a decline in age groups above 69 in females with cancer or hyperpigmentation. The prevalence rate for skin cancer showed an ascending gradient according to the arsenic content of the well water, i.e., the higher the arsenic content, the more patients with skin cancer. The results were the same for hyperpigmentation and keratosis. Blackfoot disease, so-termed locally, a peripheral vascular disorder resulting in gangrene of the extremities, especially of the feet, had an overall prevalence rate of 8.9/1000. A dose-response relationship between this disease and the amount of arsenic in the well water was similar to that observed for skin cancer. The association of Blackfoot disease with hyperpigmentation, keratosis, and skin cancer was significantly higher than expected. The casual relationship between Blackfoot disease and chronic arsenicism is discussed.","Prevalence of skin cancer in an endemic area of chronic arsenicism in TaiwanAbs: In a limited area on the southwest coast of Taiwan where artesian well water with a high concentration of arsenic has been used for more than 45 years, a high prevalence of chronic arsenic poisoning has been observed in recent years. The total population of this endemic area, which is defined by the presence of both patients and contaminated wells, is approximately 100,000. A general survey of 40,421 inhabitants (19,269 males and 21,152 females) of the area was made. The overall prevalence rates for skin cancer, hyperpigmentation, and keratosis were 10.6, 183.5, and 71.0/1000, respectively. The male-to-female ratio was 2.9:1 for skin cancer and 1.1:1 for hyperpigmentation and keratosis, respectively. Generally speaking, the prevalence increased steadily with age in all three conditions, though there was a decline in age groups above 69 in females with cancer or hyperpigmentation. The prevalence rate for skin cancer showed an ascending gradient according to the arsenic content of the well water, i.e., the higher the arsenic content, the more patients with skin cancer. The results were the same for hyperpigmentation and keratosis. Blackfoot disease, so-termed locally, a peripheral vascular disorder resulting in gangrene of the extremities, especially of the feet, had an overall prevalence rate of 8.9/1000. A dose-response relationship between this disease and the amount of arsenic in the well water was similar to that observed for skin cancer. The association of Blackfoot disease with hyperpigmentation, keratosis, and skin cancer was significantly higher than expected. The casual relationship between Blackfoot disease and chronic arsenicism is discussed."
116,Webb et al. 1987,Pulmonary clearance and toxicity of respirable gallium arsenide particulates intratracheally instilled into rats," Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry.","Pulmonary clearance and toxicity of respirable gallium arsenide particulates intratracheally instilled into ratsAbs: Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry."
117,Wester et al. 1981,"Arsenic and selenium in lung, liver, and kidney tissue from dead smelter workers"," Concentrations of arsenic and selenium in lung, liver, and kidney tissue from dead smelter workers and from a control group have been determined with the aid of neutron activation analysis. A sevenfold increase of arsenic was found in lung tissue from the exposed workers compared with the control group. The median value of arsenic in lung tissue from workers dead from respiratory cancer was not higher than corresponding values from workers dead from other malignancies or from cardiovascular or other diseases. With increasing period of retirement the malignancies or from cardiovascular or other diseases. With increasing period of retirement the arsenic content diminished in liver tissue but not in lung tissue, indicating a long biological half life of arsenic in lung tissue. The workers dead from malignancies had a higher As/Se quotient than workers dead from other diseases, which does not contradict the protective theory of selenium. Accumulation of antimony, cadmium, lead and lanthanum was observed in lung tissue from the exposed workers. Six of the workers died from lung cancer and the highest concentrations of any of the elements were always observed in the lung tissue from these six cases. This observation speaks in favour of a multifactorial cause behind the excess mortality from lung cancer in smelter workers.","Arsenic and selenium in lung, liver, and kidney tissue from dead smelter workersAbs: Concentrations of arsenic and selenium in lung, liver, and kidney tissue from dead smelter workers and from a control group have been determined with the aid of neutron activation analysis. A sevenfold increase of arsenic was found in lung tissue from the exposed workers compared with the control group. The median value of arsenic in lung tissue from workers dead from respiratory cancer was not higher than corresponding values from workers dead from other malignancies or from cardiovascular or other diseases. With increasing period of retirement the malignancies or from cardiovascular or other diseases. With increasing period of retirement the arsenic content diminished in liver tissue but not in lung tissue, indicating a long biological half life of arsenic in lung tissue. The workers dead from malignancies had a higher As/Se quotient than workers dead from other diseases, which does not contradict the protective theory of selenium. Accumulation of antimony, cadmium, lead and lanthanum was observed in lung tissue from the exposed workers. Six of the workers died from lung cancer and the highest concentrations of any of the elements were always observed in the lung tissue from these six cases. This observation speaks in favour of a multifactorial cause behind the excess mortality from lung cancer in smelter workers."
118,Wingren and Axelson 1985,Mortality pattern in a glass producing area in SE Sweden," Because of discharges, mainly of lead, from glassworks in an otherwise rural and unpolluted area in southeast Sweden the population became concerned about the potential risks of cancer and an epidemiological study was requested. The total and the specific cancer mortality in the three parishes around the glassworks were found to be approximately normal, both by comparison with national death rates and the death rates of another, similarly rural, area. More interesting results, however, were obtained in several case-referent studies also undertaken to study mortality from specific cancer sites and cardiovascular disease with regard to employment in the glassworks. A significant excess of deaths from stomach cancer, especially in glassblowers, lung cancer, and cardiovascular disease was observed among the glassworkers. Occupational exposures in the glassworks, especially to arsenic, may be of aetiological importance.","Mortality pattern in a glass producing area in SE SwedenAbs: Because of discharges, mainly of lead, from glassworks in an otherwise rural and unpolluted area in southeast Sweden the population became concerned about the potential risks of cancer and an epidemiological study was requested. The total and the specific cancer mortality in the three parishes around the glassworks were found to be approximately normal, both by comparison with national death rates and the death rates of another, similarly rural, area. More interesting results, however, were obtained in several case-referent studies also undertaken to study mortality from specific cancer sites and cardiovascular disease with regard to employment in the glassworks. A significant excess of deaths from stomach cancer, especially in glassblowers, lung cancer, and cardiovascular disease was observed among the glassworkers. Occupational exposures in the glassworks, especially to arsenic, may be of aetiological importance."
119,Zaldivar 1980,"A morbid condition involving cardio-vascular, broncho-pulmonary, digestive and neural lesions in children and young adults after dietary arsenic exposure"," An investigation on the relationship between dietary arsenic exposure and cardiovascular diseases was made. In Antofagasta Commune, northern Chile, since 1955 arsenic has polluted public drinking water. This environmental contamination is of geological origin. The concentration of arsenic in drinking water for the 1955-1970 period was 0.5980 ppm (weighted mean). In the period June 1970-March 1972, the concentration decreased to 0.0815 ppm (weighted mean), due to a Water Filtration Plant which started operating in May 1970. Greater Santiago showed 0.00 ppm of arsenic in drinking water. Amongst 10 autopsied patients (age range: 1 year 7 months to 18 years) with chronic arsenical dermatosis from Antofagasta Commune, 9 showed marked fibrous intimal thickening of the arterial wall and/or restricted lumen of the left coronary artery, 2 of these 9 also exhibiting myocardial infarction. Of the 10 patients, 7 developed cardiomegaly, which was related to chronic exposure to dietary arsenic. Two series of patients with myocardial infarction under 40 years of age, one from Antofagasta Commune (exposed to arsenic), the other from Greater Santiago (not exposed to arsenic) were compared. The Yates' corrected chi 2 value (1 d.f.) being 11.7776. The difference was statistically highly significant (P approximately equal to 0.0006018). Furthermore, in Antofagasta Commune, the number of cases (&lt; 40 yr) which had myocardial infarction with chronic arsenical dermatosis were compared with the cases (&lt; 40 yr) which showed myocardial infarction without chronic arsenical dermatosis. The Yates' corrected chi 2 value (1 d.f.) was 13.0395. A highly significant difference was detected (P approximately equal to 0.0003044). Children (0-15 yr)from the two cities were also compared.(ABSTRACT TRUNCATED AT 250 WORDS)","A morbid condition involving cardio-vascular, broncho-pulmonary, digestive and neural lesions in children and young adults after dietary arsenic exposureAbs: An investigation on the relationship between dietary arsenic exposure and cardiovascular diseases was made. In Antofagasta Commune, northern Chile, since 1955 arsenic has polluted public drinking water. This environmental contamination is of geological origin. The concentration of arsenic in drinking water for the 1955-1970 period was 0.5980 ppm (weighted mean). In the period June 1970-March 1972, the concentration decreased to 0.0815 ppm (weighted mean), due to a Water Filtration Plant which started operating in May 1970. Greater Santiago showed 0.00 ppm of arsenic in drinking water. Amongst 10 autopsied patients (age range: 1 year 7 months to 18 years) with chronic arsenical dermatosis from Antofagasta Commune, 9 showed marked fibrous intimal thickening of the arterial wall and/or restricted lumen of the left coronary artery, 2 of these 9 also exhibiting myocardial infarction. Of the 10 patients, 7 developed cardiomegaly, which was related to chronic exposure to dietary arsenic. Two series of patients with myocardial infarction under 40 years of age, one from Antofagasta Commune (exposed to arsenic), the other from Greater Santiago (not exposed to arsenic) were compared. The Yates' corrected chi 2 value (1 d.f.) being 11.7776. The difference was statistically highly significant (P approximately equal to 0.0006018). Furthermore, in Antofagasta Commune, the number of cases (&lt; 40 yr) which had myocardial infarction with chronic arsenical dermatosis were compared with the cases (&lt; 40 yr) which showed myocardial infarction without chronic arsenical dermatosis. The Yates' corrected chi 2 value (1 d.f.) was 13.0395. A highly significant difference was detected (P approximately equal to 0.0003044). Children (0-15 yr)from the two cities were also compared.(ABSTRACT TRUNCATED AT 250 WORDS)"
120,Wu 1988,Occupational cancer epidemiology in the People's Republic of China," Aspects covered in this review: occupations; current methodology; important studies (vinyl chloride, cloromethyl methyl ether, bis(chloromethyl) ether, benzidine, asbestos, benzene, arsenic, chromates, coking gas, carbon, oil refineries); prospects and problems.","Occupational cancer epidemiology in the People's Republic of ChinaAbs: Aspects covered in this review: occupations; current methodology; important studies (vinyl chloride, cloromethyl methyl ether, bis(chloromethyl) ether, benzidine, asbestos, benzene, arsenic, chromates, coking gas, carbon, oil refineries); prospects and problems."
121,Ades and Kazantzis 1988,Lung cancer in a non-ferrous smelter: the role of cadmium," Lung cancer mortality was examined in a cohort of 4393 men employed at a zinc-lead-cadmium smelter. There was an excess of lung cancer (overall SMR = 124.5, 95% confidence interval 107-144) which was particularly evident for those employed for more than 20 years. A statistically significant trend in SMRs with increasing duration of employment was apparent. Quantitative estimates of exposure to cadmium and ordinal rankings for lead, arsenic, zinc, sulphur dioxide, and dust were used to calculate cumulative exposures from job histories. Matched logistic regression was used to compare the cumulative exposures of cases of lung cancer to those of controls matched for date of birth and date of starting work and surviving at the time of death of the matched cases. The increasing risk of lung cancer associated with increasing duration of employment could not be accounted for by cadmium and did not appear to be restricted to any particular process or department. Although lung cancer mortality was associated with estimates of cumulative exposure to arsenic and to lead, it was not possible to determine whether the increased risk might be due to arsenic, lead, or to other contaminants in the smelter. These results are compared with findings from other non-ferrous smelters.","Lung cancer in a non-ferrous smelter: the role of cadmiumAbs: Lung cancer mortality was examined in a cohort of 4393 men employed at a zinc-lead-cadmium smelter. There was an excess of lung cancer (overall SMR = 124.5, 95% confidence interval 107-144) which was particularly evident for those employed for more than 20 years. A statistically significant trend in SMRs with increasing duration of employment was apparent. Quantitative estimates of exposure to cadmium and ordinal rankings for lead, arsenic, zinc, sulphur dioxide, and dust were used to calculate cumulative exposures from job histories. Matched logistic regression was used to compare the cumulative exposures of cases of lung cancer to those of controls matched for date of birth and date of starting work and surviving at the time of death of the matched cases. The increasing risk of lung cancer associated with increasing duration of employment could not be accounted for by cadmium and did not appear to be restricted to any particular process or department. Although lung cancer mortality was associated with estimates of cumulative exposure to arsenic and to lead, it was not possible to determine whether the increased risk might be due to arsenic, lead, or to other contaminants in the smelter. These results are compared with findings from other non-ferrous smelters."
122,Chen et al. 1995,Increased prevalence of hypertension and long-term arsenic exposure," To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans.","Increased prevalence of hypertension and long-term arsenic exposureAbs: To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans."
123,Constan et al. 1995,A unique pattern of hepatocyte proliferation in F344 rats following long-term exposures to low levels of a chemical mixture of groundwater contaminants," Most exposures of humans to environmental agents involve mixtures of chemicals, rather than individual chemicals. Some chemicals can cause hepatocellular proliferation and act as neoplastic promoters. Little is known concerning hepatocellular proliferation caused by chemical mixtures such as those found in groundwater at hazardous waste sites. Therefore, a 6 month study was performed to investigate hepatocellular proliferation and histopathological changes in F344 rats after long-term, low-level exposure to a mixture of groundwater contaminants. The seven chemicals used are among the most frequently detected contaminants associated with hazardous waste sites; arsenic, benzene, chloroform, chromium, lead, phenol and trichloroethylene. Male F344 rats were exposed to this mixture, or submixtures of the organic or inorganic chemicals, via drinking water for 6 months. The study design included a time-course experiment (i.e. 3 and 10 days and 1, 3 and 6 months) and a dose-response experiment. Hepatocellular proliferation studies were performed by subcutaneously implanting osmotic mini-pumps to continuously deliver 5-bromo-2'-deoxyuridine for 7 days, which labeled nuclei of proliferating cells. In all groups, there were no differences in weight gain, body weight, liver weight ratios or liver-associated plasma enzymes. Light microscopic evaluation revealed no lesions related to the treatments in any animals. However, significant increases in hepatocellular labeling were observed at the 3 and 10 day and 1 month exposure time points after treatment with the full mixture, as well as the organic or inorganic submixtures. Proliferating hepatocytes expressed a unique labeling pattern surrounding large hepatic veins (0.5-2.0 mm), but not central veins. This did not appear to be a regenerative response due to cytotoxic mechanisms, as assessed by the absence of increased plasma enzyme activity and the absence of hepatocellular lesions.","A unique pattern of hepatocyte proliferation in F344 rats following long-term exposures to low levels of a chemical mixture of groundwater contaminantsAbs: Most exposures of humans to environmental agents involve mixtures of chemicals, rather than individual chemicals. Some chemicals can cause hepatocellular proliferation and act as neoplastic promoters. Little is known concerning hepatocellular proliferation caused by chemical mixtures such as those found in groundwater at hazardous waste sites. Therefore, a 6 month study was performed to investigate hepatocellular proliferation and histopathological changes in F344 rats after long-term, low-level exposure to a mixture of groundwater contaminants. The seven chemicals used are among the most frequently detected contaminants associated with hazardous waste sites; arsenic, benzene, chloroform, chromium, lead, phenol and trichloroethylene. Male F344 rats were exposed to this mixture, or submixtures of the organic or inorganic chemicals, via drinking water for 6 months. The study design included a time-course experiment (i.e. 3 and 10 days and 1, 3 and 6 months) and a dose-response experiment. Hepatocellular proliferation studies were performed by subcutaneously implanting osmotic mini-pumps to continuously deliver 5-bromo-2'-deoxyuridine for 7 days, which labeled nuclei of proliferating cells. In all groups, there were no differences in weight gain, body weight, liver weight ratios or liver-associated plasma enzymes. Light microscopic evaluation revealed no lesions related to the treatments in any animals. However, significant increases in hepatocellular labeling were observed at the 3 and 10 day and 1 month exposure time points after treatment with the full mixture, as well as the organic or inorganic submixtures. Proliferating hepatocytes expressed a unique labeling pattern surrounding large hepatic veins (0.5-2.0 mm), but not central veins. This did not appear to be a regenerative response due to cytotoxic mechanisms, as assessed by the absence of increased plasma enzyme activity and the absence of hepatocellular lesions."
124,Blakley 1987,Alterations in urethan-induced adenoma formation in mice exposed to selenium and arsenic," Female Swiss were exposed to sodium selenite (3 micrograms/ml selenium content) and sodium arsenate (80 micrograms/ml arsenic content) in the drinking water individually or in combination on alternate days for 15 weeks. Comparable water consumption was observed in all individual or combined metal-exposure groups. After 3 weeks of metal exposure, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Arsenic exposure reduced the tumor incidence (P = 0.0046) and tumor size (P less than 0.0001). Selenium exposure did not alter the tumor incidence but caused a reduction in tumor size (P = 0.022). No selenium-arsenic interactions associated with tumor size or number were observed. Urethan-induced sleeping times were unaffected by exposure to selenium (P = 0.832) or arsenic (P = 0.42), although combined metal exposure reduced the duration of urethan-induced sleep (P = 0.029) as compared to the individual metal exposures. This metal-metal interaction, which appeared to enhance the rate of urethan elimination as indicated by the reduced sleeping time, did not influence adenoma formation significantly.","Alterations in urethan-induced adenoma formation in mice exposed to selenium and arsenicAbs: Female Swiss were exposed to sodium selenite (3 micrograms/ml selenium content) and sodium arsenate (80 micrograms/ml arsenic content) in the drinking water individually or in combination on alternate days for 15 weeks. Comparable water consumption was observed in all individual or combined metal-exposure groups. After 3 weeks of metal exposure, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Arsenic exposure reduced the tumor incidence (P = 0.0046) and tumor size (P less than 0.0001). Selenium exposure did not alter the tumor incidence but caused a reduction in tumor size (P = 0.022). No selenium-arsenic interactions associated with tumor size or number were observed. Urethan-induced sleeping times were unaffected by exposure to selenium (P = 0.832) or arsenic (P = 0.42), although combined metal exposure reduced the duration of urethan-induced sleep (P = 0.029) as compared to the individual metal exposures. This metal-metal interaction, which appeared to enhance the rate of urethan elimination as indicated by the reduced sleeping time, did not influence adenoma formation significantly."
125,Valentine et al. 1992,Health response by questionnaire in arsenic-exposed populations," The health status of populations exposed to arsenic through drinking water was determined by a mailed questionnaire. Participants were selected from three communities located in Nevada with 1977 tap water arsenic levels of approximately 0.1 mg/l and one California community with 1977 levels around 0.39 mg/l. The questionnaire responses were obtained in 1979 from the four exposed communities and compared to those of a Wyoming community whose tap water levels of arsenic were less than 0.001 mg/l in 1979. No difference in health status for gastrointestinal, neurological, musculoskeletal, circulatory and skin disorders was found. The average number of years of consumption given by length of residence was 6-16 years. We conclude that the health status of these arsenic-exposed populations has not been adversely affected.","Health response by questionnaire in arsenic-exposed populationsAbs: The health status of populations exposed to arsenic through drinking water was determined by a mailed questionnaire. Participants were selected from three communities located in Nevada with 1977 tap water arsenic levels of approximately 0.1 mg/l and one California community with 1977 levels around 0.39 mg/l. The questionnaire responses were obtained in 1979 from the four exposed communities and compared to those of a Wyoming community whose tap water levels of arsenic were less than 0.001 mg/l in 1979. No difference in health status for gastrointestinal, neurological, musculoskeletal, circulatory and skin disorders was found. The average number of years of consumption given by length of residence was 6-16 years. We conclude that the health status of these arsenic-exposed populations has not been adversely affected."
126,Cuzick et al. 1992,"Ingested arsenic, keratoses, and bladder cancer","<div>&nbsp;A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945–1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).</div>","Ingested arsenic, keratoses, and bladder cancerAbs:<div>&nbsp;A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945–1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).</div>"
127,Wong et al. 1992,An ecologic study of skin cancer and environmental arsenic exposure," We conducted an epidemiologic study of skin cancer incidence rates for four counties in Montana. The two counties considered to be exposed to arsenic were Deer Lodge, containing the former Anaconda copper smelter, and Silver Bow, containing an open pit copper mine. Residents in these counties had potential exposure to arsenic and other heavy metals. Gallatin and Park counties served as controls. All histologically proven skin cancer cases during the period January 1980 through June 1986 were collected from pathology services and dermatologists in these four counties. In addition, all skin cancer cases from four dermatologists practicing in urban referral areas outside the counties were reviewed. Results were analyzed by individual as well as by two different definitions of anatomically distinct lesions: the National Cancer Institute (NCI) definition and the study definition. There were 1616 individuals with skin cancer in the four counties during the period under consideration, yielding 2252 (NCI definition) and 2451 (study definition) cases. The clinical features of the skin cancers in the exposed counties were not similar to those described for arsenic-related skin cancer. The age-adjusted annual skin cancer rates were higher for the two control counties as compared to either the county with the former smelter, Deer Lodge, or the county with the mine, Silver Bow. Our results cannot be explained by differences in ascertainment, latitude, or altitude. They can be partially explained by differences in both outdoor employment and medical practice. The overall skin cancer incidence rates for the exposed counties were well within the range of skin cancer rates observed for other locations in the United States.","An ecologic study of skin cancer and environmental arsenic exposureAbs: We conducted an epidemiologic study of skin cancer incidence rates for four counties in Montana. The two counties considered to be exposed to arsenic were Deer Lodge, containing the former Anaconda copper smelter, and Silver Bow, containing an open pit copper mine. Residents in these counties had potential exposure to arsenic and other heavy metals. Gallatin and Park counties served as controls. All histologically proven skin cancer cases during the period January 1980 through June 1986 were collected from pathology services and dermatologists in these four counties. In addition, all skin cancer cases from four dermatologists practicing in urban referral areas outside the counties were reviewed. Results were analyzed by individual as well as by two different definitions of anatomically distinct lesions: the National Cancer Institute (NCI) definition and the study definition. There were 1616 individuals with skin cancer in the four counties during the period under consideration, yielding 2252 (NCI definition) and 2451 (study definition) cases. The clinical features of the skin cancers in the exposed counties were not similar to those described for arsenic-related skin cancer. The age-adjusted annual skin cancer rates were higher for the two control counties as compared to either the county with the former smelter, Deer Lodge, or the county with the mine, Silver Bow. Our results cannot be explained by differences in ascertainment, latitude, or altitude. They can be partially explained by differences in both outdoor employment and medical practice. The overall skin cancer incidence rates for the exposed counties were well within the range of skin cancer rates observed for other locations in the United States."
128,Nygren et al. 1992,"Occupational exposure to chromium, copper and arsenic during work with impregnated wood in joinery shops"," CCA-impregnated timber contains copper, chromium and arsenic (CCA), and occupational exposure to wood dust as well as the CCA compounds may occur in work with such timber. Dust from commercially available impregnated wood has been found to contain hexavalent chromium, which is regarded as a carcinogen. Apart from determinations of the total amounts of the CCA compounds, specific determination of hexavalent chromium is therefore essential. Selective methods have been applied for control of the work environment in six joinery shops. The mean exposure to wood dust was found to be below 1 mg m-3. The mean airborne concentration of arsenic around various types of joinery machines was in the range from 0.54 to 3.1 micrograms m-3. No hexavalent chromium was detected in any samples and no increased concentrations of arsenic were found in urine from the workers. The presence of arsenic in the work-room air must be considered for appropriate assessment of the occupational environment in joinery shops.","Occupational exposure to chromium, copper and arsenic during work with impregnated wood in joinery shopsAbs: CCA-impregnated timber contains copper, chromium and arsenic (CCA), and occupational exposure to wood dust as well as the CCA compounds may occur in work with such timber. Dust from commercially available impregnated wood has been found to contain hexavalent chromium, which is regarded as a carcinogen. Apart from determinations of the total amounts of the CCA compounds, specific determination of hexavalent chromium is therefore essential. Selective methods have been applied for control of the work environment in six joinery shops. The mean exposure to wood dust was found to be below 1 mg m-3. The mean airborne concentration of arsenic around various types of joinery machines was in the range from 0.54 to 3.1 micrograms m-3. No hexavalent chromium was detected in any samples and no increased concentrations of arsenic were found in urine from the workers. The presence of arsenic in the work-room air must be considered for appropriate assessment of the occupational environment in joinery shops."
129,Blair et al.  1990,"Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: System organ studies and comparison of clinical indices of exposure"," In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats.","Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: System organ studies and comparison of clinical indices of exposureAbs: In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats."
130,Blair et al.  1990,Evidence for oxidative damage to red blood cells in mice induced by arsine gas," In animals and human beings exposed to arsine gas (AsH3) a severe and fulminant lysis of erythrocytes occurs. Little is known about the effects of subchronic exposure on the hematopoietic system or about the mechanism of hemolysis produced by arsine gas. To examine these, we exposed male and female mice to 0.000, 0.025, 0.500 and 2.500 ppm arsine gas for 6 h a day, 5 days a week during a 90-day period. After 5, 15, and 90 days of exposure, blood was collected and routine hematologic profiles were performed to document the effects of arsine gas on peripheral blood. A moderate hemolytic anemia, indicated by decreases in erythrocyte counts, hematocrits, hemoglobin concentrations and increases in mean corpuscular hemoglobins and mean corpuscular hemoglobin concentrations, was seen in blood samples collected after 5 days of exposure. In blood collected after 15 and 90 days of exposure, the anemia was less severe but a greater increase in mean corpuscular volumes and absolute reticulocyte counts revealed an active regenerative response. Higher concentrations of methemoglobin in animals in the 2.500 ppm exposure group (measured after 90 days of exposure) indicated that the rate of oxidation of heme (ferrous to ferric) increased due to exposure to arsine gas. Additionally, the presence of Heinz bodies in blood smears stained with brilliant cresyl blue and decreases in reduced glutathione concentrations in red blood cells exposed to arsine gas in vitro provide evidence that the mechanism of hemolysis involves depletion of intracellular reduced glutathione resulting in an oxidation of sulfhydryl groups in hemoglobin and possibly red cell membranes.","Evidence for oxidative damage to red blood cells in mice induced by arsine gasAbs: In animals and human beings exposed to arsine gas (AsH3) a severe and fulminant lysis of erythrocytes occurs. Little is known about the effects of subchronic exposure on the hematopoietic system or about the mechanism of hemolysis produced by arsine gas. To examine these, we exposed male and female mice to 0.000, 0.025, 0.500 and 2.500 ppm arsine gas for 6 h a day, 5 days a week during a 90-day period. After 5, 15, and 90 days of exposure, blood was collected and routine hematologic profiles were performed to document the effects of arsine gas on peripheral blood. A moderate hemolytic anemia, indicated by decreases in erythrocyte counts, hematocrits, hemoglobin concentrations and increases in mean corpuscular hemoglobins and mean corpuscular hemoglobin concentrations, was seen in blood samples collected after 5 days of exposure. In blood collected after 15 and 90 days of exposure, the anemia was less severe but a greater increase in mean corpuscular volumes and absolute reticulocyte counts revealed an active regenerative response. Higher concentrations of methemoglobin in animals in the 2.500 ppm exposure group (measured after 90 days of exposure) indicated that the rate of oxidation of heme (ferrous to ferric) increased due to exposure to arsine gas. Additionally, the presence of Heinz bodies in blood smears stained with brilliant cresyl blue and decreases in reduced glutathione concentrations in red blood cells exposed to arsine gas in vitro provide evidence that the mechanism of hemolysis involves depletion of intracellular reduced glutathione resulting in an oxidation of sulfhydryl groups in hemoglobin and possibly red cell membranes."
131,Gerhardsson et al. 1988,Fatal arsenic poisoning - a case report," A worker was buried under arsenic trioxide in an industrial accident. He was almost immediately released but had inhaled and swallowed substantial amounts of arsenic dust. In spite of intensive treatment, circulatory collapse could not be prevented, and he died 6 h after the exposure. The treatment, autopsy findings, and arsenic concentrations in tissues and body fluids are described and discussed.","Fatal arsenic poisoning - a case reportAbs: A worker was buried under arsenic trioxide in an industrial accident. He was almost immediately released but had inhaled and swallowed substantial amounts of arsenic dust. In spite of intensive treatment, circulatory collapse could not be prevented, and he died 6 h after the exposure. The treatment, autopsy findings, and arsenic concentrations in tissues and body fluids are described and discussed."
132,Hall and Harruff 1989,Fatal cardiac arrhythmia in a patient with interstitial myocarditis related to chronic arsenic poisoning," We have reported the case of a 42-year-old man exposed to arsenic at least three times over a ten-month period from an agricultural source. He showed classical symptoms and signs of arsenic poisoning. During chelation therapy and apparent recovery from the poisoning, he suddenly and unexpectedly died; postmortem examination revealed a myocarditis similar to that reported previously. The case demonstrates the need for electrocardiographic monitoring of all patients with arsenic poisoning, during both the initial phase of the illness and convalescence.","Fatal cardiac arrhythmia in a patient with interstitial myocarditis related to chronic arsenic poisoningAbs: We have reported the case of a 42-year-old man exposed to arsenic at least three times over a ten-month period from an agricultural source. He showed classical symptoms and signs of arsenic poisoning. During chelation therapy and apparent recovery from the poisoning, he suddenly and unexpectedly died; postmortem examination revealed a myocarditis similar to that reported previously. The case demonstrates the need for electrocardiographic monitoring of all patients with arsenic poisoning, during both the initial phase of the illness and convalescence."
133,Hong et al. 1989,Hematopoietic effects in mice exposed to arsine gas," Arsine gas is a potent hemolytic agent. Concern about semiconductor workers prompted an in-depth study of arsine at the National Institute of Environmental Health Sciences to determine the hematopoietic effects of prolonged exposure to this gas. Female B6C3F1 mice were exposed by inhalation to 0, 0.5, 2.5, and 5 ppm arsine, 6 hr/day for 14 days. Body weights of exposed mice were comparable to those of controls, but a marked, concentration-related splenomegaly was observed. Higher level arsine exposure produced statistically significant decreases in red blood cells, hematocrit and hemoglobin, with increases in white blood cell counts and mean corpuscular volume of red blood cells. Erythropoiesis as measured by quantitation of erythroid precursors in culture revealed a marrow reduction of colony-forming unit erythroids/femur cells for all treated groups on Day 3 postexposure and only at the 5 ppm dose group on 24 days postexposure, while splenic erythropoiesis increased at higher concentrations of arsine. There was no alteration in bone marrow cellularity and a less significant effect on granulocyte-macrophage progenitors. A 12-week study of arsine at 0, 0.025, 0.5, and 2.5 ppm (6 hr/day) by inhalation showed similar effects on hematopoiesis in mice. In conclusion, arsine exposure at low concentrations produces a stress on the hematopoietic system characterized by hemolysis, which persists for a prolonged period following exposure.","Hematopoietic effects in mice exposed to arsine gasAbs: Arsine gas is a potent hemolytic agent. Concern about semiconductor workers prompted an in-depth study of arsine at the National Institute of Environmental Health Sciences to determine the hematopoietic effects of prolonged exposure to this gas. Female B6C3F1 mice were exposed by inhalation to 0, 0.5, 2.5, and 5 ppm arsine, 6 hr/day for 14 days. Body weights of exposed mice were comparable to those of controls, but a marked, concentration-related splenomegaly was observed. Higher level arsine exposure produced statistically significant decreases in red blood cells, hematocrit and hemoglobin, with increases in white blood cell counts and mean corpuscular volume of red blood cells. Erythropoiesis as measured by quantitation of erythroid precursors in culture revealed a marrow reduction of colony-forming unit erythroids/femur cells for all treated groups on Day 3 postexposure and only at the 5 ppm dose group on 24 days postexposure, while splenic erythropoiesis increased at higher concentrations of arsine. There was no alteration in bone marrow cellularity and a less significant effect on granulocyte-macrophage progenitors. A 12-week study of arsine at 0, 0.025, 0.5, and 2.5 ppm (6 hr/day) by inhalation showed similar effects on hematopoiesis in mice. In conclusion, arsine exposure at low concentrations produces a stress on the hematopoietic system characterized by hemolysis, which persists for a prolonged period following exposure."
134,Lu and Chen 1991,Prevalence of hepatitis B surface antigen carrier status among residents in the endemic area of chronic arsenicism in Taiwan," Residents in the endemic area of blackfoot disease (BFD), a unique peripheral artery disease associated with long-term arsenic exposure, have been reported to have a significantly high mortality from hepatocellular carcinoma (HCC). A total of 129 BFD patients and 374 age-sex-residence-matched community controls were studied to examine their hepatitis B surface antigen (HBsAg) carrier status by radioimmunoassays. Residents in the endemic area had a HBsAg carrier rate (20.2%) similar to that of the general population in Taiwan. The rate was the same among BFD patients (20.9%) and matched controls (20.1%). There was no significant difference in HBsAg carrier rate among subjects who have consumed high-arsenic artesion well water for different periods of time. The rate was also similar in villages with differences in blackfoot disease prevalence, in type of wells for drinking water, as well as in arsenic content in well water. Arsenic seems to increase HCC risk of residents in this endemic area where the HBsAg carrier status is homogeneously prevalent with a rate similar to that of the general population in Taiwan.","Prevalence of hepatitis B surface antigen carrier status among residents in the endemic area of chronic arsenicism in TaiwanAbs: Residents in the endemic area of blackfoot disease (BFD), a unique peripheral artery disease associated with long-term arsenic exposure, have been reported to have a significantly high mortality from hepatocellular carcinoma (HCC). A total of 129 BFD patients and 374 age-sex-residence-matched community controls were studied to examine their hepatitis B surface antigen (HBsAg) carrier status by radioimmunoassays. Residents in the endemic area had a HBsAg carrier rate (20.2%) similar to that of the general population in Taiwan. The rate was the same among BFD patients (20.9%) and matched controls (20.1%). There was no significant difference in HBsAg carrier rate among subjects who have consumed high-arsenic artesion well water for different periods of time. The rate was also similar in villages with differences in blackfoot disease prevalence, in type of wells for drinking water, as well as in arsenic content in well water. Arsenic seems to increase HCC risk of residents in this endemic area where the HBsAg carrier status is homogeneously prevalent with a rate similar to that of the general population in Taiwan."
135,Morton and Caron 1989,Encephalopathy: an uncommon manifestation of workplace arsenic poisoning?," This report describes two cases of chronic encephalopathy associated with occupational exposure to arsenic fumes from hot pressurized impregnation of wood. Both cases displayed symptoms of cognitive impairment with onset 14-18 months after start of occupational exposure to arsenic fumes. Laboratory confirmation was provided by elevated urine arsenic levels. One patient was hospitalized for apparent psychiatric reasons. Neuropsychologic testing of one case showed typical and relatively mild impairments of new learning, recent memory, and concentration in addition to the psychological symptoms. Symptoms in both cases disappeared following cessation of exposure and return of urine arsenic excretion to normal levels. In future studies of workers exposed to arsenic, documentation of mild impairment of cognitive function should be sought using neurobehavioral test batteries.","Encephalopathy: an uncommon manifestation of workplace arsenic poisoning?Abs: This report describes two cases of chronic encephalopathy associated with occupational exposure to arsenic fumes from hot pressurized impregnation of wood. Both cases displayed symptoms of cognitive impairment with onset 14-18 months after start of occupational exposure to arsenic fumes. Laboratory confirmation was provided by elevated urine arsenic levels. One patient was hospitalized for apparent psychiatric reasons. Neuropsychologic testing of one case showed typical and relatively mild impairments of new learning, recent memory, and concentration in addition to the psychological symptoms. Symptoms in both cases disappeared following cessation of exposure and return of urine arsenic excretion to normal levels. In future studies of workers exposed to arsenic, documentation of mild impairment of cognitive function should be sought using neurobehavioral test batteries."
136,Oh 1991,Electrophysiological profile in arsenic neuropathy, Comprehensive electrophysiological studies were performed on 13 patients with arsenic neuropathy. The most prominent finding was a marked abnormality in sensory nerve conduction in the presence of moderate abnormalities in motor nerve conduction. The motor nerve conduction studies and needle EMG were typical of those seen in axonal degeneration which was confirmed by sural nerve biopsy.,Electrophysiological profile in arsenic neuropathyAbs: Comprehensive electrophysiological studies were performed on 13 patients with arsenic neuropathy. The most prominent finding was a marked abnormality in sensory nerve conduction in the presence of moderate abnormalities in motor nerve conduction. The motor nerve conduction studies and needle EMG were typical of those seen in axonal degeneration which was confirmed by sural nerve biopsy.
137,Leffler et al. 1984,Lung retention of antimony and arsenic in hamsters after the intratracheal instillation of industrial dust," Airborne factory dust (with a volume median diameter of 5.0 micron and a geometric standard deviation of 2.1 micron) from a Swedish copper smeltery contained antimony (Sb) (1.6 weight %) and arsenic (As) (19 weight %). The dust was neutron activated and intratracheally instilled in hamsters. In vivo measurements of lung clearance were undertaken of the radionuclides 76As, 122Sb, and 124Sb. Comparison was made with pure substances of antimony trioxide (Sb2O3) and arsenic trioxide (As2O3). Two phases were recognized in the clearance curves. The approximate half-time for the initial phase was 13 h for As2O3, 20 h for arsenic dust, about 40 h for Sb2O3, and about 30 h for antimony dust. The second phase had an approximate half-time of 20-40 d for Sb2O3 and antimony dust. Because of the short physical half-life of 76As, the second phase of the lung clearance was not possible to follow for AS2O3 and arsenic dust. The observed differences in clearance were primarily related to the solubility of the dust particles in saline, while particle size seemed to be less important in this instillation experiment. The low solubility of antimony in factory dust combined with a long biological half-time may be of importance in explaining the observed lung accumulation of antimony in exposed workers. The greater solubility and shorter biological half-time restricted the lung retention of arsenic.","Lung retention of antimony and arsenic in hamsters after the intratracheal instillation of industrial dustAbs: Airborne factory dust (with a volume median diameter of 5.0 micron and a geometric standard deviation of 2.1 micron) from a Swedish copper smeltery contained antimony (Sb) (1.6 weight %) and arsenic (As) (19 weight %). The dust was neutron activated and intratracheally instilled in hamsters. In vivo measurements of lung clearance were undertaken of the radionuclides 76As, 122Sb, and 124Sb. Comparison was made with pure substances of antimony trioxide (Sb2O3) and arsenic trioxide (As2O3). Two phases were recognized in the clearance curves. The approximate half-time for the initial phase was 13 h for As2O3, 20 h for arsenic dust, about 40 h for Sb2O3, and about 30 h for antimony dust. The second phase had an approximate half-time of 20-40 d for Sb2O3 and antimony dust. Because of the short physical half-life of 76As, the second phase of the lung clearance was not possible to follow for AS2O3 and arsenic dust. The observed differences in clearance were primarily related to the solubility of the dust particles in saline, while particle size seemed to be less important in this instillation experiment. The low solubility of antimony in factory dust combined with a long biological half-time may be of importance in explaining the observed lung accumulation of antimony in exposed workers. The greater solubility and shorter biological half-time restricted the lung retention of arsenic."
138,Blackwell and Robbins 1979,Arsine (arsenic hydride) poisoning in the workplace," The National Institute for Occupational Safety and Health (NIOSH) recommends that appropriate workpractices be implemented to reduce the risk of worker exposure to arsine (AsH3) gas. There is a high potential for the generation of arsine gas when inorganic arsenic is exposed to nascent (freshly formed) hydrogen. This recommendation is based on several reports of worker exposure to arsine resulting in severe toxic effects or death. Most of the reported cases occurred when arsine was accidently generated during an industrial process. NIOSH would like to inform the occupational health community of some of the circumstances in which workers have been poisoned by arsine, with particular emphasis on the underlying mechanisms of generating the gas. We request that producers and distributors of arsenic and materials containing arsenic transmit information to their customers and employees, and that professional associations and unions inform their members. Stibine (SbH3), another toxic gas, if formed when antimony is exposed to nascent hydrogen. In most situations where arsine can be formed if antimony is present. Therefore, similar work practices should be implemented to reduce the risk of worker exposure to stibine.","Arsine (arsenic hydride) poisoning in the workplaceAbs: The National Institute for Occupational Safety and Health (NIOSH) recommends that appropriate workpractices be implemented to reduce the risk of worker exposure to arsine (AsH3) gas. There is a high potential for the generation of arsine gas when inorganic arsenic is exposed to nascent (freshly formed) hydrogen. This recommendation is based on several reports of worker exposure to arsine resulting in severe toxic effects or death. Most of the reported cases occurred when arsine was accidently generated during an industrial process. NIOSH would like to inform the occupational health community of some of the circumstances in which workers have been poisoned by arsine, with particular emphasis on the underlying mechanisms of generating the gas. We request that producers and distributors of arsenic and materials containing arsenic transmit information to their customers and employees, and that professional associations and unions inform their members. Stibine (SbH3), another toxic gas, if formed when antimony is exposed to nascent hydrogen. In most situations where arsine can be formed if antimony is present. Therefore, similar work practices should be implemented to reduce the risk of worker exposure to stibine."
139,Lai et al. 1994,Ingested inorganic arsenic and prevalence of diabetes mellitus," To examine the association between ingested inorganic arsenic and prevalence of diabetes mellitus, in 1988, the authors studied 891 adults residing in villages in southern Taiwan where arseniasis is hyperendemic. The status of diabetes mellitus was determined by an oral glucose tolerance test and a history of diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic exposure in parts per million-years was calculated from the detailed history of residential addresses and duration of drinking artesian well water obtained through standardized interviews based on a structured questionnaire and the arsenic concentration in well water. The body mass index was derived from body height and weight measured according to a standard protocol, while the physical activity at work was also obtained by questionnaire interviews. Residents in villages where the chronic arseniasis was hyperendemic had a twofold increase in age-and sex-adjusted prevalence of diabetes mellitus compared with residents in Taipei City and the Taiwan area. There was a dose-response relation between cumulative arsenic exposure and prevalence of diabetes mellitus. The relation remained significant after adjustment for age, sex, body mass index, and activity level at work by a multiple logistic regression analysis giving a multivariate-adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a cumulative arsenic exposure of 0.1–15.0 and greater than 15.0 ppm-year compared with those who were unexposed. These results suggest the chronic arsenic exposure may induce diabetes mellitus in humans.","Ingested inorganic arsenic and prevalence of diabetes mellitusAbs: To examine the association between ingested inorganic arsenic and prevalence of diabetes mellitus, in 1988, the authors studied 891 adults residing in villages in southern Taiwan where arseniasis is hyperendemic. The status of diabetes mellitus was determined by an oral glucose tolerance test and a history of diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic exposure in parts per million-years was calculated from the detailed history of residential addresses and duration of drinking artesian well water obtained through standardized interviews based on a structured questionnaire and the arsenic concentration in well water. The body mass index was derived from body height and weight measured according to a standard protocol, while the physical activity at work was also obtained by questionnaire interviews. Residents in villages where the chronic arseniasis was hyperendemic had a twofold increase in age-and sex-adjusted prevalence of diabetes mellitus compared with residents in Taipei City and the Taiwan area. There was a dose-response relation between cumulative arsenic exposure and prevalence of diabetes mellitus. The relation remained significant after adjustment for age, sex, body mass index, and activity level at work by a multiple logistic regression analysis giving a multivariate-adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a cumulative arsenic exposure of 0.1–15.0 and greater than 15.0 ppm-year compared with those who were unexposed. These results suggest the chronic arsenic exposure may induce diabetes mellitus in humans."
140,Carlson-Lynch et al. 1994,Arsenic risk assessment," We review recent publications by Hopenhayn-Rich et al. and Smith et al. regarding two critical issues in arsenic risk assessment: the role of methylation in the dose-response relationship and the role of internal cancers. Hopenhayn-Rich et al. applied simple linear regression to data from several studies to determine whether the percentage of inorganic arsenic in urine increases with increasing dose. Although their results failed to show a correlation between percent inorganic arsenic and urinary arsenic concentration, their evaluation does not demonstrate the absence of a methylation threshold because of the relatively low level of arsenic in urine and the use of grab samples in evaluating methylating capacity. Using data from an epidemiological study in Taiwan, Smith et al. have indicated that arsenic could be an important risk factor not only for skin cancer (the basis of the current EPA cancer slope factor), but also for several internal cancers including lung, liver, bladder, and kidney. We note the following deficiencies in the analysis of Smith et al: 1) the likely underestimated exposure estimate due to lack of consideration on nonwater sources of arsenic and the underestimate of water consumption, 2) lack of consideration of detoxification in estimating potential risks from low-level exposures typical of the U.S. population, and 3) lack of consideration of key differences, particularly nutritional differences, between the Taiwanese and U.S. populations that could affect potential risks.","Arsenic risk assessmentAbs: We review recent publications by Hopenhayn-Rich et al. and Smith et al. regarding two critical issues in arsenic risk assessment: the role of methylation in the dose-response relationship and the role of internal cancers. Hopenhayn-Rich et al. applied simple linear regression to data from several studies to determine whether the percentage of inorganic arsenic in urine increases with increasing dose. Although their results failed to show a correlation between percent inorganic arsenic and urinary arsenic concentration, their evaluation does not demonstrate the absence of a methylation threshold because of the relatively low level of arsenic in urine and the use of grab samples in evaluating methylating capacity. Using data from an epidemiological study in Taiwan, Smith et al. have indicated that arsenic could be an important risk factor not only for skin cancer (the basis of the current EPA cancer slope factor), but also for several internal cancers including lung, liver, bladder, and kidney. We note the following deficiencies in the analysis of Smith et al: 1) the likely underestimated exposure estimate due to lack of consideration on nonwater sources of arsenic and the underestimate of water consumption, 2) lack of consideration of detoxification in estimating potential risks from low-level exposures typical of the U.S. population, and 3) lack of consideration of key differences, particularly nutritional differences, between the Taiwanese and U.S. populations that could affect potential risks."
141,Buchet et al. 1994,Assessment of exposure to inorganic arsenic following ingestion of marine organisms by volunteers," A study was undertaken to assess whether the consumption of fish and shellfish containing a high concentration (&gt; 1500 micrograms/kg) of organoarsenical compounds was associated with the release of a significant amount of inorganic arsenic (Asi) in vivo. Volunteers were given a known quantity of seafood (ray, cod, plaice, mussel) whose content in total arsenic (As), Asi, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was determined. In addition to the total amount of As excreted within 48 hours, that of Asi and its methylated metabolites (MMA, DMA) was also monitored and compared with that expected on the basis of the results of our previous studies on the toxicokinetics of Asi, MMA, and DMA in humans. Ingestion of ray, cod, or plaice does not seem to be associated with a significant release of Asi in vivo. Following consumption of mussels, however, the amount of DMA excreted in urine is significantly higher than that expected on the basis of the amount of Asi and its methylated derivatives already present in the shellfish. It was also noted that among the different marine organisms analyzed (ray, cod, plaice, sole, sea-bream, mussel), the highest proportion of Asi (on the average 3% of the total) was found in mussels. Further metabolic studies are justified to assess the risk of exposure to Asi associated with the consumption of shellfish. In view of the possible release of dimethylarsenic acid from some organoarsenicals, biological monitoring of occupational exposure to Asi by the measurement of its methylated metabolites can provide misleading results if the workers have consumed some marine organisms within 48 hr before urine collection.","Assessment of exposure to inorganic arsenic following ingestion of marine organisms by volunteersAbs: A study was undertaken to assess whether the consumption of fish and shellfish containing a high concentration (&gt; 1500 micrograms/kg) of organoarsenical compounds was associated with the release of a significant amount of inorganic arsenic (Asi) in vivo. Volunteers were given a known quantity of seafood (ray, cod, plaice, mussel) whose content in total arsenic (As), Asi, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was determined. In addition to the total amount of As excreted within 48 hours, that of Asi and its methylated metabolites (MMA, DMA) was also monitored and compared with that expected on the basis of the results of our previous studies on the toxicokinetics of Asi, MMA, and DMA in humans. Ingestion of ray, cod, or plaice does not seem to be associated with a significant release of Asi in vivo. Following consumption of mussels, however, the amount of DMA excreted in urine is significantly higher than that expected on the basis of the amount of Asi and its methylated derivatives already present in the shellfish. It was also noted that among the different marine organisms analyzed (ray, cod, plaice, sole, sea-bream, mussel), the highest proportion of Asi (on the average 3% of the total) was found in mussels. Further metabolic studies are justified to assess the risk of exposure to Asi associated with the consumption of shellfish. In view of the possible release of dimethylarsenic acid from some organoarsenicals, biological monitoring of occupational exposure to Asi by the measurement of its methylated metabolites can provide misleading results if the workers have consumed some marine organisms within 48 hr before urine collection."
142,Das et al. 1995,"Arsenic in ground water in six districts of West Bengal, India: The biggest arsenic calamity in the world: Part 2: Arsenic concentration in drinking water, hair, nails, urine, skin-scale and liver tissue (biopsy) of the affected people"," In six districts of West Bengal arsenic has been found in ground water above the maximum permissible limit recommended by the WHO of 0.05 mg l-1. This water is used by the villagers for drinking, cooking and other household purposes. These six districts have an area of 34,000 km2 and hold a population of 30 million. Over the last five years we have surveyed only a few small areas of these six affected districts and our survey revealed that, at present, at least 800,000 people from 312 villages in 37 blocks are drinking contaminated water and more than 175,000 people are showing arsenical skin lesions that are the late stages of manifestation of arsenic toxicity. Most of the three stages of arsenic-related clinical manifestations are observed amongst the affected people. The common symptoms are conjunctivitis, melanosis, depigmentation, keratosis and hyperkeratosis; cases of gangrene and malignant neoplasms are also observed. The source of arsenic is geological. We have analysed thousands of arsenic contaminated water samples. Most of the water samples contain a mixture of arsenite and arsenate and in none of them could we detect methylarsonic or dimethylarsenic acid. We have also analysed a large number of urine, hair and nail samples, several skin-scales and some liver tissues (biopsy samples) of the people drinking the arsenic contaminated water and showing arsenical skin lesions. Flow injection hydride generation atomic absorption spectrometry (FI-HGAAS) was used for the analysis of hair, nails, urine and skin-scale after decomposition by various techniques. The liver tissues were analysed by Zeeman corrected-ETAAS using a few milligrams of the biopsy samples.","Arsenic in ground water in six districts of West Bengal, India: The biggest arsenic calamity in the world: Part 2: Arsenic concentration in drinking water, hair, nails, urine, skin-scale and liver tissue (biopsy) of the affected peopleAbs: In six districts of West Bengal arsenic has been found in ground water above the maximum permissible limit recommended by the WHO of 0.05 mg l-1. This water is used by the villagers for drinking, cooking and other household purposes. These six districts have an area of 34,000 km2 and hold a population of 30 million. Over the last five years we have surveyed only a few small areas of these six affected districts and our survey revealed that, at present, at least 800,000 people from 312 villages in 37 blocks are drinking contaminated water and more than 175,000 people are showing arsenical skin lesions that are the late stages of manifestation of arsenic toxicity. Most of the three stages of arsenic-related clinical manifestations are observed amongst the affected people. The common symptoms are conjunctivitis, melanosis, depigmentation, keratosis and hyperkeratosis; cases of gangrene and malignant neoplasms are also observed. The source of arsenic is geological. We have analysed thousands of arsenic contaminated water samples. Most of the water samples contain a mixture of arsenite and arsenate and in none of them could we detect methylarsonic or dimethylarsenic acid. We have also analysed a large number of urine, hair and nail samples, several skin-scales and some liver tissues (biopsy samples) of the people drinking the arsenic contaminated water and showing arsenical skin lesions. Flow injection hydride generation atomic absorption spectrometry (FI-HGAAS) was used for the analysis of hair, nails, urine and skin-scale after decomposition by various techniques. The liver tissues were analysed by Zeeman corrected-ETAAS using a few milligrams of the biopsy samples."
143,Mushak 1985,Potential impact of acid precipitation on arsenic and selenium," The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling.","Potential impact of acid precipitation on arsenic and seleniumAbs: The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling."
144,Peplow and Edmonds 2004,"Health risks associated with contamination of groundwater by abandoned mines near Twisp in Okanogan County, Washington, USA"," #Abandoned mines are known to contaminate private drinking water wells with toxic metals and arsenic (As). Little attention is given, however, to sites in rural areas with low population densities where natural, geogenic sources of contaminants might also occur. This study measured arsenic and trace element exposure among residents consuming water from wells adjacent to abandoned mines near Twisp, in Okanogan County, Washington, USA, estimated the risk of adverse health effects, and considered the degree of uncertainty associated with the assessed risk. Water samples were collected between October 1999 and June 2001. Average As concentrations ranged from <1 to 298 microg L(-1), lead (Pb) ranged from 0 to 94 microg L(-1), cadmium (Cd) 0-5 microg L(-1), and selenium (Se) 0-390 microg L(-1). Concentrations varied seasonally with maximum concentrations occurring in conjunction with snow-melt. The calculated risk of mortality from cancer following exposure to As at average concentrations as low as 8 microg L(-1) was greater than one in 10,000. Additional noncarcinogenic risks are associated with exposure to As, Cd, Pb and Se. A potentially affected population, estimated to be between 1000 and 1287 residents, live within a 6.5-km (4-mile) radius of the study site. This study emphasises the need to test drinking water wells in the vicinity of abandoned mines during times of maximum snow-melt to determine the extent of risk to human health. Residents drinking water from wells tested in this study who want to reduce the estimated carcinogenic risk and the noncarcinogenic hazard quotient should consider treating their water or find alternative sources.","Health risks associated with contamination of groundwater by abandoned mines near Twisp in Okanogan County, Washington, USAAbs: #Abandoned mines are known to contaminate private drinking water wells with toxic metals and arsenic (As). Little attention is given, however, to sites in rural areas with low population densities where natural, geogenic sources of contaminants might also occur. This study measured arsenic and trace element exposure among residents consuming water from wells adjacent to abandoned mines near Twisp, in Okanogan County, Washington, USA, estimated the risk of adverse health effects, and considered the degree of uncertainty associated with the assessed risk. Water samples were collected between October 1999 and June 2001. Average As concentrations ranged from <1 to 298 microg L(-1), lead (Pb) ranged from 0 to 94 microg L(-1), cadmium (Cd) 0-5 microg L(-1), and selenium (Se) 0-390 microg L(-1). Concentrations varied seasonally with maximum concentrations occurring in conjunction with snow-melt. The calculated risk of mortality from cancer following exposure to As at average concentrations as low as 8 microg L(-1) was greater than one in 10,000. Additional noncarcinogenic risks are associated with exposure to As, Cd, Pb and Se. A potentially affected population, estimated to be between 1000 and 1287 residents, live within a 6.5-km (4-mile) radius of the study site. This study emphasises the need to test drinking water wells in the vicinity of abandoned mines during times of maximum snow-melt to determine the extent of risk to human health. Residents drinking water from wells tested in this study who want to reduce the estimated carcinogenic risk and the noncarcinogenic hazard quotient should consider treating their water or find alternative sources."
145,Kilburn and Warshaw 1995,Neurotoxic effects from residential exposure to chemicals from an oil reprocessing facility and superfund site," Neurotoxicity has been described in workers exposed to solvents, PCBs, certain metals, and polyaromatic hydrocarbons but not often in residents near refineries or factories. We compared the neurobehavioral performance of residents near a plant that reprocessed used motor oil and chemical waste from 1966?1983 to referents from beyond the plant's modeled air dispersal and water drainage zones. Neurophysiological and psychological tests, a Profile of Mood States (POMS) and a symptom questionnaire were administered to 131 subjects exposed at the site who were matched for age, sex, and ethnicity 2:1 with 66 unexposed subjects from 35 km away. Test scores were adjusted for a 1.4-year difference in educational attainment by coefficients from regression equations but not for income as the latter coefficients were not significant. Exposed subjects were significantly impaired for body balance (sway speed) and simple and two choice visual reaction time as compared to referents. Blink reflex latency (R-1) and eye closure speed were normal in both groups. Cognitive function in the exposed was impaired as measured by Culture Fair and by block design from the WAIS. Placing pegs in a grooved board and making of trails (A and B) were also impaired. Group differences in recall and memory were not significant. The exposed group's symptom frequencies and POMS scores for depression, anger, confusion, tension, and fatigue were elevated indicating depression. Confounding from medical and neurological disorders or occupational exposures was minimal. Subjects exposed residentially for up to 17 years to chemicals dispersed from a waste oil reprocessing plant showed neurophysiological and neuropsychological impairment.","Neurotoxic effects from residential exposure to chemicals from an oil reprocessing facility and superfund siteAbs: Neurotoxicity has been described in workers exposed to solvents, PCBs, certain metals, and polyaromatic hydrocarbons but not often in residents near refineries or factories. We compared the neurobehavioral performance of residents near a plant that reprocessed used motor oil and chemical waste from 1966?1983 to referents from beyond the plant's modeled air dispersal and water drainage zones. Neurophysiological and psychological tests, a Profile of Mood States (POMS) and a symptom questionnaire were administered to 131 subjects exposed at the site who were matched for age, sex, and ethnicity 2:1 with 66 unexposed subjects from 35 km away. Test scores were adjusted for a 1.4-year difference in educational attainment by coefficients from regression equations but not for income as the latter coefficients were not significant. Exposed subjects were significantly impaired for body balance (sway speed) and simple and two choice visual reaction time as compared to referents. Blink reflex latency (R-1) and eye closure speed were normal in both groups. Cognitive function in the exposed was impaired as measured by Culture Fair and by block design from the WAIS. Placing pegs in a grooved board and making of trails (A and B) were also impaired. Group differences in recall and memory were not significant. The exposed group's symptom frequencies and POMS scores for depression, anger, confusion, tension, and fatigue were elevated indicating depression. Confounding from medical and neurological disorders or occupational exposures was minimal. Subjects exposed residentially for up to 17 years to chemicals dispersed from a waste oil reprocessing plant showed neurophysiological and neuropsychological impairment."
146,Lisiewicz 1993,Immunotoxic and hematotoxic effects of occupational exposures," The toxic effects of environmental factors at work places on the hematopoietic and immune systems are of basic importance due to the time of exposure, lasting on average 8 hours daily during one week. Porphyrinurias and porphyrias have been observed after exposure to hexachlorobenzene, chlorinated dibenzodioxins, polychlorinated biphenyls, polybrominated biphenyls, vinyl chloride and lead. Aplastic anemia may occur after exposure to benzene, pesticides, arsenic, cadmium and copper compounds. Megaloblastic anemia has been noted in subjects exposed to arsenic, chlordane, benzene and nitrous oxide. Methemoglobinemia is induced by aromatic nitro and amino compounds. Hemolytic reactions caused by arsenic, methyl chloride, naphthalene, lead, cadmium and mercury compounds represent a separate problem. Immunodeficiencies resulting in decreased antitumor and antiinfectious immunity have been reported in subjects exposed to asbestos, ozone, dimethylsulphoxide, vinilidene chloride, and benzene homologues. Lymphocytopenia may be induced by manganese, lead, toluene and industrial noise. Neutropenia was marked after exposure to carbon disulphide, arsenic compounds, benzene and electromagnetic fields. Only a few reports concern the lymphocyte T3, T4 and T8 subpopulations. Electromagnetic fields (microwaves) cause an imbalance of that subpopulation, consisting of a decrease in the T8 cell count. The neutrophil enzymes, such as myeloperoxidase and alkaline phosphatase, decrease in their activity after exposure to polychlorinated biphenyls, carbon disulphide, chlorobenzene and DDT. A majority of agents cited include genotoxic effects reflected in chromosome aberrations and increased sister chromatid exchange and abnormal unscheduled DNA synthesis. Leukemia or lymphoma risk is increased after exposure to pesticides, electromagnetic fields, benzene and irradiation.","Immunotoxic and hematotoxic effects of occupational exposuresAbs: The toxic effects of environmental factors at work places on the hematopoietic and immune systems are of basic importance due to the time of exposure, lasting on average 8 hours daily during one week. Porphyrinurias and porphyrias have been observed after exposure to hexachlorobenzene, chlorinated dibenzodioxins, polychlorinated biphenyls, polybrominated biphenyls, vinyl chloride and lead. Aplastic anemia may occur after exposure to benzene, pesticides, arsenic, cadmium and copper compounds. Megaloblastic anemia has been noted in subjects exposed to arsenic, chlordane, benzene and nitrous oxide. Methemoglobinemia is induced by aromatic nitro and amino compounds. Hemolytic reactions caused by arsenic, methyl chloride, naphthalene, lead, cadmium and mercury compounds represent a separate problem. Immunodeficiencies resulting in decreased antitumor and antiinfectious immunity have been reported in subjects exposed to asbestos, ozone, dimethylsulphoxide, vinilidene chloride, and benzene homologues. Lymphocytopenia may be induced by manganese, lead, toluene and industrial noise. Neutropenia was marked after exposure to carbon disulphide, arsenic compounds, benzene and electromagnetic fields. Only a few reports concern the lymphocyte T3, T4 and T8 subpopulations. Electromagnetic fields (microwaves) cause an imbalance of that subpopulation, consisting of a decrease in the T8 cell count. The neutrophil enzymes, such as myeloperoxidase and alkaline phosphatase, decrease in their activity after exposure to polychlorinated biphenyls, carbon disulphide, chlorobenzene and DDT. A majority of agents cited include genotoxic effects reflected in chromosome aberrations and increased sister chromatid exchange and abnormal unscheduled DNA synthesis. Leukemia or lymphoma risk is increased after exposure to pesticides, electromagnetic fields, benzene and irradiation."
147,Rodriquez et al. 1998,Effects of oral exposure to mining waste on in vivo dopamine release from rat striatum," #Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Pat, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an anima model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/mu l) when compared to a control group (113.7 +/- 14.3 pg/mu l). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/mu l versus control group 21.7 +/- 5.8 pg/mu l). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Out results indicate that this mining waste may represent a health risk for the exposed population.","Effects of oral exposure to mining waste on in vivo dopamine release from rat striatumAbs: #Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Pat, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an anima model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/mu l) when compared to a control group (113.7 +/- 14.3 pg/mu l). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/mu l versus control group 21.7 +/- 5.8 pg/mu l). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Out results indicate that this mining waste may represent a health risk for the exposed population."
148,Tollestrup et al. 1995,Mortality in a cohort of orchard workers exposed to lead arsenate pesticide spray," #During the period from 1890 to 1940, lead arsenate was the major pesticide used in apple orchards to control the coddling moth. In the Wenatchee area of Washington State, lead arsenate spray was used for longer periods and in larger quantities than in other areas of the United States. In 1938, a cohort of 1,231 people who lived in this area was selected for a study to determine the effects of exposure to lead arsenate spray and residue. This same cohort was re-examined to determine whether there was excess mortality that could be attributed to the lead arsenate exposure. Three levels of exposure (i.e., orchardist, intermediate, consumer) were defined, based upon the use of lead arsenate pesticide spray before and during the 1938 apple growing season. Age-adjusted hazard ratios for all causes of mortality were elevated for both male orchardists and male intermediates. The only significantly increased age-adjusted hazard ratio (1.94) was heart disease in male intermediates. No significantly elevated age-adjusted hazard ratios were observed for women in any exposure group. The lack of evidence that supported an increase in mortality from respiratory cancer in this cohort may have resulted from the lower cumulative concentration of arsenic exposure, the type of arsenical compound, and the small number of study subjects.","Mortality in a cohort of orchard workers exposed to lead arsenate pesticide sprayAbs: #During the period from 1890 to 1940, lead arsenate was the major pesticide used in apple orchards to control the coddling moth. In the Wenatchee area of Washington State, lead arsenate spray was used for longer periods and in larger quantities than in other areas of the United States. In 1938, a cohort of 1,231 people who lived in this area was selected for a study to determine the effects of exposure to lead arsenate spray and residue. This same cohort was re-examined to determine whether there was excess mortality that could be attributed to the lead arsenate exposure. Three levels of exposure (i.e., orchardist, intermediate, consumer) were defined, based upon the use of lead arsenate pesticide spray before and during the 1938 apple growing season. Age-adjusted hazard ratios for all causes of mortality were elevated for both male orchardists and male intermediates. The only significantly increased age-adjusted hazard ratio (1.94) was heart disease in male intermediates. No significantly elevated age-adjusted hazard ratios were observed for women in any exposure group. The lack of evidence that supported an increase in mortality from respiratory cancer in this cohort may have resulted from the lower cumulative concentration of arsenic exposure, the type of arsenical compound, and the small number of study subjects."
149,Hopenhayn-Rich et al. 1996,Bladder cancer mortality associated with arsenic in drinking water in Argentina," Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan.","Bladder cancer mortality associated with arsenic in drinking water in ArgentinaAbs: Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan."
150,Mann et al. 1996,A physiologically based pharmacokinetic model for arsenic exposure: I. Development in hamsters and rabbits," A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues andin vitromeasurements of the tissue affinity constants are discussed.","A physiologically based pharmacokinetic model for arsenic exposure: I. Development in hamsters and rabbitsAbs: A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues andin vitromeasurements of the tissue affinity constants are discussed."
151,Chen et al. 1996,Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposure," The cardiovascular effects of inorganic arsenic have been documented, but the dose-response relationship between ischemic heart disease (ISHD) and long-term arsenic exposure remains to be elucidated. Mortality rates from ISHD among residents in 60 villages of the area in Taiwan with endemic arseniasis from 1973 through 1986 were analyzed to examine their association with arsenic concentration in drinking water. Based on 1 355 915 person-years and 217 ISHD deaths, the cumulative ISHD mortalities from birth to age 79 years were 3.4%, 3.5%, 4.7%, and 6.6%, respectively, for residents who lived in villages in which the median arsenic concentrations in drinking water were <0.1, 0.1 to 0.34, 0.35 to 0.59, and 0.6 mg/L. A cohort of 263 patients affected with blackfoot disease (BFD), a unique arsenic-related peripheral vascular disease, and 2293 non-BFD residents in the endemic area of arseniasis were recruited and followed up for an average period of 5.0 years. There was a monotonous biological gradient relationship between cumulative arsenic exposure through drinking artesian well water and ISHD mortality. The relative risks were 2.5, 4.0, and 6.5, respectively, for those who had a cumulative arsenic exposure of 0.1 to 9.9, 10.0 to 19.9, and 20.0 mg/L-years compared with those without the arsenic exposure after adjustment for age, sex, cigarette smoking, body mass index, serum cholesterol and triglyceride levels, and disease status for hypertension and diabetes through proportional-hazards regression analysis. BFD patients were found to have a significantly higher ISHD mortality than non-BFD residents, showing a multivariate-adjusted relative risk of 2.5 (95% CI, 1.1 to 5.4).","Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposureAbs: The cardiovascular effects of inorganic arsenic have been documented, but the dose-response relationship between ischemic heart disease (ISHD) and long-term arsenic exposure remains to be elucidated. Mortality rates from ISHD among residents in 60 villages of the area in Taiwan with endemic arseniasis from 1973 through 1986 were analyzed to examine their association with arsenic concentration in drinking water. Based on 1 355 915 person-years and 217 ISHD deaths, the cumulative ISHD mortalities from birth to age 79 years were 3.4%, 3.5%, 4.7%, and 6.6%, respectively, for residents who lived in villages in which the median arsenic concentrations in drinking water were <0.1, 0.1 to 0.34, 0.35 to 0.59, and 0.6 mg/L. A cohort of 263 patients affected with blackfoot disease (BFD), a unique arsenic-related peripheral vascular disease, and 2293 non-BFD residents in the endemic area of arseniasis were recruited and followed up for an average period of 5.0 years. There was a monotonous biological gradient relationship between cumulative arsenic exposure through drinking artesian well water and ISHD mortality. The relative risks were 2.5, 4.0, and 6.5, respectively, for those who had a cumulative arsenic exposure of 0.1 to 9.9, 10.0 to 19.9, and 20.0 mg/L-years compared with those without the arsenic exposure after adjustment for age, sex, cigarette smoking, body mass index, serum cholesterol and triglyceride levels, and disease status for hypertension and diabetes through proportional-hazards regression analysis. BFD patients were found to have a significantly higher ISHD mortality than non-BFD residents, showing a multivariate-adjusted relative risk of 2.5 (95% CI, 1.1 to 5.4)."
152,Hopenhayn-Rich et al. 1996,Methylation study of a population environmentally exposed to arsenic in drinking water," Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.","Methylation study of a population environmentally exposed to arsenic in drinking waterAbs: Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear."
153,Arrighi et al. 1996,Controlling the healthy worker survivor effect: an example of arsenic exposure and respiratory cancer," <strong>OBJECTIVE: </strong>This investigation sought to examine whether methods proposed to control the healthy worker survivor effect would influence the shape or magnitude of the dose-response curve for respiratory cancer induced by arsenic.<br /><br /><strong>METHODS: </strong>Results from an unadjusted analysis are compared with results obtained by applying four different methods for control of the healthy worker survivor effect to data on arsenic exposure and respiratory cancer. The four methods are: exposure lag, adjustment for work status, cohort restriction, and the G null test.<br /><br /><strong>RESULTS: </strong>Cohort restriction gave erratic results depending upon the minimum years of follow up used. Exposure lag substantially increased the rate ratios and a non-linear shape (decreasing slope) compared with an unlagged analysis. Adjusting for work status (currently employed upsilon retired or otherwise not employed) yielded slightly higher rate ratios than an unadjusted analysis, with an overall shape similar to the baseline analysis. Results from the G null test procedure of Robins (1986), although not directly comparable with the baseline analysis, did show an adverse effect of exposure that seemed to reach a maximum when exposure was lagged between 10 and 20 years.<br /><br /><strong>CONCLUSIONS: </strong>All results confirm an adverse effect of arsenic exposure on respiratory cancer. In these data, it seems that the healthy worker survivor effect was not strong enough to mask the strong effect of arsenic exposure on respiratory cancer. Nevertheless, several methods show a stronger association between arsenic exposure and respiratory cancer after adjustment for the healthy worker survivor effect, suggesting that for weaker causal associations, studies not controlling for this source of bias will have low power to detect results. Although the G methods are theoretically the most unbiased, further work elucidating the validity of the assumptions underlying lagging, adjustment for work status, and the G methods are needed before clear recommendations can be made.","Controlling the healthy worker survivor effect: an example of arsenic exposure and respiratory cancerAbs: <strong>OBJECTIVE: </strong>This investigation sought to examine whether methods proposed to control the healthy worker survivor effect would influence the shape or magnitude of the dose-response curve for respiratory cancer induced by arsenic.<br /><br /><strong>METHODS: </strong>Results from an unadjusted analysis are compared with results obtained by applying four different methods for control of the healthy worker survivor effect to data on arsenic exposure and respiratory cancer. The four methods are: exposure lag, adjustment for work status, cohort restriction, and the G null test.<br /><br /><strong>RESULTS: </strong>Cohort restriction gave erratic results depending upon the minimum years of follow up used. Exposure lag substantially increased the rate ratios and a non-linear shape (decreasing slope) compared with an unlagged analysis. Adjusting for work status (currently employed upsilon retired or otherwise not employed) yielded slightly higher rate ratios than an unadjusted analysis, with an overall shape similar to the baseline analysis. Results from the G null test procedure of Robins (1986), although not directly comparable with the baseline analysis, did show an adverse effect of exposure that seemed to reach a maximum when exposure was lagged between 10 and 20 years.<br /><br /><strong>CONCLUSIONS: </strong>All results confirm an adverse effect of arsenic exposure on respiratory cancer. In these data, it seems that the healthy worker survivor effect was not strong enough to mask the strong effect of arsenic exposure on respiratory cancer. Nevertheless, several methods show a stronger association between arsenic exposure and respiratory cancer after adjustment for the healthy worker survivor effect, suggesting that for weaker causal associations, studies not controlling for this source of bias will have low power to detect results. Although the G methods are theoretically the most unbiased, further work elucidating the validity of the assumptions underlying lagging, adjustment for work status, and the G methods are needed before clear recommendations can be made."
154,Bagla and Kaiser 1996,India's spreading health crisis draws global arsenic experts," New Delhi--A potentially devastating health crisis is quietly unfolding in West Bengal, India, where high levels of arsenic have leached into well water and have put more than a million Indians at risk. The immense scale of the human tragedy has begun to attract the attention of scientists from around the world, who see in this grim event an unprecedented chance to learn more about the health effects of arsenic, a known carcinogen. ""We're talking about numbers [of arsenic-poisoning victims] that have never been seen before in the world,"" says University of California, Berkeley, epidemiologist Allan Smith.","India's spreading health crisis draws global arsenic expertsAbs: New Delhi--A potentially devastating health crisis is quietly unfolding in West Bengal, India, where high levels of arsenic have leached into well water and have put more than a million Indians at risk. The immense scale of the human tragedy has begun to attract the attention of scientists from around the world, who see in this grim event an unprecedented chance to learn more about the health effects of arsenic, a known carcinogen. ""We're talking about numbers [of arsenic-poisoning victims] that have never been seen before in the world,"" says University of California, Berkeley, epidemiologist Allan Smith."
155,Garland et al. 1996,Toenail trace element levels and breast cancer: a prospective study," The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62, 641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66-1.91); for copper, 0.91 (95% CI 0.59-1.42); for chromium, 0.96 (95% Cl 0.61-1.52); for iron, 0.89 (95% CI 0.56-1.40); and for zinc, 1.09 (95% CI 0.70-1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% Cl 0.87-3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk.","Toenail trace element levels and breast cancer: a prospective studyAbs: The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62, 641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66-1.91); for copper, 0.91 (95% CI 0.59-1.42); for chromium, 0.96 (95% Cl 0.61-1.52); for iron, 0.89 (95% CI 0.56-1.40); and for zinc, 1.09 (95% CI 0.70-1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% Cl 0.87-3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk."
156,Byrd et al. 1996,Carcinogenic risks of inorganic arsenic in perspective," Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.","Carcinogenic risks of inorganic arsenic in perspectiveAbs: Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate."
157,Goossens et al. 1993,Elimination of interferences in the determination of arsenic and selenium in biological samples by inductively coupled plasma mass spectrometry," A study of both spectral and nonspectral interferences was made in the determination of arsenic (7440382) (As) and selenium (7782492) (Se). The merits of internal standardization and standard addition in correction for matrix effects were compared. Spectral interferences on arsenic and selenium were dealt with by a new approach. The addition of appropriate amounts of ethanol in combination with nebulizer gas adjustment allowed polyatomic interferences up to 50 times higher than the genuine As+ and Se+ signals to be eliminated completely. This combination of chemical modification with nebulizer gas flow rate adjustment allowed arsenic and selenium to be accurately determined in chlorine matrices. The method used a minimum of sample pretreatment and therefore was easy to apply in routine analysis. Standard addition as a calibration method permitted the accurate determination of arsenic and selenium in biological samples, including serum and urine.","Elimination of interferences in the determination of arsenic and selenium in biological samples by inductively coupled plasma mass spectrometryAbs: A study of both spectral and nonspectral interferences was made in the determination of arsenic (7440382) (As) and selenium (7782492) (Se). The merits of internal standardization and standard addition in correction for matrix effects were compared. Spectral interferences on arsenic and selenium were dealt with by a new approach. The addition of appropriate amounts of ethanol in combination with nebulizer gas adjustment allowed polyatomic interferences up to 50 times higher than the genuine As+ and Se+ signals to be eliminated completely. This combination of chemical modification with nebulizer gas flow rate adjustment allowed arsenic and selenium to be accurately determined in chlorine matrices. The method used a minimum of sample pretreatment and therefore was easy to apply in routine analysis. Standard addition as a calibration method permitted the accurate determination of arsenic and selenium in biological samples, including serum and urine."
158,Englyst et al. 2001,Lung cancer risks among lead smelter workers also exposed to arsenic," Recent publications indicate an increased incidence of lung cancer in non-ferrous smelter workers exposed to lead. The present study provides further data on selected subgroups in one such cohort. The cohort was based on 3979 smelter workers employed for at least 1 year between 1928 and 1979, and also exposed to lead and included in the Blood Lead Register that was started at the smelter in 1950. Two subcohorts were formed from the original cohort. One consists of 710 workers employed at the lead departments (Lead subcohort 1), and the other of 383 workers employed at the lead departments (Lead subcohort 2), but never at other works where an excess lung cancer risk was previously identified. Standardized Cancer Incidence Rates (SIR) 1958-1987 were calculated relative to county rates. In the subcohorts, arsenic exposure in lung cancer cases was assessed in detail based on occupational hygiene information from the company. Lung cancer incidence was raised in both subcohorts (Lead subcohort 1: SIR 2.4; 95% CI 1.2-4.5; Lead subcohort 2: SIR 3.6; 95% CI 1.2-8.3). Total cancer incidence in the cohorts was not increased. A detailed study of arsenic exposure in the 10 lung cancer cases in these two subcohorts revealed that all but one of these cases had a significant exposure also to arsenic. An elevated incidence of lung cancer was observed in smelter workers exposed to lead. However, considerable arsenic exposure also occurred in a majority of the lung cancer cases in the investigated subcohorts. In this multifactorial exposure situation it has not been possible to separate the carcinogenic effects of lead and arsenic, but a possible interaction between these metals may be involved in explaining the carcinogenic risks.","Lung cancer risks among lead smelter workers also exposed to arsenicAbs: Recent publications indicate an increased incidence of lung cancer in non-ferrous smelter workers exposed to lead. The present study provides further data on selected subgroups in one such cohort. The cohort was based on 3979 smelter workers employed for at least 1 year between 1928 and 1979, and also exposed to lead and included in the Blood Lead Register that was started at the smelter in 1950. Two subcohorts were formed from the original cohort. One consists of 710 workers employed at the lead departments (Lead subcohort 1), and the other of 383 workers employed at the lead departments (Lead subcohort 2), but never at other works where an excess lung cancer risk was previously identified. Standardized Cancer Incidence Rates (SIR) 1958-1987 were calculated relative to county rates. In the subcohorts, arsenic exposure in lung cancer cases was assessed in detail based on occupational hygiene information from the company. Lung cancer incidence was raised in both subcohorts (Lead subcohort 1: SIR 2.4; 95% CI 1.2-4.5; Lead subcohort 2: SIR 3.6; 95% CI 1.2-8.3). Total cancer incidence in the cohorts was not increased. A detailed study of arsenic exposure in the 10 lung cancer cases in these two subcohorts revealed that all but one of these cases had a significant exposure also to arsenic. An elevated incidence of lung cancer was observed in smelter workers exposed to lead. However, considerable arsenic exposure also occurred in a majority of the lung cancer cases in the investigated subcohorts. In this multifactorial exposure situation it has not been possible to separate the carcinogenic effects of lead and arsenic, but a possible interaction between these metals may be involved in explaining the carcinogenic risks."
159,Hwang et al. 1997,Environmental arsenic exposure of children around a former copper smelter site," Arsenic residues in the communities surrounding former smelters remain a public health concern, especially for infants and children. To evaluate environmental exposure among these children, a population-based cross-sectional study was conducted in the vicinity of a former copper smelter in Anaconda, Montana. A total of 414 children less than 72 months old were recruited. First morning voided urine samples and environmental samples were collected for arsenic measurements. The geometric mean of speciated urinary arsenic was 8.6 microg/liter (GSD = 1.7, N = 289). Average arsenic levels of different types of soil ranged from 121 to 236 microg/g and were significantly related to proximity and wind direction to the smelter site. The same significant relationship was observed for interior dust arsenic. Speciated urinary arsenic was found to be significantly related to soil arsenic in bare areas in residential yards (P < 0.0005). In general, elevated excretion of arsenic was demonstrable and warranted parents' attention to reduce exposure of their children to environmental arsenic.","Environmental arsenic exposure of children around a former copper smelter siteAbs: Arsenic residues in the communities surrounding former smelters remain a public health concern, especially for infants and children. To evaluate environmental exposure among these children, a population-based cross-sectional study was conducted in the vicinity of a former copper smelter in Anaconda, Montana. A total of 414 children less than 72 months old were recruited. First morning voided urine samples and environmental samples were collected for arsenic measurements. The geometric mean of speciated urinary arsenic was 8.6 microg/liter (GSD = 1.7, N = 289). Average arsenic levels of different types of soil ranged from 121 to 236 microg/g and were significantly related to proximity and wind direction to the smelter site. The same significant relationship was observed for interior dust arsenic. Speciated urinary arsenic was found to be significantly related to soil arsenic in bare areas in residential yards (P < 0.0005). In general, elevated excretion of arsenic was demonstrable and warranted parents' attention to reduce exposure of their children to environmental arsenic."
160,Akland et al. 1997,An interagency partnership applied to the study of environmental health in the lower Rio Grande Valley of Texas," BIOSIS COPYRIGHT: BIOL ABS. An environmental monitoring investigation was initiated in the Lower Rio Grande Valley in response to concerns about the potential link between local residents' health and environmental pollution. Concerns expressed by residents of the community related to industrial emissions, agricultural pesticide use, and inadequate infrastructure. A field investigation was conducted jointly by the U.S. Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention (CDC), and the State of Texas during two sampling periods in 1993. The results provided preliminary data about the levels, sources, and pathways of actual human exposure in the Valley. Samples of indoor and outdoor air, house dust, soil, food, drinking water, urine, blood, and breath were collected and analyzed for several compound classes. This paper presents an overview of the study including the study design, the survey methods, participant selection, and communication of the results. This projec","An interagency partnership applied to the study of environmental health in the lower Rio Grande Valley of TexasAbs: BIOSIS COPYRIGHT: BIOL ABS. An environmental monitoring investigation was initiated in the Lower Rio Grande Valley in response to concerns about the potential link between local residents' health and environmental pollution. Concerns expressed by residents of the community related to industrial emissions, agricultural pesticide use, and inadequate infrastructure. A field investigation was conducted jointly by the U.S. Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention (CDC), and the State of Texas during two sampling periods in 1993. The results provided preliminary data about the levels, sources, and pathways of actual human exposure in the Valley. Samples of indoor and outdoor air, house dust, soil, food, drinking water, urine, blood, and breath were collected and analyzed for several compound classes. This paper presents an overview of the study including the study design, the survey methods, participant selection, and communication of the results. This projec"
161,Granero et al. 1998,"Biological monitoring of environmental pollution and human exposure to metals in Tarragona, Spain I levels in hair of school children"," BIOSIS COPYRIGHT: BIOL ABS. Hair samples of 124 school children (11-13 years old) living in 3 residential areas in the neighborhood of a hazardous waste incinerator (HWI) now under construction (Tarragona, Spain) were analyzed for arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl), and vanadium (V) concentrations by ICP-MS. Beryllium, Tl, and V levels were under the respective detection limits. The concentrations (mug/g) of the remaining 8 elements showed the following ranges: 0.01-0.10 for As, 0.03-0.73 for Cd, 0.13-3.23 for Cr, 0.09-2.54 for Hg, 0.04-0.99 for Mn, 0.10-3.18 for Ni, 0.38-23.83 for Pb, and 0.01-2.80 for Sn. No differences in relation to sex were observed. By contrast, significant differences with respect to the place of residence were found in the hair concentrations of As, Cd, Cr, Hg, and Sn. In general terms, the current metal levels in hair of school children are of the same order of magnitude","Biological monitoring of environmental pollution and human exposure to metals in Tarragona, Spain I levels in hair of school childrenAbs: BIOSIS COPYRIGHT: BIOL ABS. Hair samples of 124 school children (11-13 years old) living in 3 residential areas in the neighborhood of a hazardous waste incinerator (HWI) now under construction (Tarragona, Spain) were analyzed for arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl), and vanadium (V) concentrations by ICP-MS. Beryllium, Tl, and V levels were under the respective detection limits. The concentrations (mug/g) of the remaining 8 elements showed the following ranges: 0.01-0.10 for As, 0.03-0.73 for Cd, 0.13-3.23 for Cr, 0.09-2.54 for Hg, 0.04-0.99 for Mn, 0.10-3.18 for Ni, 0.38-23.83 for Pb, and 0.01-2.80 for Sn. No differences in relation to sex were observed. By contrast, significant differences with respect to the place of residence were found in the hair concentrations of As, Cd, Cr, Hg, and Sn. In general terms, the current metal levels in hair of school children are of the same order of magnitude"
162,Wingren and Axelson 1987,Mortality in the Swedish glassworks industry," An earlier, relatively small case-referent study has shown an increased risk for glassworks employees to die from stomach cancer, lung cancer, and cardiovascular disorders. This observation suggested an extended study virtually covering the entire glass-producing industry of Sweden. This new study confirmed the earlier results and, furthermore, an excess risk for colon cancer was also identified. No deviation was found in the cancer mortality pattern for all men in the glass-producing area compared to the whole of Sweden. The grouping of glassworks employees according to type of metal consumption at the glassworks showed the excess risks of stomach cancer, colon cancer, and cardiovascular deaths to relate to glassworks with a high consumption of lead, arsenic, antimony, and manganese. However, the strong correlation of these various metal exposures did not permit any successful separation of the effects of the different metals. For cardiovascular mortality, as for cancer, the glassblowers especially suffered from increased risk. Their exposure might, to a great extent, be oral, involving the glassblower's pipe as a ""vector"" for the exposure to various metals.","Mortality in the Swedish glassworks industryAbs: An earlier, relatively small case-referent study has shown an increased risk for glassworks employees to die from stomach cancer, lung cancer, and cardiovascular disorders. This observation suggested an extended study virtually covering the entire glass-producing industry of Sweden. This new study confirmed the earlier results and, furthermore, an excess risk for colon cancer was also identified. No deviation was found in the cancer mortality pattern for all men in the glass-producing area compared to the whole of Sweden. The grouping of glassworks employees according to type of metal consumption at the glassworks showed the excess risks of stomach cancer, colon cancer, and cardiovascular deaths to relate to glassworks with a high consumption of lead, arsenic, antimony, and manganese. However, the strong correlation of these various metal exposures did not permit any successful separation of the effects of the different metals. For cardiovascular mortality, as for cancer, the glassblowers especially suffered from increased risk. Their exposure might, to a great extent, be oral, involving the glassblower's pipe as a ""vector"" for the exposure to various metals."
163,Katsouyanni and Pershagen 1997,Ambient air pollution exposure and cancer," BIOSIS COPYRIGHT: BIOL ABS. Epidemiologic evidence on the relation between ambient air pollution exposure and cancer is reviewed. The well-documented urban/rural difference in lung cancer incidence and the detection of known carcinogens in the atmosphere gave rise to the hypothesis that long-term exposure to air pollution may have an effect on lung cancer risk. However, problems inherent in assessing adequately the exposure of interest led to considerable difficulties in evaluating this effect. Routinely measured air pollutants do not include, as a rule, established carcinogens, and air pollution measurements usually come from fixed-site monitors, making it difficult to estimate individual exposures, especially long-term. The nature of the exposure and associated measurement problems made ecologic comparisons a natural way to approach the study of air pollution effects on lung cancer risk. The descriptive/ecologic studies which have been undertaken after 1950 often had problems with inadequate con","Ambient air pollution exposure and cancerAbs: BIOSIS COPYRIGHT: BIOL ABS. Epidemiologic evidence on the relation between ambient air pollution exposure and cancer is reviewed. The well-documented urban/rural difference in lung cancer incidence and the detection of known carcinogens in the atmosphere gave rise to the hypothesis that long-term exposure to air pollution may have an effect on lung cancer risk. However, problems inherent in assessing adequately the exposure of interest led to considerable difficulties in evaluating this effect. Routinely measured air pollutants do not include, as a rule, established carcinogens, and air pollution measurements usually come from fixed-site monitors, making it difficult to estimate individual exposures, especially long-term. The nature of the exposure and associated measurement problems made ecologic comparisons a natural way to approach the study of air pollution effects on lung cancer risk. The descriptive/ecologic studies which have been undertaken after 1950 often had problems with inadequate con"
164,Kristiansen et al. 1997,Toxic trace element reference levels in blood and urine: influence of gender and lifestyle factors," This study is part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues) which aims at establishing reference intervals for trace elements in blood, urine and other human tissues. In this study, reference intervals (0.05-0.95 fractiles) were estimated for lead in blood (105-529 nmol/l for men, 80-340 nmol/l for women), manganese in blood (100-271 nmol/l) and arsenic in urine (36-541 nmol/l for men, 21-475 nmol/l for women). Upper reference limits (0.95 fractile) were established for chromium in urine (13 nmol/l), nickel in urine (52 nmol/l) and cobalt in urine (23 nmol/l for men, 31 nmol/l for women). The reference group was a Danish subpopulation (n = 189), age 40-70 years. The influence of gender, age, health status parameters, nutrition and various lifestyle factors was investigated. Urinary arsenic and blood lead levels were found to be higher for men than for women. Arsenic levels also increased with age up to 60 years, and then decreased. Alcohol intake lead to increased arsenic levels in urine as well as blood lead levels. Urinary nickel levels were higher in persons frequently eating porridge and porridge oats.","Toxic trace element reference levels in blood and urine: influence of gender and lifestyle factorsAbs: This study is part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues) which aims at establishing reference intervals for trace elements in blood, urine and other human tissues. In this study, reference intervals (0.05-0.95 fractiles) were estimated for lead in blood (105-529 nmol/l for men, 80-340 nmol/l for women), manganese in blood (100-271 nmol/l) and arsenic in urine (36-541 nmol/l for men, 21-475 nmol/l for women). Upper reference limits (0.95 fractile) were established for chromium in urine (13 nmol/l), nickel in urine (52 nmol/l) and cobalt in urine (23 nmol/l for men, 31 nmol/l for women). The reference group was a Danish subpopulation (n = 189), age 40-70 years. The influence of gender, age, health status parameters, nutrition and various lifestyle factors was investigated. Urinary arsenic and blood lead levels were found to be higher for men than for women. Arsenic levels also increased with age up to 60 years, and then decreased. Alcohol intake lead to increased arsenic levels in urine as well as blood lead levels. Urinary nickel levels were higher in persons frequently eating porridge and porridge oats."
165,Bulbulyan et al. 1996,Mortality in a cohort of Russian fertilizer workers," OBJECTIVES. The study evaluated the mortality of workers exposed to precursors of N-nitroso compounds in a Russian fertilizer plant. METHODS. Workers employed at least two years between 1945 and 1985 in production departments or other services were included in the cohort, which comprised 2039 men and 2957 women followed from 1965 to 1990. The standardized mortality ratios (SMR) were calculated using cause-specific death rates for the Moscow region as reference. An internal comparison was carried out using Poisson regression modeling. Exposure to arsenic, nitrogen oxides, and sulfur dioxide was estimated from an industrial hygiene survey. RESULTS. The production and other workers had no excess of mortality from all causes or all neoplasms. However the male production workers had excess mortality from all cancers combined (SMR 143) and lung cancer (SMR 186) after a latency period of > or = 20 years. Men with the highest exposure to nitrogen oxides had a twofold increase in mortality from stomach cancer, with a marginally significant increasing trend between stomach cancer and cumulative exposure to nitrogen oxides for both genders. Excess mortality from all cancers and stomach cancer was found for the worker with the highest average exposure to arsenic, and excess lung cancer mortality could be attributed to exposure to arsenic. CONCLUSIONS. The investigation showed a weak association between employment in a fertilizer production plant and increased mortality from cancer. The results somewhat support the hypothesis that occupational exposure to precursors of N-nitroso compounds increases the risk of stomach cancer mortality, as does exposure to arsenic.","Mortality in a cohort of Russian fertilizer workersAbs: OBJECTIVES. The study evaluated the mortality of workers exposed to precursors of N-nitroso compounds in a Russian fertilizer plant. METHODS. Workers employed at least two years between 1945 and 1985 in production departments or other services were included in the cohort, which comprised 2039 men and 2957 women followed from 1965 to 1990. The standardized mortality ratios (SMR) were calculated using cause-specific death rates for the Moscow region as reference. An internal comparison was carried out using Poisson regression modeling. Exposure to arsenic, nitrogen oxides, and sulfur dioxide was estimated from an industrial hygiene survey. RESULTS. The production and other workers had no excess of mortality from all causes or all neoplasms. However the male production workers had excess mortality from all cancers combined (SMR 143) and lung cancer (SMR 186) after a latency period of > or = 20 years. Men with the highest exposure to nitrogen oxides had a twofold increase in mortality from stomach cancer, with a marginally significant increasing trend between stomach cancer and cumulative exposure to nitrogen oxides for both genders. Excess mortality from all cancers and stomach cancer was found for the worker with the highest average exposure to arsenic, and excess lung cancer mortality could be attributed to exposure to arsenic. CONCLUSIONS. The investigation showed a weak association between employment in a fertilizer production plant and increased mortality from cancer. The results somewhat support the hypothesis that occupational exposure to precursors of N-nitroso compounds increases the risk of stomach cancer mortality, as does exposure to arsenic."
166,Wulff et al. 1996,Cancer incidence for children born in a smelting community," The Ronnskar smelter in Skelleftea, Sweden, produces significant environmental pollutants, such as lead, arsenic, copper, cadmium and sulphur dioxide. The purpose of the present study was to determine whether children born to women living near the smelter during pregnancy had an increased risk of childhood cancer. The study group consisted of children born between 1961 and 1990 in the municipality of Skelleftea and parish of Holmsund. Through linkage to the Swedish Cancer Registry cancer diagnoses in the study group were obtained and compared with the expected ones based on the national incidence rates. Thirteen cases of childhood cancer were identified among children born in the vicinity of the smelter against 6.7 expected (SIR 195, 95%CI 88-300). Among distant born the observed number of cases (n = 42) was similar to that expected (n = 41.8).","Cancer incidence for children born in a smelting communityAbs: The Ronnskar smelter in Skelleftea, Sweden, produces significant environmental pollutants, such as lead, arsenic, copper, cadmium and sulphur dioxide. The purpose of the present study was to determine whether children born to women living near the smelter during pregnancy had an increased risk of childhood cancer. The study group consisted of children born between 1961 and 1990 in the municipality of Skelleftea and parish of Holmsund. Through linkage to the Swedish Cancer Registry cancer diagnoses in the study group were obtained and compared with the expected ones based on the national incidence rates. Thirteen cases of childhood cancer were identified among children born in the vicinity of the smelter against 6.7 expected (SIR 195, 95%CI 88-300). Among distant born the observed number of cases (n = 42) was similar to that expected (n = 41.8)."
167,Privalova et al. 2001,Some considerations concerning multimedia-multipollutant risk assessment methodology: use of epidemiologic data for non-cancer risk assessment in Russia," #The highly industrialized small town of Verkhnyaya Pyshma (in the Urals region of Russia) was chosen as the site of a multimedia-multipollutant risk assessment using the U.S. Environmental Protection Agency methodology. The assessment was based on routine environmental pollution monitoring data for ambient air, soils, drinking water, and food, and the international environmental epidemiology literature. Using an a priori set of the preliminary health-based criteria, we selected nine pollutants for risk assessment: total suspended particles (TSP), sulfur dioxide, nitrogen dioxide, benzo(a)pyrene (BaP), ammonia arsenic, copper, cadmium, and lead. We used dose-response functions derived from epidemiologic studies to assess individual and population risks for TSP, SO2, NO2, As, Cd, and Pb. We assessed both cancer (for BaP, As, and Cd) and non-cancer (for all the chosen pollutants but BaP) responses, but in this paper we discuss only the assessments of noncarcinogenic risks due to TSP, SO2, NO2, Pb, and Cd as examples of how the quantitative estimates of health effects can be produced by using a risk function approach. We also schematically present a modified conceptual model of multimedia-multipollutant risk assessment taking into account the experience gained with this study.","Some considerations concerning multimedia-multipollutant risk assessment methodology: use of epidemiologic data for non-cancer risk assessment in RussiaAbs: #The highly industrialized small town of Verkhnyaya Pyshma (in the Urals region of Russia) was chosen as the site of a multimedia-multipollutant risk assessment using the U.S. Environmental Protection Agency methodology. The assessment was based on routine environmental pollution monitoring data for ambient air, soils, drinking water, and food, and the international environmental epidemiology literature. Using an a priori set of the preliminary health-based criteria, we selected nine pollutants for risk assessment: total suspended particles (TSP), sulfur dioxide, nitrogen dioxide, benzo(a)pyrene (BaP), ammonia arsenic, copper, cadmium, and lead. We used dose-response functions derived from epidemiologic studies to assess individual and population risks for TSP, SO2, NO2, As, Cd, and Pb. We assessed both cancer (for BaP, As, and Cd) and non-cancer (for all the chosen pollutants but BaP) responses, but in this paper we discuss only the assessments of noncarcinogenic risks due to TSP, SO2, NO2, Pb, and Cd as examples of how the quantitative estimates of health effects can be produced by using a risk function approach. We also schematically present a modified conceptual model of multimedia-multipollutant risk assessment taking into account the experience gained with this study."
168,Lubin et al. 2000,Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-up," Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m3-year was 0.21/(mg/m3-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure.","Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-upAbs: Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m3-year was 0.21/(mg/m3-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure."
169,Jarup et al. 1989,Cumulative arsenic exposure and lung cancer in smelter workers: a dose-response study," The cause-specific mortality was followed through 1981 in a cohort of 3,916 male Swedish smelter workers employed for at least 3 months from 1928 through 1967. Arsenic levels in the air of all workplaces within the smelter were estimated for three different time periods. Using this exposure matrix and detailed information of the work history, cumulative arsenic exposure could be computed for each worker. Standardized mortality ratios (SMRs) were calculated for several dose categories using age-specific mortality rates from the county where the smelter was situated. A positive dose-response relationship was found between cumulative arsenic exposure and lung cancer mortality with an overall SMR of 372 (304-450, 95% confidence interval). The lung cancer mortality was related to the estimated average intensity of exposure to arsenic but not to the duration. No positive dose-response relationship was found between arsenic and ischemic heart disease or cerebrovascular disease. There was also no evident dose-response relationship between estimated exposure to sulfur dioxide and lung cancer.","Cumulative arsenic exposure and lung cancer in smelter workers: a dose-response studyAbs: The cause-specific mortality was followed through 1981 in a cohort of 3,916 male Swedish smelter workers employed for at least 3 months from 1928 through 1967. Arsenic levels in the air of all workplaces within the smelter were estimated for three different time periods. Using this exposure matrix and detailed information of the work history, cumulative arsenic exposure could be computed for each worker. Standardized mortality ratios (SMRs) were calculated for several dose categories using age-specific mortality rates from the county where the smelter was situated. A positive dose-response relationship was found between cumulative arsenic exposure and lung cancer mortality with an overall SMR of 372 (304-450, 95% confidence interval). The lung cancer mortality was related to the estimated average intensity of exposure to arsenic but not to the duration. No positive dose-response relationship was found between arsenic and ischemic heart disease or cerebrovascular disease. There was also no evident dose-response relationship between estimated exposure to sulfur dioxide and lung cancer."
170,Englander et al. 1988,Mortality and cancer morbidity in workers exposed to sulphur dioxide in a sulphuric acid plant," To evaluate the risk of non-malignant respiratory disease and tumours at exposure to sulphur dioxide, a retrospective cohort study was performed on a group of 400 male workers, employed for at least six months during the period 1961-1981, in a sulphuric acid factory. Since 1969, fairly extensive measurements have been performed in the respiratory zone of the workers. The median level of total dust, over the years, was 2.2 mg/m3 (time-weighted average), of respirable dust 0.6 mg/m3, of sulphur dioxide 3.6 mg/m3, and of arsenic 11 micrograms/m3. There was a significantly increased total mortality in the period 1961-1985. Applying greater than or equal to 5 years latency period there were 47 observed deaths, giving a standardized mortality rate (SMR) of 1.57 (P = 0.002). The increased mortality was due to violence and intoxication (observed 9, SMR = 2.83; P = 0.006) and cardiovascular disease (SMR = 1.51, P = 0.05). The total tumour morbidity was not increased (observed 17, SMR = 1.17, P greater than 0.5) and there was no rise of either non-malignant or malignant lung diseases. However, there was an increase of bladder cancer (observed 5, SMR = 4.36, P = 0.006).","Mortality and cancer morbidity in workers exposed to sulphur dioxide in a sulphuric acid plantAbs: To evaluate the risk of non-malignant respiratory disease and tumours at exposure to sulphur dioxide, a retrospective cohort study was performed on a group of 400 male workers, employed for at least six months during the period 1961-1981, in a sulphuric acid factory. Since 1969, fairly extensive measurements have been performed in the respiratory zone of the workers. The median level of total dust, over the years, was 2.2 mg/m3 (time-weighted average), of respirable dust 0.6 mg/m3, of sulphur dioxide 3.6 mg/m3, and of arsenic 11 micrograms/m3. There was a significantly increased total mortality in the period 1961-1985. Applying greater than or equal to 5 years latency period there were 47 observed deaths, giving a standardized mortality rate (SMR) of 1.57 (P = 0.002). The increased mortality was due to violence and intoxication (observed 9, SMR = 2.83; P = 0.006) and cardiovascular disease (SMR = 1.51, P = 0.05). The total tumour morbidity was not increased (observed 17, SMR = 1.17, P greater than 0.5) and there was no rise of either non-malignant or malignant lung diseases. However, there was an increase of bladder cancer (observed 5, SMR = 4.36, P = 0.006)."
171,Enterline et al. 1987,"Some effects of cigarette smoking, arsenic, and SO2 on mortality among US copper smelter workers"," Previous studies of the relationship between arsenic levels and respiratory cancer among copper smelter workers have not directly accounted for possible effects of SO2 exposure and cigarette smoking. This is a report on the 1949-1980 mortality experience of 6,078 white male workers who worked at least 3 years between 1 January 1946 and 31 December 1976 at one or more of eight US copper smelters. The completeness of the cohort was verified statistically, and worker exposures to arsenic, SO2, dust, nickel, cadmium, and lead were estimated from retrospective industrial hygiene surveys reported elsewhere. By using internal controls, a dose-response relationship for lung cancer was observed with exposure to arsenic and SO2. When cigarette smoking data were included with arsenic and SO2 exposure data in a nested case-control analysis, only smoking and arsenic were statistically significant factors. The arsenic-lung cancer relationship was confined to a single smelter associated with high content feed. In the remaining smelters mortality for all causes of death and for all cancer was not high based on comparisons with national, state, and local rates.","Some effects of cigarette smoking, arsenic, and SO2 on mortality among US copper smelter workersAbs: Previous studies of the relationship between arsenic levels and respiratory cancer among copper smelter workers have not directly accounted for possible effects of SO2 exposure and cigarette smoking. This is a report on the 1949-1980 mortality experience of 6,078 white male workers who worked at least 3 years between 1 January 1946 and 31 December 1976 at one or more of eight US copper smelters. The completeness of the cohort was verified statistically, and worker exposures to arsenic, SO2, dust, nickel, cadmium, and lead were estimated from retrospective industrial hygiene surveys reported elsewhere. By using internal controls, a dose-response relationship for lung cancer was observed with exposure to arsenic and SO2. When cigarette smoking data were included with arsenic and SO2 exposure data in a nested case-control analysis, only smoking and arsenic were statistically significant factors. The arsenic-lung cancer relationship was confined to a single smelter associated with high content feed. In the remaining smelters mortality for all causes of death and for all cancer was not high based on comparisons with national, state, and local rates."
172,Morales et al. 2006,Bayesian model averaging with applications to benchmark dose estimation for arsenic in drinking water," An important component of quantitative risk assessment involves characterizing the dose-response relationship between an environmental exposure and adverse health outcome and then computing a benchmark dose, or the exposure level that yields a suitably low risk. This task is often complicated by model choice considerations, because risk estimates depend on the model parameters. We propose using Bayesian methods to address the problem of model selection and derive a model-averaged version of the benchmark dose. We illustrate the methods through application to data on arsenic-induced lung cancer from Taiwan.","Bayesian model averaging with applications to benchmark dose estimation for arsenic in drinking waterAbs: An important component of quantitative risk assessment involves characterizing the dose-response relationship between an environmental exposure and adverse health outcome and then computing a benchmark dose, or the exposure level that yields a suitably low risk. This task is often complicated by model choice considerations, because risk estimates depend on the model parameters. We propose using Bayesian methods to address the problem of model selection and derive a model-averaged version of the benchmark dose. We illustrate the methods through application to data on arsenic-induced lung cancer from Taiwan."
173,Hinwood et al. 2003,Hair and toenail arsenic concentrations of residents living in areas with high environmental arsenic concentrations," Surface soil and groundwater in Australia have been found to contain high concentrations of arsenic. The relative importance of long-term human exposure to these sources has not been established. Several studies have investigated long-term exposure to environmental arsenic concentrations using hair and toenails as the measure of exposure. Few have compared the difference in these measures of environmental sources of exposure. In this study we aimed to investigate risk factors for elevated hair and toenail arsenic concentrations in populations exposed to a range of environmental arsenic concentrations in both drinking water and soil as well as in a control population with low arsenic concentrations in both drinking water and soil. In this study, we recruited 153 participants from areas with elevated arsenic concentrations in drinking water and residential soil, as well as a control population with no anticipated arsenic exposures. The median drinking water arsenic concentrations in the exposed population were 43.8 Ág/L (range, 16.0-73 Ág/L) and median soil arsenic concentrations were 92.0 mg/kg (range, 9.1-9,900 mg/kg). In the control group, the median drinking water arsenic concentration was below the limit of detection, and the median soil arsenic concentration was 3.3 mg/kg. Participants were categorized based on household drinking water and residential soil arsenic concentrations. The geometric mean hair arsenic concentrations were 5.52 mg/kg for the drinking water exposure group and 3.31 mg/kg for the soil exposure group. The geometric mean toenail arsenic concentrations were 21.7 mg/kg for the drinking water exposure group and 32.1 mg/kg for the high-soil exposure group. Toenail arsenic concentrations were more strongly correlated with both drinking water and soil arsenic concentrations; however, there is a strong likelihood of significant external contamination. Measures of residential exposure were better predictors of hair and toenail arsenic concentrations than were local environmental concentrations.","Hair and toenail arsenic concentrations of residents living in areas with high environmental arsenic concentrationsAbs: Surface soil and groundwater in Australia have been found to contain high concentrations of arsenic. The relative importance of long-term human exposure to these sources has not been established. Several studies have investigated long-term exposure to environmental arsenic concentrations using hair and toenails as the measure of exposure. Few have compared the difference in these measures of environmental sources of exposure. In this study we aimed to investigate risk factors for elevated hair and toenail arsenic concentrations in populations exposed to a range of environmental arsenic concentrations in both drinking water and soil as well as in a control population with low arsenic concentrations in both drinking water and soil. In this study, we recruited 153 participants from areas with elevated arsenic concentrations in drinking water and residential soil, as well as a control population with no anticipated arsenic exposures. The median drinking water arsenic concentrations in the exposed population were 43.8 Ág/L (range, 16.0-73 Ág/L) and median soil arsenic concentrations were 92.0 mg/kg (range, 9.1-9,900 mg/kg). In the control group, the median drinking water arsenic concentration was below the limit of detection, and the median soil arsenic concentration was 3.3 mg/kg. Participants were categorized based on household drinking water and residential soil arsenic concentrations. The geometric mean hair arsenic concentrations were 5.52 mg/kg for the drinking water exposure group and 3.31 mg/kg for the soil exposure group. The geometric mean toenail arsenic concentrations were 21.7 mg/kg for the drinking water exposure group and 32.1 mg/kg for the high-soil exposure group. Toenail arsenic concentrations were more strongly correlated with both drinking water and soil arsenic concentrations; however, there is a strong likelihood of significant external contamination. Measures of residential exposure were better predictors of hair and toenail arsenic concentrations than were local environmental concentrations."
174,Viren and Silvers 1994,Unit risk estimates for airborne arsenic exposure: an updated view based on recent data from two copper smelter cohorts," The current unit risk for airborne arsenic, 4.29 x 10(-3), was established by the EPA in 1984. Using updated results from a cohort mortality study on Tacoma smelter workers and recent findings from a cohort study of 3619 Swedish smelter workers, new unit risk estimates were developed for the respective cohorts. Methods were analogous to those used by the EPA in 1984, and all estimates were derived under an absolute risk model. A new unit risk 1.28 x 10(-3), was estimated for the Tacoma smelter cohort which was a factor of 5 less than the EPA's earlier estimate, and a direct result of radically revised exposure estimates. A unit risk of 0.89 x 10(-3) was estimated from the Swedish study. Pooling these new unit risk estimates with the EPA's earlier estimates from the Montana smelter cohort yielded a composite unit risk of 1.43 x 10(-3). Based on this estimate, the present unit risk may overestimate the effects of airborne arsenic by a factor of 3. A need to update the unit risk for airborne arsenic and the collateral IRIS database is evident from the results.","Unit risk estimates for airborne arsenic exposure: an updated view based on recent data from two copper smelter cohortsAbs: The current unit risk for airborne arsenic, 4.29 x 10(-3), was established by the EPA in 1984. Using updated results from a cohort mortality study on Tacoma smelter workers and recent findings from a cohort study of 3619 Swedish smelter workers, new unit risk estimates were developed for the respective cohorts. Methods were analogous to those used by the EPA in 1984, and all estimates were derived under an absolute risk model. A new unit risk 1.28 x 10(-3), was estimated for the Tacoma smelter cohort which was a factor of 5 less than the EPA's earlier estimate, and a direct result of radically revised exposure estimates. A unit risk of 0.89 x 10(-3) was estimated from the Swedish study. Pooling these new unit risk estimates with the EPA's earlier estimates from the Montana smelter cohort yielded a composite unit risk of 1.43 x 10(-3). Based on this estimate, the present unit risk may overestimate the effects of airborne arsenic by a factor of 3. A need to update the unit risk for airborne arsenic and the collateral IRIS database is evident from the results."
175,Armstrong et al. 1984,Outbreak of fatal arsenic poisoning caused by contaminated drinking water," An outbreak of subacute poisoning occurred among nine members of a family; eight were ill with gastrointestinal symptoms, four developed encephalopathy, and two died. Abnormal liver function tests and leukopenia were common laboratory findings. Epidemiologic and environmental investigations traced the source of arsenic exposure to a farm well with water containing 108 ppm arsenic. The soil adjacent to the well was also contaminated with arsenic, possibly from waste pesticide. Presumably, arsenic gained access to the well through obvious leaks in the well's casing. To our knowledge, this is only the second reported outbreak of fatal arsenic poisoning from contaminated drinking water and one of few instances where illness followed exposure to a toxic substance which was disposed of, or possibly disposed of, in an indiscriminate manner.","Outbreak of fatal arsenic poisoning caused by contaminated drinking waterAbs: An outbreak of subacute poisoning occurred among nine members of a family; eight were ill with gastrointestinal symptoms, four developed encephalopathy, and two died. Abnormal liver function tests and leukopenia were common laboratory findings. Epidemiologic and environmental investigations traced the source of arsenic exposure to a farm well with water containing 108 ppm arsenic. The soil adjacent to the well was also contaminated with arsenic, possibly from waste pesticide. Presumably, arsenic gained access to the well through obvious leaks in the well's casing. To our knowledge, this is only the second reported outbreak of fatal arsenic poisoning from contaminated drinking water and one of few instances where illness followed exposure to a toxic substance which was disposed of, or possibly disposed of, in an indiscriminate manner."
176,Kyle and Pease 1965,Hematologic aspects of arsenic intoxication," Six cases are presented involving arsenic (7440382) intoxication proved by examination of urine, hair, and nails. Nausea, vomiting, fatigue, diarrhea, pigmentation, keratosis and peripheral neuropathy are prominent clinical features. Anemia and leukopenia are found in all patients and thrombocytopenia in three, basophilic stippling being a prominent finding. Bone marrow examination of 4 patients shows increased, disturbed erythropoiesis in 3 and depressed or disturbed myelopoiesis in 4. The hematologic abnormalities disappear within two or three weeks after cessation of arsenic ingestion. Arsenic intoxication should be considered for diagnosis when gastrointestinal symptoms or pancytopenia is present.","Hematologic aspects of arsenic intoxicationAbs: Six cases are presented involving arsenic (7440382) intoxication proved by examination of urine, hair, and nails. Nausea, vomiting, fatigue, diarrhea, pigmentation, keratosis and peripheral neuropathy are prominent clinical features. Anemia and leukopenia are found in all patients and thrombocytopenia in three, basophilic stippling being a prominent finding. Bone marrow examination of 4 patients shows increased, disturbed erythropoiesis in 3 and depressed or disturbed myelopoiesis in 4. The hematologic abnormalities disappear within two or three weeks after cessation of arsenic ingestion. Arsenic intoxication should be considered for diagnosis when gastrointestinal symptoms or pancytopenia is present."
177,Woods & Fowler & 1977,Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liver," In these studies the effects of ingested arsenic (As(+5)) on hepatic heme biosynthetic capability and hemoprotein function in adult male rats were investigated. Animals exposed for 6 weeks to 0, 20, 40, or 85 ppm sodium arsenate in the drinking water suffered depression of hepatic delta-aminolevulinic acid (ALA) synthetase and heme synthetase (ferrochelatase) activities, with maximal decreases to 67 and 55% of control levels, respectively, at 85 ppm. Concomitantly, urinary uroporphyrin levels were elevated by as much as 12 times, and coproporphyrin by as much as 9 times, control values. The rate of incorporation of (3)H-ALA into mitochondrial and microsomal hemes was depressed by 40-50% at 20 ppm but was increased with regard to controls by as much as 150% at the higher treatment levels. A similar biphasic pattern was observed in regard to (14)C-leucine incorporation into cellular membranal proteins. In contrast, the levels of ALA dehydratase, uroporphyrinogen I synthetase, aminopyrine demethylase, and cytochrome P-450 were not significantly changed in As(+5)-treated rats. These results support the hypothesis that chronic, low level, arsenic exposure results in selective inhibition of mitochondrial-bound heme biosynthetic pathway enzymes (ALA synthetase and heme synthetase) resulting in a substantial increase in urinary porphyrins, uniquely characterized by a greater increase in uroporphyrin than coproporphyrin levels. These changes occur independent of, or prior to, alterations in hepatic hemoprotein-dependent functions and may thus serve in the clinical analysis of pretoxic exposure to arsenic compounds in human populations.","Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liverAbs: In these studies the effects of ingested arsenic (As(+5)) on hepatic heme biosynthetic capability and hemoprotein function in adult male rats were investigated. Animals exposed for 6 weeks to 0, 20, 40, or 85 ppm sodium arsenate in the drinking water suffered depression of hepatic delta-aminolevulinic acid (ALA) synthetase and heme synthetase (ferrochelatase) activities, with maximal decreases to 67 and 55% of control levels, respectively, at 85 ppm. Concomitantly, urinary uroporphyrin levels were elevated by as much as 12 times, and coproporphyrin by as much as 9 times, control values. The rate of incorporation of (3)H-ALA into mitochondrial and microsomal hemes was depressed by 40-50% at 20 ppm but was increased with regard to controls by as much as 150% at the higher treatment levels. A similar biphasic pattern was observed in regard to (14)C-leucine incorporation into cellular membranal proteins. In contrast, the levels of ALA dehydratase, uroporphyrinogen I synthetase, aminopyrine demethylase, and cytochrome P-450 were not significantly changed in As(+5)-treated rats. These results support the hypothesis that chronic, low level, arsenic exposure results in selective inhibition of mitochondrial-bound heme biosynthetic pathway enzymes (ALA synthetase and heme synthetase) resulting in a substantial increase in urinary porphyrins, uniquely characterized by a greater increase in uroporphyrin than coproporphyrin levels. These changes occur independent of, or prior to, alterations in hepatic hemoprotein-dependent functions and may thus serve in the clinical analysis of pretoxic exposure to arsenic compounds in human populations."
178,Lee-Feldstein 1989,A comparison of several measures of exposure to arsenic: matched case-control study of copper smelter employees," To explore the relation between respiratory cancer mortality and exposure to airborne arsenic, methods of conditional logistic regression analysis are applied to a matched case-control study of copper smelter employees in Montana. With follow-up data for the period 1938-1977, several measures of arsenic exposure are compared. For men first employed prior to 1925, three measures--the category of maximum arsenic exposure, cumulative arsenic exposure, and time-weighted average arsenic exposure--are good predictors of respiratory cancer mortality. Within this group, there was a significantly elevated relative risk of respiratory cancer mortality associated with medium and heavy exposure to arsenic. For men first employed during 1925-1947, time-weighted average exposure to arsenic (adjusted for age at first employment) is the best predictor. In this group, men with heavy arsenic exposure and initially employed at 16.9 years had a relative risk of 6.0 in comparison to the baseline group with only light exposure to arsenic and initially employed at 31.9 years. No particular advantage is found in lagging exposures 10 years prior to death of the case in each matched set.","A comparison of several measures of exposure to arsenic: matched case-control study of copper smelter employeesAbs: To explore the relation between respiratory cancer mortality and exposure to airborne arsenic, methods of conditional logistic regression analysis are applied to a matched case-control study of copper smelter employees in Montana. With follow-up data for the period 1938-1977, several measures of arsenic exposure are compared. For men first employed prior to 1925, three measures--the category of maximum arsenic exposure, cumulative arsenic exposure, and time-weighted average arsenic exposure--are good predictors of respiratory cancer mortality. Within this group, there was a significantly elevated relative risk of respiratory cancer mortality associated with medium and heavy exposure to arsenic. For men first employed during 1925-1947, time-weighted average exposure to arsenic (adjusted for age at first employment) is the best predictor. In this group, men with heavy arsenic exposure and initially employed at 16.9 years had a relative risk of 6.0 in comparison to the baseline group with only light exposure to arsenic and initially employed at 31.9 years. No particular advantage is found in lagging exposures 10 years prior to death of the case in each matched set."
179,Pineda-Zavaleta et al. 2004,"Nitric oxide and superoxide anion production in monocytes from children exposed to arsenic and lead in region Lagunera, Mexico"," We evaluated in Mexican children environmentally exposed to arsenic and lead monocyte nitric oxide (NO) and superoxide anion production in response to direct activation with interferon-""gamma"" (IFN-""gamma"") + lipopolysaccharide (LPS). The integrity of Th1-regulated cellular immune response when monocytes were indirectly activated was also evaluated. Most children lived near a primary lead smelter. Lead and arsenic contamination in soil and dust by far exceeded background levels. As levels in water were between 10 and 30 ppb. Most children (93%) had urinary arsenic (AsU) concentrations above 50 Ág/l (range 16.75-465.75) and 65% had lead blood levels (PbB) above 10 Ág/dl (range 3.47-49.19). Multivariate analyses showed that NO production in monocytes activated indirectly was negatively associated with both PbB and AsU. Superoxide production in directly activated monocytes was negatively associated with AsU but positively associated with PbB. The models including the interaction term for AsU and PbB suggested the possibility of a negative interaction for NO production and a positive interaction for superoxide. There were indications of differential gender-based associations, NO production in indirectly activated monocytes obtained from girls was negatively associated with AsU but not with PbB. Superoxide production was positively associated with PbB in both directly and indirectly activated monocytes from boys but the latter was negatively associated with AsU. These effects are consistent with immune system abnormalities observed in human populations exposed to Pb or As. Further studies in larger populations are required to characterize As and Pb interactions and the mechanism(s) underlying the observed effects.","Nitric oxide and superoxide anion production in monocytes from children exposed to arsenic and lead in region Lagunera, MexicoAbs: We evaluated in Mexican children environmentally exposed to arsenic and lead monocyte nitric oxide (NO) and superoxide anion production in response to direct activation with interferon-""gamma"" (IFN-""gamma"") + lipopolysaccharide (LPS). The integrity of Th1-regulated cellular immune response when monocytes were indirectly activated was also evaluated. Most children lived near a primary lead smelter. Lead and arsenic contamination in soil and dust by far exceeded background levels. As levels in water were between 10 and 30 ppb. Most children (93%) had urinary arsenic (AsU) concentrations above 50 Ág/l (range 16.75-465.75) and 65% had lead blood levels (PbB) above 10 Ág/dl (range 3.47-49.19). Multivariate analyses showed that NO production in monocytes activated indirectly was negatively associated with both PbB and AsU. Superoxide production in directly activated monocytes was negatively associated with AsU but positively associated with PbB. The models including the interaction term for AsU and PbB suggested the possibility of a negative interaction for NO production and a positive interaction for superoxide. There were indications of differential gender-based associations, NO production in indirectly activated monocytes obtained from girls was negatively associated with AsU but not with PbB. Superoxide production was positively associated with PbB in both directly and indirectly activated monocytes from boys but the latter was negatively associated with AsU. These effects are consistent with immune system abnormalities observed in human populations exposed to Pb or As. Further studies in larger populations are required to characterize As and Pb interactions and the mechanism(s) underlying the observed effects."
180,Sengupta and Bishayi 2002,Effect of lead and arsenic on murine macrophage response," #Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages. Results show that there is a significant decrease in alkaline phosphatase release in lead treated macrophages (6.7 +/- 0.88 IU/100 mL) with respect to control (14.17 +/- 0.18). In vivo exposure of sodium arsenite (0.5 mg/kg body wt) also decreases phagocytic activity for ingestion and digestion of exogenous antigens, such as whole microorganism, as evident from the phagocytic index, 11555.55 +/- 62.86 (in control) to 5555.5 +/- 1571.33 in arsenic treated cells. Arsenic exposed cells release 8.15 +/- 0.05 microM nitric oxide, whereas control cells release 10.95 +/- 0.15 microM of nitric oxide, which is also identical following LPS stimulation. Results show that the functional integrity of the target cell is also decreased after arsenic exposure as obtained from the percentage of DNA fragmentation. A greater percentage of DNA fragmentation upon arsenic treatment (43.1 +/- 0.05%) with respect to control (14.9 +/- 0.34%) indicates that arsenic induces apoptosis. In immune cells which are rapidly proliferating and differentiating, inhibition of these heavy metal induced functions may result in similar degree of toxicity and lead to diseased state.","Effect of lead and arsenic on murine macrophage responseAbs: #Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages. Results show that there is a significant decrease in alkaline phosphatase release in lead treated macrophages (6.7 +/- 0.88 IU/100 mL) with respect to control (14.17 +/- 0.18). In vivo exposure of sodium arsenite (0.5 mg/kg body wt) also decreases phagocytic activity for ingestion and digestion of exogenous antigens, such as whole microorganism, as evident from the phagocytic index, 11555.55 +/- 62.86 (in control) to 5555.5 +/- 1571.33 in arsenic treated cells. Arsenic exposed cells release 8.15 +/- 0.05 microM nitric oxide, whereas control cells release 10.95 +/- 0.15 microM of nitric oxide, which is also identical following LPS stimulation. Results show that the functional integrity of the target cell is also decreased after arsenic exposure as obtained from the percentage of DNA fragmentation. A greater percentage of DNA fragmentation upon arsenic treatment (43.1 +/- 0.05%) with respect to control (14.9 +/- 0.34%) indicates that arsenic induces apoptosis. In immune cells which are rapidly proliferating and differentiating, inhibition of these heavy metal induced functions may result in similar degree of toxicity and lead to diseased state."
181,Handson 1984,Lead and arsenic levels in wines produced from vineyards where lead arsenate sprays are used for caterpillar control, Twenty-seven dry table wines from 14 wineries throughout Victoria were analysed for lead and arsenic. Wines originating from vineyards using lead arsenate insecticide for caterpillar control had mean levels of 0.31 mg litre--1 lead and 0.08 mg litre--1 arsenic. The mean levels in similar wines from wineries not using lead arsenate sprays were 0.03 mg litre--1 and less than 0.01 mg litre--1 respectively.,Lead and arsenic levels in wines produced from vineyards where lead arsenate sprays are used for caterpillar controlAbs: Twenty-seven dry table wines from 14 wineries throughout Victoria were analysed for lead and arsenic. Wines originating from vineyards using lead arsenate insecticide for caterpillar control had mean levels of 0.31 mg litre--1 lead and 0.08 mg litre--1 arsenic. The mean levels in similar wines from wineries not using lead arsenate sprays were 0.03 mg litre--1 and less than 0.01 mg litre--1 respectively.
182,Sams et al. 2007,Workshop overview: Arsenic research and risk assessment," The chronic exposure of humans through consumption of high levels of inorganic arsenic (iAs)-contaminated drinking water is associated with skin lesions, peripheral vascular disease, hypertension, and cancers. Additionally, humans are exposed to organic arsenicals when used as pesticides and herbicides (e.g., monomethylarsonic acid, dimethylarsinic acid (DMAV) also known as cacodylic acid). Extensive research has been conducted to characterize the adverse health effects that result from exposure to iAs and its metabolites to describe the biological pathway(s) that lead to adverse health effects. To further this effort, on May 31, 2006, the United States Environmental Protection Agency (USEPA) sponsored a meeting entitled “Workshop on Arsenic Research and Risk Assessment”. The invited participants from government agencies, academia, independent research organizations and consultants were asked to present their current research. The overall focus of these research efforts has been to determine the potential human health risks due to environmental exposures to arsenicals. Pursuant in these efforts is the elucidation of a mode of action for arsenicals. This paper provides a brief overview of the workshop goals, regulatory context for arsenical research, mode of action (MOA) analysis in human health risk assessment, and the application of MOA analysis for iAs and DMAV. Subsequent papers within this issue will present the research discussed at the workshop, ensuing discussions, and conclusions of the workshop.","Workshop overview: Arsenic research and risk assessmentAbs: The chronic exposure of humans through consumption of high levels of inorganic arsenic (iAs)-contaminated drinking water is associated with skin lesions, peripheral vascular disease, hypertension, and cancers. Additionally, humans are exposed to organic arsenicals when used as pesticides and herbicides (e.g., monomethylarsonic acid, dimethylarsinic acid (DMAV) also known as cacodylic acid). Extensive research has been conducted to characterize the adverse health effects that result from exposure to iAs and its metabolites to describe the biological pathway(s) that lead to adverse health effects. To further this effort, on May 31, 2006, the United States Environmental Protection Agency (USEPA) sponsored a meeting entitled “Workshop on Arsenic Research and Risk Assessment”. The invited participants from government agencies, academia, independent research organizations and consultants were asked to present their current research. The overall focus of these research efforts has been to determine the potential human health risks due to environmental exposures to arsenicals. Pursuant in these efforts is the elucidation of a mode of action for arsenicals. This paper provides a brief overview of the workshop goals, regulatory context for arsenical research, mode of action (MOA) analysis in human health risk assessment, and the application of MOA analysis for iAs and DMAV. Subsequent papers within this issue will present the research discussed at the workshop, ensuing discussions, and conclusions of the workshop."
183,Paul et al. 2007,Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes," Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues.","Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetesAbs: Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues."
184,Ning et al. 2007,"Residential exposure to drinking water arsenic in Inner Mongolia, China"," In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 ?g of As/L); Spot method (detection limit, 10 ?g of As/L); and air assisted Colorimetry method (detection limit, 20 ?g of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 ?g of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980–1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 ?g of As/L (14,500 above 50 ?g of As/L—the current China national standard in drinking water and 2198 above 300 ?g of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.","Residential exposure to drinking water arsenic in Inner Mongolia, ChinaAbs: In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 ?g of As/L); Spot method (detection limit, 10 ?g of As/L); and air assisted Colorimetry method (detection limit, 20 ?g of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 ?g of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980–1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 ?g of As/L (14,500 above 50 ?g of As/L—the current China national standard in drinking water and 2198 above 300 ?g of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region."
185,Li et al. 2005,Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype," Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If iAs methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago.","Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotypeAbs: Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If iAs methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago."
186,Kwok et al. 2007,"Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, China"," The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 ?g of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and > 100 ?g of As/L, respectively. Controlling for age and body weight (n = 3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n = 3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and > 100 ?g of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.","Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, ChinaAbs: The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 ?g of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and > 100 ?g of As/L, respectively. Controlling for age and body weight (n = 3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n = 3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and > 100 ?g of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant."
187,Ihrig et al. 1998,A hospital-based case-control study of stillbirths and environmental exposure to arsenic using an atmospheric dispersion model linked to a geographical information system," Although adverse reproductive outcomes have been associated with arsenic exposure, the extent and severity of the effects of chronic inhalation of low levels of arsenic on reproduction are not known. We conducted a hospital-based case-control study of stillbirths in a central Texas community that included a facility with more than a 60-year history of producing primarily arsenic-based agricultural products. We collected data on 119 cases and 267 controls randomly selected from healthy live-births at the same hospital and matched for year of birth. We abstracted medical and demographic data for the period January 1, 1983, to December 31, 1993, from hospital records and estimated socioeconomic status by median income from the 1990 Population and Housing Census data. We estimated arsenic exposure levels from airborne emission estimates and an atmospheric dispersion model and linked the results to a geographical information system (GIS) database. Exposure was linked by GIS to residential address at time of delivery. A conditional logistic regression model was fitted including maternal age, race/ethnicity, parity, income group, exposure as a categorical variable, and exposure-race/ethnicity interaction. The prevalence odds ratio observed for Hispanics in the high-exposure group (>100 ng per m3 arsenic) was 8.4, with a 95% confidence interval of 1.4-50.1.","A hospital-based case-control study of stillbirths and environmental exposure to arsenic using an atmospheric dispersion model linked to a geographical information systemAbs: Although adverse reproductive outcomes have been associated with arsenic exposure, the extent and severity of the effects of chronic inhalation of low levels of arsenic on reproduction are not known. We conducted a hospital-based case-control study of stillbirths in a central Texas community that included a facility with more than a 60-year history of producing primarily arsenic-based agricultural products. We collected data on 119 cases and 267 controls randomly selected from healthy live-births at the same hospital and matched for year of birth. We abstracted medical and demographic data for the period January 1, 1983, to December 31, 1993, from hospital records and estimated socioeconomic status by median income from the 1990 Population and Housing Census data. We estimated arsenic exposure levels from airborne emission estimates and an atmospheric dispersion model and linked the results to a geographical information system (GIS) database. Exposure was linked by GIS to residential address at time of delivery. A conditional logistic regression model was fitted including maternal age, race/ethnicity, parity, income group, exposure as a categorical variable, and exposure-race/ethnicity interaction. The prevalence odds ratio observed for Hispanics in the high-exposure group (>100 ng per m3 arsenic) was 8.4, with a 95% confidence interval of 1.4-50.1."
188,Devesa et al. 2006,Arsenicals in maternal and fetal mouse tissues after gestational exposure to arsenite," Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of these exposure regimens. Tissues were collected from three females and from associated fetuses exposed to each dosage level. Concentrations of total speciated arsenic (sum of inorganic, methyl, and dimethyl arsenic) were higher in maternal tissues than in placenta and fetal tissues; total speciated arsenic concentration in placenta exceeded those in fetal tissues. Significant dosage-dependent (42.5 ppm versus 85 ppm of arsenite in drinking water) differences were found in total speciated arsenic concentrations in maternal lung (p < 0.01) and liver (p < 0.001). Total speciated arsenic concentrations did not differ significantly between dosage levels for maternal blood or for fetal lung, liver, and blood, or for placenta. Percentages of inorganic, methyl, or dimethyl arsenic in maternal or fetal tissues were not dosage-dependent. Over the range of total speciated arsenic concentrations in most maternal and fetal tissues, dimethyl arsenic was the most abundant arsenical. However, in maternal liver at the highest total speciated arsenic concentration, inorganic arsenic was the most abundant arsenical, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ. Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus.","Arsenicals in maternal and fetal mouse tissues after gestational exposure to arseniteAbs: Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of these exposure regimens. Tissues were collected from three females and from associated fetuses exposed to each dosage level. Concentrations of total speciated arsenic (sum of inorganic, methyl, and dimethyl arsenic) were higher in maternal tissues than in placenta and fetal tissues; total speciated arsenic concentration in placenta exceeded those in fetal tissues. Significant dosage-dependent (42.5 ppm versus 85 ppm of arsenite in drinking water) differences were found in total speciated arsenic concentrations in maternal lung (p < 0.01) and liver (p < 0.001). Total speciated arsenic concentrations did not differ significantly between dosage levels for maternal blood or for fetal lung, liver, and blood, or for placenta. Percentages of inorganic, methyl, or dimethyl arsenic in maternal or fetal tissues were not dosage-dependent. Over the range of total speciated arsenic concentrations in most maternal and fetal tissues, dimethyl arsenic was the most abundant arsenical. However, in maternal liver at the highest total speciated arsenic concentration, inorganic arsenic was the most abundant arsenical, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ. Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus."
189,Clewell and Crump 2005,Quantitative estimates of risk for noncancer endpoints,"While quantitative estimates of risk have been a standard practice in cancer risk assessment for many years, no similar practice is evident in noncancer risk assessment. We use two recent examples involving methylmercury and arsenic to illustrate the negative impact of this discrepancy on risk communication and cost-benefit analysis. We argue for a more balanced treatment of cancer and noncancer risks and suggest an approach for reaching this goal.","Quantitative estimates of risk for noncancer endpointsAbs:While quantitative estimates of risk have been a standard practice in cancer risk assessment for many years, no similar practice is evident in noncancer risk assessment. We use two recent examples involving methylmercury and arsenic to illustrate the negative impact of this discrepancy on risk communication and cost-benefit analysis. We argue for a more balanced treatment of cancer and noncancer risks and suggest an approach for reaching this goal."
190,Sax et al. 2006,A cancer risk assessment of inner-city teenagers living in New York City and Los Angeles,"BACKGROUND: The Taxies Exposure Assessment Columbia-Harvard (TEACH) project assessed exposures and cancer risks from urban air pollutants in a population of high school teenagers in New York City (NYC) and Los Angeles (LA). Forty-six high school students participated in NYC and 41 in LA, most in two seasons in 1999 and 2000, respectively. METHODS: Personal, indoor home, and outdoor home 48-hr samples of volatile organic compounds (VOCS), aldehydes, particulate matter with aerodynamic diameter <= 2.5 mu m, and particle-bound elements were collected. Individual cancer risks for 13 VOCs and 6 particle-bound elements were calculated from personal concentrations and published cancer unit risks. RESULTS: The median cumulative risk from personal VOC exposures for this sample of NYC high school students was 666 per million and was greater than the risks from ambient exposures by a factor of about 5. In the LA sample, median cancer risks from VOC personal exposures were 486 per million, about a factor of 4 greater than ambient exposure risks. The VOCs with the highest cancer risk included 1,4-dichlorobenzene, formaldehyde, chloroform, acetaldehyde, and benzene. Of these, benzene had the greatest contributions from outdoor sources. All others had high contributions from indoor sources. The cumulative risks from personal exposures to the elements were an order of magnitude lower than cancer risks from VOC exposures. CONCLUSIONS: Most VOCs had median upper-bound lifetime cancer risks that exceeded the U.S. Environmental Protection Agency (EPA) benchmark of 1 x 10(-6) and were generally greater than U.S. EPA modeled estimates, more so for compounds with predominant indoor sources. Chromium, nickel, and arsenic had median personal cancer risks above the U.S. EPA benchmark with exposures largely from outdoors and other microenvironments. The U.S. EPA-modeled concentrations tended to overestimate personal cancer risks for beryllium and chromium but underestimate risks for nickel and arsenic.","A cancer risk assessment of inner-city teenagers living in New York City and Los AngelesAbs:BACKGROUND: The Taxies Exposure Assessment Columbia-Harvard (TEACH) project assessed exposures and cancer risks from urban air pollutants in a population of high school teenagers in New York City (NYC) and Los Angeles (LA). Forty-six high school students participated in NYC and 41 in LA, most in two seasons in 1999 and 2000, respectively. METHODS: Personal, indoor home, and outdoor home 48-hr samples of volatile organic compounds (VOCS), aldehydes, particulate matter with aerodynamic diameter <= 2.5 mu m, and particle-bound elements were collected. Individual cancer risks for 13 VOCs and 6 particle-bound elements were calculated from personal concentrations and published cancer unit risks. RESULTS: The median cumulative risk from personal VOC exposures for this sample of NYC high school students was 666 per million and was greater than the risks from ambient exposures by a factor of about 5. In the LA sample, median cancer risks from VOC personal exposures were 486 per million, about a factor of 4 greater than ambient exposure risks. The VOCs with the highest cancer risk included 1,4-dichlorobenzene, formaldehyde, chloroform, acetaldehyde, and benzene. Of these, benzene had the greatest contributions from outdoor sources. All others had high contributions from indoor sources. The cumulative risks from personal exposures to the elements were an order of magnitude lower than cancer risks from VOC exposures. CONCLUSIONS: Most VOCs had median upper-bound lifetime cancer risks that exceeded the U.S. Environmental Protection Agency (EPA) benchmark of 1 x 10(-6) and were generally greater than U.S. EPA modeled estimates, more so for compounds with predominant indoor sources. Chromium, nickel, and arsenic had median personal cancer risks above the U.S. EPA benchmark with exposures largely from outdoors and other microenvironments. The U.S. EPA-modeled concentrations tended to overestimate personal cancer risks for beryllium and chromium but underestimate risks for nickel and arsenic."
191,Costa et al. 2008,Modelling metallothioneinnductionn the liverf Sparus aurata exposed to metal-contaminated sediments," Metallothionein (MT)n the liverf gilthead seabreams (Sparus aurata L., 1758) exposed to Sado estuary (Portugal) sediments was quantified to assess the MTnduction potential as a biomarkerf sediment-based contamination by copper (Cu), cadmium (Cd), lead (Pb) and arsenic (As). Sediments were collected from two control sites and four sites withifferent levelsf contamination. Sediment Cu, Cd, Pb, As, totalrganic matter (TOM) and fine fraction (FF) levels wereetermined. Generalized linear models (GLM) allowedntegrationf sediment parameters with liver Cu, Cd, Pb, As and MT concentrations. Although sediment metal levels were lower than expected, we relate MT with liver Cd and also withnteractions between liver and sediment Cu and between liver Cu and TOM. We suggestntegrating biomarkers and environmental parameters using statistical models such as GLM as a more sensitive and reliable technique for sediment risk assessment than traditionalsolated biomarker approaches.","Modelling metallothioneinnductionn the liverf Sparus aurata exposed to metal-contaminated sedimentsAbs: Metallothionein (MT)n the liverf gilthead seabreams (Sparus aurata L., 1758) exposed to Sado estuary (Portugal) sediments was quantified to assess the MTnduction potential as a biomarkerf sediment-based contamination by copper (Cu), cadmium (Cd), lead (Pb) and arsenic (As). Sediments were collected from two control sites and four sites withifferent levelsf contamination. Sediment Cu, Cd, Pb, As, totalrganic matter (TOM) and fine fraction (FF) levels wereetermined. Generalized linear models (GLM) allowedntegrationf sediment parameters with liver Cu, Cd, Pb, As and MT concentrations. Although sediment metal levels were lower than expected, we relate MT with liver Cd and also withnteractions between liver and sediment Cu and between liver Cu and TOM. We suggestntegrating biomarkers and environmental parameters using statistical models such as GLM as a more sensitive and reliable technique for sediment risk assessment than traditionalsolated biomarker approaches."
192,Ed et al. 2007,Risk-based evaluation of the exposure of children to trace elements in playgrounds in Madrid (Spain)," Eighty samples of sandy substrate were collected in November 2002 and 2003, from 20 municipal playgrounds in Madrid (Spain) to assess the potential adverse health effects of the exposure of children to trace elements in this material during their games. In each playground, two 500 g samples were collected, dried at 45 degrees C for 48 h, sieved below 100 microm, acid digested and analyzed by ICP-MS. Doses contacted through ingestion and inhalation and the dose absorbed through the skin were calculated using USEPAs hourly exposure parameters for children and the results of an in situ survey. The toxicity values considered in this study were mostly taken from the US DoEs RAIS compilation. The results of the risk assessment indicate that the highest risk is associated with ingestion of soil particles and that the trace element of most concern is arsenic, the exposure to which results in a cancer risk value of 4.19 x 10(-6), close to the 1 x 10(-5) probability level deemed unacceptable by most regulatory agencies. Regarding non-cancer effects, exposure to playground substrate yields an aggregate Hazard Index of 0.28, below the threshold value of 1 (with As, again, as the largest single contributor, followed by Pb, Cr, Al and Mn). Although the uncertainties associated with the estimates of toxicity values and exposure factors should be reduced before any definite conclusions regarding potential health effects are drawn, risk assessment has proven to be a very useful tool to identify the contaminants and exposure pathways of most concern in urban environments.","Risk-based evaluation of the exposure of children to trace elements in playgrounds in Madrid (Spain)Abs: Eighty samples of sandy substrate were collected in November 2002 and 2003, from 20 municipal playgrounds in Madrid (Spain) to assess the potential adverse health effects of the exposure of children to trace elements in this material during their games. In each playground, two 500 g samples were collected, dried at 45 degrees C for 48 h, sieved below 100 microm, acid digested and analyzed by ICP-MS. Doses contacted through ingestion and inhalation and the dose absorbed through the skin were calculated using USEPAs hourly exposure parameters for children and the results of an in situ survey. The toxicity values considered in this study were mostly taken from the US DoEs RAIS compilation. The results of the risk assessment indicate that the highest risk is associated with ingestion of soil particles and that the trace element of most concern is arsenic, the exposure to which results in a cancer risk value of 4.19 x 10(-6), close to the 1 x 10(-5) probability level deemed unacceptable by most regulatory agencies. Regarding non-cancer effects, exposure to playground substrate yields an aggregate Hazard Index of 0.28, below the threshold value of 1 (with As, again, as the largest single contributor, followed by Pb, Cr, Al and Mn). Although the uncertainties associated with the estimates of toxicity values and exposure factors should be reduced before any definite conclusions regarding potential health effects are drawn, risk assessment has proven to be a very useful tool to identify the contaminants and exposure pathways of most concern in urban environments."
193,Rocha-Amador et al. 2007,DisminuciÃ³n de la inteligencia en niÃ±os y exposiciÃ³n al fl Ãºor y arsÃ©nico en el agua potable," Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.","DisminuciÃ³n de la inteligencia en niÃ±os y exposiciÃ³n al fl Ãºor y arsÃ©nico en el agua potableAbs: Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores."
194,Shinn et al. 2003,Atmospheric transport of mold spores in clouds of desert dust," Fungal spores can be transported globally in clouds of desert dust. Many species of fungi (commonly known as molds) and bacteria—including some that are human pathogens—have characteristics suited to long-range atmospheric transport. Dust from the African desert can affect air quality in Africa, Europe, the Middle East, and the Americas. Asian desert dust can affect air quality in Asia, the Arctic, North America, and Europe. Atmospheric exposure to mold-carrying desert dust may affect human health directly through allergic induction of respiratory stress. In addition, mold spores within these dust clouds may seed downwind ecosystems in both outdoor and indoor environments.","Atmospheric transport of mold spores in clouds of desert dustAbs: Fungal spores can be transported globally in clouds of desert dust. Many species of fungi (commonly known as molds) and bacteria—including some that are human pathogens—have characteristics suited to long-range atmospheric transport. Dust from the African desert can affect air quality in Africa, Europe, the Middle East, and the Americas. Asian desert dust can affect air quality in Asia, the Arctic, North America, and Europe. Atmospheric exposure to mold-carrying desert dust may affect human health directly through allergic induction of respiratory stress. In addition, mold spores within these dust clouds may seed downwind ecosystems in both outdoor and indoor environments."
195,Wasserman et al. 2004,"Water arsenic exposure and children's intellectual function in Araihazar, Bangladesh"," Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child’s home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose–response manner, such that children with water As levels > 50 ?g/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 ?g/L. The association was generally stronger for well-water As than for urinary As.","Water arsenic exposure and children's intellectual function in Araihazar, BangladeshAbs: Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child’s home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose–response manner, such that children with water As levels > 50 ?g/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 ?g/L. The association was generally stronger for well-water As than for urinary As."
196,Tsai et al. 2003,The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence," This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0±605824.2 and 13782.2±12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.","The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescenceAbs: This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0±605824.2 and 13782.2±12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion."
197,Williams et al. 1989,Infectious and noninfectious exposures in the etiology of light chain myeloma: a case-control study," Sixty-nine subjects with light chain myeloma were interviewed in a multicenter case-control study, and their responses were compared to those of 1683 controls selected from the general population of the same geographic areas. The interview was directed at the subject's history of exposure to a variety of chemical and infectious agents. Persons with a history of a medical implant had 2.2 times the risk of other persons (95% confidence interval = 0.9-5.8), a relative risk that increased with increasing time that the implant had been present. Alkali exposure that was deemed by the subject to be unusually heavy was associated with a relative risk of light chain myeloma of 7.8 (95% confidence interval = 1.7-35.3), while similarly defined exposure to carbon monoxide increased the risk by 6.1 times (95% confidence interval = 2.0-18.2). These findings differ from those obtained in our study of the more common forms of multiple myeloma and, while the differences are plausibly due only to chance given the large number of exposures investigated, they could be an indication that light chain myeloma is an etiologically distinct entity.","Infectious and noninfectious exposures in the etiology of light chain myeloma: a case-control studyAbs: Sixty-nine subjects with light chain myeloma were interviewed in a multicenter case-control study, and their responses were compared to those of 1683 controls selected from the general population of the same geographic areas. The interview was directed at the subject's history of exposure to a variety of chemical and infectious agents. Persons with a history of a medical implant had 2.2 times the risk of other persons (95% confidence interval = 0.9-5.8), a relative risk that increased with increasing time that the implant had been present. Alkali exposure that was deemed by the subject to be unusually heavy was associated with a relative risk of light chain myeloma of 7.8 (95% confidence interval = 1.7-35.3), while similarly defined exposure to carbon monoxide increased the risk by 6.1 times (95% confidence interval = 2.0-18.2). These findings differ from those obtained in our study of the more common forms of multiple myeloma and, while the differences are plausibly due only to chance given the large number of exposures investigated, they could be an indication that light chain myeloma is an etiologically distinct entity."
198,Franzblau et al. 1988,Use of inductively coupled plasma-atomic emission spectroscopy (ICP-AES) in screening for trace metal exposures in an industrial population," A study of trace metal concentrations in the hair and blood of an industrial population was conducted. The study group consisted of 84 male plumbers and pipe fitters, 23 to 72 years old. Blood and hair samples were collected and analyzed for lead (7439921), arsenic (7440382), chromium (7440473), zinc (7440666), selenium (7782492), cadmium (7440439), iron (7439896), nickel (7440020), copper (7440508), or aluminum (7429905) by inductively coupled plasma atomic emission spectroscopy. Samples were also analyzed for zinc-protoporphyrin to heme ratio (ZPP/heme) by hematofluorometry. Subjects completed a questionnaire detailing occupational histories and exposures to lead, arsenic, zinc, cadmium, nickel, chromium, copper, and aluminum. Eighty one percent of the cohort was White, 8.3 percent Black, 2.4 percent Asian, and 2.4 percent Native American. Sixty six subjects were actively employed. Mean blood metal concentrations were: lead, 0.41 micrograms per milliliter (microg/ml); arsenic, 0.65microg/ml; zinc, 7.92microg/ml; selenium, 0.13microg/ml; cadmium, 0.001microg/ml; iron, 528microg/ml; nickel, 0.04microg/ml; chromium, 0.55microg/ml; copper, 1.00microg/ml; and aluminum, 0.59microg/ml. Mean ZPP/heme ratio was 40.5. Mean hair metal concentrations were: lead, 32micrograms per gram (microg/g); arsenic, 1.5microg/g; zinc, 200microg/g; selenium, 2.5microg/g; cadmium, 1.7microg/g; iron, 29.1microg/g; nickel, 1.9microg/g; chromium, 3.1microg/g; copper, 49.3microg/g; and aluminum, 15.2microg/g. Only copper and chromium blood and hair concentrations were significantly positively correlated. No significant correlation between blood and hair concentrations was seen in the group reporting metal exposure versus those reporting no exposure. The authors note that the metal concentrations are comparable to those found previously in nonexposed groups. It is difficult to distinguish exposed asymptomatic workers from nonexposed workers without having detailed information on the workplace.","Use of inductively coupled plasma-atomic emission spectroscopy (ICP-AES) in screening for trace metal exposures in an industrial populationAbs: A study of trace metal concentrations in the hair and blood of an industrial population was conducted. The study group consisted of 84 male plumbers and pipe fitters, 23 to 72 years old. Blood and hair samples were collected and analyzed for lead (7439921), arsenic (7440382), chromium (7440473), zinc (7440666), selenium (7782492), cadmium (7440439), iron (7439896), nickel (7440020), copper (7440508), or aluminum (7429905) by inductively coupled plasma atomic emission spectroscopy. Samples were also analyzed for zinc-protoporphyrin to heme ratio (ZPP/heme) by hematofluorometry. Subjects completed a questionnaire detailing occupational histories and exposures to lead, arsenic, zinc, cadmium, nickel, chromium, copper, and aluminum. Eighty one percent of the cohort was White, 8.3 percent Black, 2.4 percent Asian, and 2.4 percent Native American. Sixty six subjects were actively employed. Mean blood metal concentrations were: lead, 0.41 micrograms per milliliter (microg/ml); arsenic, 0.65microg/ml; zinc, 7.92microg/ml; selenium, 0.13microg/ml; cadmium, 0.001microg/ml; iron, 528microg/ml; nickel, 0.04microg/ml; chromium, 0.55microg/ml; copper, 1.00microg/ml; and aluminum, 0.59microg/ml. Mean ZPP/heme ratio was 40.5. Mean hair metal concentrations were: lead, 32micrograms per gram (microg/g); arsenic, 1.5microg/g; zinc, 200microg/g; selenium, 2.5microg/g; cadmium, 1.7microg/g; iron, 29.1microg/g; nickel, 1.9microg/g; chromium, 3.1microg/g; copper, 49.3microg/g; and aluminum, 15.2microg/g. Only copper and chromium blood and hair concentrations were significantly positively correlated. No significant correlation between blood and hair concentrations was seen in the group reporting metal exposure versus those reporting no exposure. The authors note that the metal concentrations are comparable to those found previously in nonexposed groups. It is difficult to distinguish exposed asymptomatic workers from nonexposed workers without having detailed information on the workplace."
199,Diaz-Barriga et al. 1990,Arsenic-cadmium interaction in rats," Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.","Arsenic-cadmium interaction in ratsAbs: Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone."
200,Hochadel & Waalkes & 1997,Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer rats," Arsenic and cadmium are both priority hazardous substances and human carcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well defined. We examined the toxicity of these metals when given alone or in alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 micromol NaAsO2/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 micromol CdCl2/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortality in rats given the high dose of cadmium (9 survivors/10 treated) compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced cadmium-induced hepatotoxicity, as indicated by serum glutamic oxalacetic transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal-binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 micromol CdCl2/kg, s.c.) was given 24 h before arsenic (68, 79, 84, or 90 micro/mol NaAsO2/kg. s.c.) and toxicity was assessed 24 h later. Cadmium pretreatment did not alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhanced MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects against cadmium intoxication, and cadmium pretreatment does not effect arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to depend on the sequence of exposure.","Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer ratsAbs: Arsenic and cadmium are both priority hazardous substances and human carcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well defined. We examined the toxicity of these metals when given alone or in alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 micromol NaAsO2/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 micromol CdCl2/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortality in rats given the high dose of cadmium (9 survivors/10 treated) compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced cadmium-induced hepatotoxicity, as indicated by serum glutamic oxalacetic transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal-binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 micromol CdCl2/kg, s.c.) was given 24 h before arsenic (68, 79, 84, or 90 micro/mol NaAsO2/kg. s.c.) and toxicity was assessed 24 h later. Cadmium pretreatment did not alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhanced MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects against cadmium intoxication, and cadmium pretreatment does not effect arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to depend on the sequence of exposure."
201,Hong et al. 2004,Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population," Arsenic and cadmium are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of arsenic and cadmium, but the toxicological interactions of these inorganic mixtures are poorly defined. A general population co-exposed to arsenic and cadmium, was selected in China. The total number of participants was 245, made up of 122 in the arsenic-cadmium polluted area, 123 in the non polluted area. Urinary arsenic (UAs) and cadmium (UCd) were determined by atomic absorption spectrometry as exposure biomarkers and beta2-microglobulin (Ubeta2MG), albumin (UALB), N-acetyl-beta2-glucosaminidase (UNAG) in urine were determined as effect biomarkers. The benchmark dose (BMD) and the lower confidence limit on the benchmark dose (LBMD) were calculated to estimate the critical concentration of UAs and UCd. UAs and UCd concentrations in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The levels of Ubeta2MG, UALB and UNAG in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The BMD/LBMD of UAs and UCd for a 10% level of risk above the background level were estimated as 121.91/102.11 microg/g creatinine and 1.05/0.88 microg/g creatinine. It was suggested that the lower confidence limit of population critical concentration of UAs and UCd for renal dysfunction for 10% excess risk level above the background, which is obtained from LBMD, may need to be kept below 102 and 0.88 microg/g creatinine in order to prevent renal damage in general population co-exposed to arsenic and cadmium. It is indicated that combined effect of arsenic and cadmium were additive effect and/or synergistic effect, and cadmium may potentiate arsenic nephrotoxicity during the long-term and co-exposure to arsenic and cadmium in humans.","Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese populationAbs: Arsenic and cadmium are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of arsenic and cadmium, but the toxicological interactions of these inorganic mixtures are poorly defined. A general population co-exposed to arsenic and cadmium, was selected in China. The total number of participants was 245, made up of 122 in the arsenic-cadmium polluted area, 123 in the non polluted area. Urinary arsenic (UAs) and cadmium (UCd) were determined by atomic absorption spectrometry as exposure biomarkers and beta2-microglobulin (Ubeta2MG), albumin (UALB), N-acetyl-beta2-glucosaminidase (UNAG) in urine were determined as effect biomarkers. The benchmark dose (BMD) and the lower confidence limit on the benchmark dose (LBMD) were calculated to estimate the critical concentration of UAs and UCd. UAs and UCd concentrations in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The levels of Ubeta2MG, UALB and UNAG in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The BMD/LBMD of UAs and UCd for a 10% level of risk above the background level were estimated as 121.91/102.11 microg/g creatinine and 1.05/0.88 microg/g creatinine. It was suggested that the lower confidence limit of population critical concentration of UAs and UCd for renal dysfunction for 10% excess risk level above the background, which is obtained from LBMD, may need to be kept below 102 and 0.88 microg/g creatinine in order to prevent renal damage in general population co-exposed to arsenic and cadmium. It is indicated that combined effect of arsenic and cadmium were additive effect and/or synergistic effect, and cadmium may potentiate arsenic nephrotoxicity during the long-term and co-exposure to arsenic and cadmium in humans."
202,Basu et al. 2004,"Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: A comparative study in three cell types"," Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 +/- 9.0273 microg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 +/- 0.3157 microg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P &lt; 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.","Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: A comparative study in three cell typesAbs: Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 +/- 9.0273 microg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 +/- 0.3157 microg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P &lt; 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells."
203,Feng et al. 2001,"DNA damage in buccal epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China"," The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 ± 23.7 ?g/L (mean ± SEM) and 13 controls exposed to arsenic at 4.4 ± 1.0 ?g/L. DNA fragmentation by the DNA ladder and TUNEL assay were used to detect DNA damage in buccal cells. In the DNA ladder assay, 89% (17/19) of the arsenic-exposed group showed <100 bp DNA fragments, in contrast to 15% (2/13) of the controls ( p< 0.0001). For the TUNEL assay, the mean frequencies of positive cells were higher in the exposed group (15.1%) than in the controls (2.0%) (p<0.0001). This study showed that high arsenic exposure via drinking water resulted in DNA damage and DNA fragmentation in buccal cells thus may be an appropriate biomarker for assessing chronic effects of arsenic in humans. A study investigating DNA fragmentation from the individuals with low levels of arsenic exposure in this population is in progress.","DNA damage in buccal epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, ChinaAbs: The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 ± 23.7 ?g/L (mean ± SEM) and 13 controls exposed to arsenic at 4.4 ± 1.0 ?g/L. DNA fragmentation by the DNA ladder and TUNEL assay were used to detect DNA damage in buccal cells. In the DNA ladder assay, 89% (17/19) of the arsenic-exposed group showed <100 bp DNA fragments, in contrast to 15% (2/13) of the controls ( p< 0.0001). For the TUNEL assay, the mean frequencies of positive cells were higher in the exposed group (15.1%) than in the controls (2.0%) (p<0.0001). This study showed that high arsenic exposure via drinking water resulted in DNA damage and DNA fragmentation in buccal cells thus may be an appropriate biomarker for assessing chronic effects of arsenic in humans. A study investigating DNA fragmentation from the individuals with low levels of arsenic exposure in this population is in progress."
204,Moore et al. 1997,Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking water," Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic.","Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking waterAbs: Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic."
205,Tian et al. 2001,"Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China"," The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.","Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, ChinaAbs: The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells."
206,Mendez-Gomez et al. 2008,"Genotoxic effects of environmental exposure to arsenic and lead on children in region Lagunera, Mexico"," DNA damage and DNA repair ability by means of the comet assay and the hydrogen peroxide challenge in lymphocytes from 65 children exposed simultaneously to As and Pb in Region Lagunera, Mexico. The first exposure scenario was concerned with natural As contamination in drinking water affecting all children, particularly those attending the schools farthest from (Gomez Palacio) and closest to the smelter (Pedro Garcia). The second scenario related to additional Pb and As soil and dust contamination in the schools located in the smelter vicinity (Heroe de Nacozari and Pedro Garcia). Most children (93%) had As in urine (AsU) above 50 ?g/L and 65% had blood Pb (PbB) above 10 ?g/dL. The highest AsU median levels were observed in the school farthest from the smelter, whereas the highest PbB values were observed in the closest school. DNA damage and a decreased repair ability observed in children attending the schools were more severe than those reported for healthy Mexican children. However, the multivariate analysis did not show significant associations between DNA basal damage and PbB or AsU. Lymphocytes from 58% of the children did not respond to the peroxide challenge, and those had a more severe basal DNA damage. DNA repair capacity showed a slowed response and was negatively associated with AsU. Thus, in addition to reduced exposure, further studies are needed to ascertain if the deficiency in DNA repair is transient or if children are already displaying a mutator phenotype and are at risk of developing cancer.","Genotoxic effects of environmental exposure to arsenic and lead on children in region Lagunera, MexicoAbs: DNA damage and DNA repair ability by means of the comet assay and the hydrogen peroxide challenge in lymphocytes from 65 children exposed simultaneously to As and Pb in Region Lagunera, Mexico. The first exposure scenario was concerned with natural As contamination in drinking water affecting all children, particularly those attending the schools farthest from (Gomez Palacio) and closest to the smelter (Pedro Garcia). The second scenario related to additional Pb and As soil and dust contamination in the schools located in the smelter vicinity (Heroe de Nacozari and Pedro Garcia). Most children (93%) had As in urine (AsU) above 50 ?g/L and 65% had blood Pb (PbB) above 10 ?g/dL. The highest AsU median levels were observed in the school farthest from the smelter, whereas the highest PbB values were observed in the closest school. DNA damage and a decreased repair ability observed in children attending the schools were more severe than those reported for healthy Mexican children. However, the multivariate analysis did not show significant associations between DNA basal damage and PbB or AsU. Lymphocytes from 58% of the children did not respond to the peroxide challenge, and those had a more severe basal DNA damage. DNA repair capacity showed a slowed response and was negatively associated with AsU. Thus, in addition to reduced exposure, further studies are needed to ascertain if the deficiency in DNA repair is transient or if children are already displaying a mutator phenotype and are at risk of developing cancer."
207,Bueno de Mesquita et al. 1993,Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands," As part of the ""IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants,"" a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers.","Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The NetherlandsAbs: As part of the ""IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants,"" a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers."
208,Steenland et al. 2001,Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand data," OBJECTIVES: To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results. METHODS: Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control. RESULTS: The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI -0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population. CONCLUSIONS: There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown.","Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand dataAbs: OBJECTIVES: To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results. METHODS: Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control. RESULTS: The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI -0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population. CONCLUSIONS: There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown."
209,Heida et al. 1995,Risk assessment approach to evaluating potential remedial actions at the Diemerzeedijk hazardous waste site," As a result of the former burning of hazardous chemical wastes in the open air along the border of lake IJmeer, located southeast of Amsterdam, the surrounding environment was contaminated with a variety of organic substances. The major contaminants detected were solvents, volatile aromatics, organochlorine pesticides, arsenic, PCBs, PAHs and PCDDs/PCDFs. For the purpose of risk assessment, several pathways for the migration of hazardous substances were identified. Both site-specific total-lifetime cancer risk and total acceptable daily intake were calculated. The relative contribution of the PCDDs/PCDFs to the total acceptable daily intake was 50.1%. In addition, their contribution to the total-lifetime cancer risk amounted to more than 98%. It is concluded that without remedial action neither the total-lifetime carcinogenic risk nor the total acceptable daily intake would satisfy the minimum health protection goals of 10 super(-6) and 300%, respectively. Complete removal of the residues from burning and of the adjacent lake sediments turned out to be the remedial action plan offering the greatest degree of public health protection.","Risk assessment approach to evaluating potential remedial actions at the Diemerzeedijk hazardous waste siteAbs: As a result of the former burning of hazardous chemical wastes in the open air along the border of lake IJmeer, located southeast of Amsterdam, the surrounding environment was contaminated with a variety of organic substances. The major contaminants detected were solvents, volatile aromatics, organochlorine pesticides, arsenic, PCBs, PAHs and PCDDs/PCDFs. For the purpose of risk assessment, several pathways for the migration of hazardous substances were identified. Both site-specific total-lifetime cancer risk and total acceptable daily intake were calculated. The relative contribution of the PCDDs/PCDFs to the total acceptable daily intake was 50.1%. In addition, their contribution to the total-lifetime cancer risk amounted to more than 98%. It is concluded that without remedial action neither the total-lifetime carcinogenic risk nor the total acceptable daily intake would satisfy the minimum health protection goals of 10 super(-6) and 300%, respectively. Complete removal of the residues from burning and of the adjacent lake sediments turned out to be the remedial action plan offering the greatest degree of public health protection."
210,Ansaldo et al. 2009,"Effect of cadmium, lead and arsenic on the oviposition, hatching and embryonic survival of Biomphalaria glabrata"," Biomphalaria glabrata is a widespread freshwater gastropod mollusc. The easy aquaculture of these organisms allow its use as an accessible tool for contamination bioassays. B. glabrata showed marked metabolic responses when exposed to cadmium, lead and arsenic. Those responses could also affect the reproduction of the snails. Taking into account this hypothesis, B. glabrata were exposed for 96 h (acute laboratory bioassays) to different concentrations of cadmium (0.1, 0.05 and 0 mg/L), lead (0.5, 0.1, 0.05 and 0 mg/L) and arsenic (0.5, 0.1, 0.05 and 0 mg/L). Snails were removed from the aquaria while eggs were left in the same contaminant concentrations. The effect of the assayed toxicants on snail reproduction was registered as the alterations of the total number of laid eggs (TNLE), hatching time and embryonic survival. At 0.10 mg/L cadmium significantly decreased the TNLE (p<0.05) and no embryos survived. The lowest assayed level (0.05 mg/L) of cadmium, delayed the hatching time twice when it was compared with the control group (p<0.01). Lead decreased the TNLE at 0.5 mg/L level (p<0.01). The other assayed doses (0.05 and 0.10 mg/L) also decreased embryonic survival significantly (p<0.05 and p<0.01 respectively) and extended twice the time to hatching (p<0.01). The 0.50 mg/L level killed all embryos. Arsenic at all studied concentrations decreased the TNLE (p<0.05) while the hatching time was increased by 50%. Embryo survival only decreased at the highest level (0.5 mg/L) of arsenic assayed. In summary, the acute exposure (96 h) to cadmium lead and arsenic, altered the reproduction of B. glabrata, modifying the TNLE, hatching time and embryonic survival.","Effect of cadmium, lead and arsenic on the oviposition, hatching and embryonic survival of Biomphalaria glabrataAbs: Biomphalaria glabrata is a widespread freshwater gastropod mollusc. The easy aquaculture of these organisms allow its use as an accessible tool for contamination bioassays. B. glabrata showed marked metabolic responses when exposed to cadmium, lead and arsenic. Those responses could also affect the reproduction of the snails. Taking into account this hypothesis, B. glabrata were exposed for 96 h (acute laboratory bioassays) to different concentrations of cadmium (0.1, 0.05 and 0 mg/L), lead (0.5, 0.1, 0.05 and 0 mg/L) and arsenic (0.5, 0.1, 0.05 and 0 mg/L). Snails were removed from the aquaria while eggs were left in the same contaminant concentrations. The effect of the assayed toxicants on snail reproduction was registered as the alterations of the total number of laid eggs (TNLE), hatching time and embryonic survival. At 0.10 mg/L cadmium significantly decreased the TNLE (p<0.05) and no embryos survived. The lowest assayed level (0.05 mg/L) of cadmium, delayed the hatching time twice when it was compared with the control group (p<0.01). Lead decreased the TNLE at 0.5 mg/L level (p<0.01). The other assayed doses (0.05 and 0.10 mg/L) also decreased embryonic survival significantly (p<0.05 and p<0.01 respectively) and extended twice the time to hatching (p<0.01). The 0.50 mg/L level killed all embryos. Arsenic at all studied concentrations decreased the TNLE (p<0.05) while the hatching time was increased by 50%. Embryo survival only decreased at the highest level (0.5 mg/L) of arsenic assayed. In summary, the acute exposure (96 h) to cadmium lead and arsenic, altered the reproduction of B. glabrata, modifying the TNLE, hatching time and embryonic survival."
211,Anwar 2005,"Arsenic, cadmium and lead levels in hair and toenail samples in pakistan"," We collected toenail and hair samples from 160 subjects, 83 males and 77 females, residing in Lahore city and its suburban areas in Pakistan, and examined the concentrations of arsenic, cadmium, lead and other metals using inductively coupled plasma mass spectrometry (ICP-MS). The mean hair and toenail arsenic levels were 0.31 ppm and 0.70 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail arsenic levels was 0.16 (p=0.051). After excluding a subject with hair and toenail arsenic levels as high as 1.12 ppm and 4.72 ppm, respectively, the correlation coefficient was 0.27 (p=0.001). Arsenic levels observed in the present study were relatively higher than in most developed countries. Hair or toenail arsenic concentration was not affected by sex, area of origin, place of residence and education, but toenail arsenic levels increased with age (p=0.029). Fish consumption was inversely related to arsenic levels, suggesting that consumption of beans , which are the main staple of poor people living in the study area who cannot afford to eat fish frequently, may be the source of arsenic exposure among the residents of Lahore and its suburban areas. The mean hair and toenail cadmium levels in the present study were 0.08 ppm and 0.05 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail cadmium levels was 0.17 (p=0.034). Cadmium levels were lower compared to those reported from developed countries, including Japan. The mean hair and toenail lead levels were 3.53 ppm and 2.11 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail lead levels was 0.15, which was not statistically significant (p=0.055). When a female subject with toenail lead of 52.4 ppm was excluded, the correlation was 0.17 (p=0.036). Lead levels observed in the present study were similar to those reported from developed countries. In the present study, relatively high lead toenail values were observed among children. The levels of cadmium and lead in hair but not in toenails were higher among those living in central Lahore than among those living outside Lahore, suggesting that dust containing those heavy metals was attached to hair samples due to a typical urban environment with heavy traffic load, congested population and industrial activities.","Arsenic, cadmium and lead levels in hair and toenail samples in pakistanAbs: We collected toenail and hair samples from 160 subjects, 83 males and 77 females, residing in Lahore city and its suburban areas in Pakistan, and examined the concentrations of arsenic, cadmium, lead and other metals using inductively coupled plasma mass spectrometry (ICP-MS). The mean hair and toenail arsenic levels were 0.31 ppm and 0.70 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail arsenic levels was 0.16 (p=0.051). After excluding a subject with hair and toenail arsenic levels as high as 1.12 ppm and 4.72 ppm, respectively, the correlation coefficient was 0.27 (p=0.001). Arsenic levels observed in the present study were relatively higher than in most developed countries. Hair or toenail arsenic concentration was not affected by sex, area of origin, place of residence and education, but toenail arsenic levels increased with age (p=0.029). Fish consumption was inversely related to arsenic levels, suggesting that consumption of beans , which are the main staple of poor people living in the study area who cannot afford to eat fish frequently, may be the source of arsenic exposure among the residents of Lahore and its suburban areas. The mean hair and toenail cadmium levels in the present study were 0.08 ppm and 0.05 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail cadmium levels was 0.17 (p=0.034). Cadmium levels were lower compared to those reported from developed countries, including Japan. The mean hair and toenail lead levels were 3.53 ppm and 2.11 ppm, respectively. The correlation coefficient between log-transformed values of hair and toenail lead levels was 0.15, which was not statistically significant (p=0.055). When a female subject with toenail lead of 52.4 ppm was excluded, the correlation was 0.17 (p=0.036). Lead levels observed in the present study were similar to those reported from developed countries. In the present study, relatively high lead toenail values were observed among children. The levels of cadmium and lead in hair but not in toenails were higher among those living in central Lahore than among those living outside Lahore, suggesting that dust containing those heavy metals was attached to hair samples due to a typical urban environment with heavy traffic load, congested population and industrial activities."
212,Bishayi and Sengupta 2006,Synergism in immunotoxicological effects due to repeated combined administration of arsenic and lead in mice," Arsenic and lead are considered potent human hazards because of their neoplastic outcomes; increasing epidemiologic evidence indicates a link between heavy metal exposure and health risk. Since health risks of singly administered metals are well-established, in the present study we determined whether simultaneous repeated multimetal (arsenic + lead) exposure influences the development of immunotoxicity in mice exposed (in vivo) to lead acetate (10 mg/kg b.w.) and sodium arsenite (0.5 mg/kg b.w.) simultaneously. We report that in vivo multimetal exposure alters cell morphology, inhibits cell adhesion, nitric oxide release, intracellular killing ability, chemotactic migration, myeloperoxidase release, bacterial clearance from blood and spleen and increases DNA fragmentation. On measuring bacterial density in blood and spleen after 0, 24, 48 and 72 h post infection (with Staphylococcus aureus MC524) in control and multimetal treated groups, bacterial load showed delayed clearance from blood and spleen in the multimetal exposed group. We also found that in vivo exposure to the multimetal caused a decrease in cell adhesion, indicated by a fall in absorbance at 570 nm with respect to control. Exposure to multimetal led to morphological changes in macrophages, since more deformed cells were obtained in repeated combined exposure to arsenic and lead compared to control. Nitric oxide, which has a potent microbicidal activity in macrophages, was found to be released in fewer amounts in the multimetal exposed group from that of control group. It was observed that the viability of bacteria gradually decreased in control macrophage with time, whereas, in macrophages of multimetal exposed mice, the viability of S. aureus gradually increased. Chemotactic migration of splenic macrophages significantly decreased in the multimetal exposed group from that of control. Lysosomal enzyme release from splenic macrophages decreased upon simultaneous exposure to arsenic and lead, as is evident from the decrease in myeloperoxidase release in multimetal group from that in control. That the structural integrity of splenic macrophages is decreased in the multimetal exposed group is also evident from the enhanced percentage of DNA fragmentation after multimetal exposure, suggesting apoptotic death of splenic macrophage. Intracellular viable bacteria in the splenic macrophage from multimetal exposed group was 89.16Â±3.54% while that from control group was 49.19Â±1.16%, whereas single metal exposed groups showed a bacterial viability of 69.6Â±2.45% and 71.71Â±1.89% in arsenic and lead treated groups respectively. What is essentially noteworthy from the observed results is that lead and arsenic causes a greater immunotoxic effect when administered together as multimetal than when singly administered. Simultaneous exposure to lead and arsenic appears to be additive as is further established from the isobologram constructed by plotting the concentration of arsenic against the concentration of lead at which effect (in this case myeloperoxidase release) remained constant, a convex line showing synergism was demonstrated. The present study reports a definite synergistic trend of immunotoxicity during simultaneous exposure to arsenic and lead, that is, a multimetal challenge, as compared to the effects of independent exposure to them.","Synergism in immunotoxicological effects due to repeated combined administration of arsenic and lead in miceAbs: Arsenic and lead are considered potent human hazards because of their neoplastic outcomes; increasing epidemiologic evidence indicates a link between heavy metal exposure and health risk. Since health risks of singly administered metals are well-established, in the present study we determined whether simultaneous repeated multimetal (arsenic + lead) exposure influences the development of immunotoxicity in mice exposed (in vivo) to lead acetate (10 mg/kg b.w.) and sodium arsenite (0.5 mg/kg b.w.) simultaneously. We report that in vivo multimetal exposure alters cell morphology, inhibits cell adhesion, nitric oxide release, intracellular killing ability, chemotactic migration, myeloperoxidase release, bacterial clearance from blood and spleen and increases DNA fragmentation. On measuring bacterial density in blood and spleen after 0, 24, 48 and 72 h post infection (with Staphylococcus aureus MC524) in control and multimetal treated groups, bacterial load showed delayed clearance from blood and spleen in the multimetal exposed group. We also found that in vivo exposure to the multimetal caused a decrease in cell adhesion, indicated by a fall in absorbance at 570 nm with respect to control. Exposure to multimetal led to morphological changes in macrophages, since more deformed cells were obtained in repeated combined exposure to arsenic and lead compared to control. Nitric oxide, which has a potent microbicidal activity in macrophages, was found to be released in fewer amounts in the multimetal exposed group from that of control group. It was observed that the viability of bacteria gradually decreased in control macrophage with time, whereas, in macrophages of multimetal exposed mice, the viability of S. aureus gradually increased. Chemotactic migration of splenic macrophages significantly decreased in the multimetal exposed group from that of control. Lysosomal enzyme release from splenic macrophages decreased upon simultaneous exposure to arsenic and lead, as is evident from the decrease in myeloperoxidase release in multimetal group from that in control. That the structural integrity of splenic macrophages is decreased in the multimetal exposed group is also evident from the enhanced percentage of DNA fragmentation after multimetal exposure, suggesting apoptotic death of splenic macrophage. Intracellular viable bacteria in the splenic macrophage from multimetal exposed group was 89.16Â±3.54% while that from control group was 49.19Â±1.16%, whereas single metal exposed groups showed a bacterial viability of 69.6Â±2.45% and 71.71Â±1.89% in arsenic and lead treated groups respectively. What is essentially noteworthy from the observed results is that lead and arsenic causes a greater immunotoxic effect when administered together as multimetal than when singly administered. Simultaneous exposure to lead and arsenic appears to be additive as is further established from the isobologram constructed by plotting the concentration of arsenic against the concentration of lead at which effect (in this case myeloperoxidase release) remained constant, a convex line showing synergism was demonstrated. The present study reports a definite synergistic trend of immunotoxicity during simultaneous exposure to arsenic and lead, that is, a multimetal challenge, as compared to the effects of independent exposure to them."
213,Wilhelma et al. 2006,"Revised and new reference values for arsenic, cadmium, lead and mercury in blood or urine of children. Basis for validation of human biomonitoring data in environmental medicine"," Reference values for environmental pollutants in the German population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency. The reference values (defined as 95th percentile) are usually derived from results of the German Environmental Surveys (GerES). However, current reference values for children are lacking since GerES II conducted in 1990/92 and additionally the first German Environmental Survey on Children (GerES IV) will not be finished until the end of 2006. As an interim solution, the commission derived in 2005 reference values for children aged 6–12 years from a survey performed in south-west Germany in 2002/03 (508 children) and the pilot study for GerES IV 2001/2002 (252 children). A new reference value of 15 mg/l for children was derived for arsenic in urine. The reference values for cadmium in whole blood (0.5 mg/l) and for cadmium in urine (0.5 mg/l) were confirmed. The following reference values were lowered: for lead in blood from 60 to 50 mg/l, for mercury in whole blood from 1.5 to 1.0 mg/l and for mercury in urine from 1.4 to 0.7 mg/l.","Revised and new reference values for arsenic, cadmium, lead and mercury in blood or urine of children. Basis for validation of human biomonitoring data in environmental medicineAbs: Reference values for environmental pollutants in the German population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency. The reference values (defined as 95th percentile) are usually derived from results of the German Environmental Surveys (GerES). However, current reference values for children are lacking since GerES II conducted in 1990/92 and additionally the first German Environmental Survey on Children (GerES IV) will not be finished until the end of 2006. As an interim solution, the commission derived in 2005 reference values for children aged 6–12 years from a survey performed in south-west Germany in 2002/03 (508 children) and the pilot study for GerES IV 2001/2002 (252 children). A new reference value of 15 mg/l for children was derived for arsenic in urine. The reference values for cadmium in whole blood (0.5 mg/l) and for cadmium in urine (0.5 mg/l) were confirmed. The following reference values were lowered: for lead in blood from 60 to 50 mg/l, for mercury in whole blood from 1.5 to 1.0 mg/l and for mercury in urine from 1.4 to 0.7 mg/l."
214,Nwajei and Iwegbue 2007,"Trace elements in sawdust particles in the vicinity of sawmill in Sapele, Nigeria"," This study report the results of determination of concentrations of lead, cadmium, chromium, barium, arsenic and mercury in sawdust particles collected in the vicinity of wood sawmill in Sapele, Nigeria and its environs. The mean levels of the elements observed ranged from 40-250 mg kg-1 for Pb; 0.50 mg kg-1 for Cd; 1.46-160.50 mg kg-1 for Cr; 1.50-94.0 mg kg-1 for Ba; 32.0-84.0 mg kg-1 for As and 0.50-40 mg kg-1 for Hg. The levels of these trace elements observed in the sawdust particles exceeded permissible occupational exposure limits. Sawdust particles constitute serious health risk to human and the environment in general.","Trace elements in sawdust particles in the vicinity of sawmill in Sapele, NigeriaAbs: This study report the results of determination of concentrations of lead, cadmium, chromium, barium, arsenic and mercury in sawdust particles collected in the vicinity of wood sawmill in Sapele, Nigeria and its environs. The mean levels of the elements observed ranged from 40-250 mg kg-1 for Pb; 0.50 mg kg-1 for Cd; 1.46-160.50 mg kg-1 for Cr; 1.50-94.0 mg kg-1 for Ba; 32.0-84.0 mg kg-1 for As and 0.50-40 mg kg-1 for Hg. The levels of these trace elements observed in the sawdust particles exceeded permissible occupational exposure limits. Sawdust particles constitute serious health risk to human and the environment in general."
215,Engstrom et al. 2010,"Chronic exposure to cadmium and arsenic strongly influences concentrations of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urine"," Exposure to arsenic (As), cadmium (Cd) and lead (Pb) may generate oxidative stress, which can be assessed by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, a sensitive marker of oxidatively damaged DNA. We have evaluated oxidative stress induced by mixed chronic exposure to As, Cd, Pb, as well as the influence of As metabolism and nutritional status, i.e. ferritin (Ft), selenium (Se), zinc (Zn), manganese (Mn) and body weight. 8-oxodG was measured in urine from 212 women in early pregnancy from Matlab, rural Bangladesh, using LC-MS/MS. Cd and Pb were analyzed in urine and erythrocytes, while Se, Mn and Zn were analyzed in erythrocytes, all by ICPMS. As and As metabolites were analyzed in urine by HPLC-ICPMS. Ferritin was analyzed in plasma by radioimmunoassay. Median concentration of 8-oxodG was 8.3 nmol/L (adjusted for specific gravity), range 1.2-43, corresponding to a median of 4.7 mug/g creatinine, range 1.8-32. 8-oxodG was positively associated with urinary Cd (ss=0.32, p<0.001), urinary As (ss=0.0007, p=0.001), fraction of the monomethylated arsenic metabolite (MMA) in urine (ss=0.0026, p=0.004) and plasma Ft (ss = 0.20, p<0.001). A joint effect was seen for U-Cd and U-As, but whether this effect was additive or multiplicative was difficult to discern.","Chronic exposure to cadmium and arsenic strongly influences concentrations of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urineAbs: Exposure to arsenic (As), cadmium (Cd) and lead (Pb) may generate oxidative stress, which can be assessed by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, a sensitive marker of oxidatively damaged DNA. We have evaluated oxidative stress induced by mixed chronic exposure to As, Cd, Pb, as well as the influence of As metabolism and nutritional status, i.e. ferritin (Ft), selenium (Se), zinc (Zn), manganese (Mn) and body weight. 8-oxodG was measured in urine from 212 women in early pregnancy from Matlab, rural Bangladesh, using LC-MS/MS. Cd and Pb were analyzed in urine and erythrocytes, while Se, Mn and Zn were analyzed in erythrocytes, all by ICPMS. As and As metabolites were analyzed in urine by HPLC-ICPMS. Ferritin was analyzed in plasma by radioimmunoassay. Median concentration of 8-oxodG was 8.3 nmol/L (adjusted for specific gravity), range 1.2-43, corresponding to a median of 4.7 mug/g creatinine, range 1.8-32. 8-oxodG was positively associated with urinary Cd (ss=0.32, p<0.001), urinary As (ss=0.0007, p=0.001), fraction of the monomethylated arsenic metabolite (MMA) in urine (ss=0.0026, p=0.004) and plasma Ft (ss = 0.20, p<0.001). A joint effect was seen for U-Cd and U-As, but whether this effect was additive or multiplicative was difficult to discern."
216,Lopes et al. 2010,European bee-eater (Merops apiaster) populations under arsenic and metal stress: evaluation of exposure at a mining site," Two populations of the European bee-eater were studied, one living at a reference site and the other at a metal mining site. The concentration of arsenic and 11 metals (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) was measured in feathers and regurgitated pellets collected at both sites. Cadmium, chromium, mercury, nickel, and lead were at least twofold higher in feathers of birds from the contaminated site than in the reference site, suggesting that this population was exposed to higher metal levels. Similarly, levels of aluminum, arsenic, cadmium, cobalt, chromium, iron, and lead were also at least twofold higher in pellets from the contaminated area. The obtained results suggested that the impacted population of Merops apiaster is at risk due to the exposure to some metals.","European bee-eater (Merops apiaster) populations under arsenic and metal stress: evaluation of exposure at a mining siteAbs: Two populations of the European bee-eater were studied, one living at a reference site and the other at a metal mining site. The concentration of arsenic and 11 metals (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) was measured in feathers and regurgitated pellets collected at both sites. Cadmium, chromium, mercury, nickel, and lead were at least twofold higher in feathers of birds from the contaminated site than in the reference site, suggesting that this population was exposed to higher metal levels. Similarly, levels of aluminum, arsenic, cadmium, cobalt, chromium, iron, and lead were also at least twofold higher in pellets from the contaminated area. The obtained results suggested that the impacted population of Merops apiaster is at risk due to the exposure to some metals."
217,Nise et al. 2010,Epigenetics: origins and implications for cancer epidemiology," This paper provides information on the evolution of the 'epigenetics' concept since Aristotle and draws attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical arguments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond 'pristine' inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollution, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes.","Epigenetics: origins and implications for cancer epidemiologyAbs: This paper provides information on the evolution of the 'epigenetics' concept since Aristotle and draws attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical arguments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond 'pristine' inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollution, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes."
218,Zarazua et al. 2010,Decreased arginine methylation and myelin alterations in arsenic exposed rats," Methylation has an important role in the synthesis of myelin basic protein (MBP), an essential component that confers compactness to myelin, and the correct synthesis and assembling of myelin are fundamental in the development of the central nervous system. Since arsenic metabolism requires a high consumption of S-adenosylmethionine, the main donor of methyl groups in the organism, it has been proposed that arsenic exposure can lead to a demethylation status in the organism comprising DNA and protein hypomethylation. This study documents myelin alterations in brain and changes in levels of methylated arginines in brain and serum of adult female Wistar rats exposed to arsenic (3 and 36 ppm, drinking water) from gestation throughout lactation, development and until 1, 2, 3 and 4 months of age. Morphological characteristics were analyzed by means of light microscopy and methylated arginines were analyzed through HPLC. Arsenic intake resulted in myelin damage reflected as empty spaces in fiber tracts of the exposed animals. The low exposure group (approximately 0.4 mg/kg/day) did not present myelin damage during the first 2 months, only moderate alterations in the third and fourth months. By contrast, animals exposed to 36 ppm (approximately 4 mg/kg/day) showed moderate to severe damage to nerve tracts from the first month of age. These alterations were accompanied by significant lower levels of dimethyl arginine in both exposed groups, as compared with the controls, in the third and fourth months of age and exposure. These data demonstrate that myelin composition is a target of arsenic through interference with arginine methylation, and they suggest that disturbances in nervous transmission through myelinated fibers are an important component of arsenic neurotoxicity.","Decreased arginine methylation and myelin alterations in arsenic exposed ratsAbs: Methylation has an important role in the synthesis of myelin basic protein (MBP), an essential component that confers compactness to myelin, and the correct synthesis and assembling of myelin are fundamental in the development of the central nervous system. Since arsenic metabolism requires a high consumption of S-adenosylmethionine, the main donor of methyl groups in the organism, it has been proposed that arsenic exposure can lead to a demethylation status in the organism comprising DNA and protein hypomethylation. This study documents myelin alterations in brain and changes in levels of methylated arginines in brain and serum of adult female Wistar rats exposed to arsenic (3 and 36 ppm, drinking water) from gestation throughout lactation, development and until 1, 2, 3 and 4 months of age. Morphological characteristics were analyzed by means of light microscopy and methylated arginines were analyzed through HPLC. Arsenic intake resulted in myelin damage reflected as empty spaces in fiber tracts of the exposed animals. The low exposure group (approximately 0.4 mg/kg/day) did not present myelin damage during the first 2 months, only moderate alterations in the third and fourth months. By contrast, animals exposed to 36 ppm (approximately 4 mg/kg/day) showed moderate to severe damage to nerve tracts from the first month of age. These alterations were accompanied by significant lower levels of dimethyl arginine in both exposed groups, as compared with the controls, in the third and fourth months of age and exposure. These data demonstrate that myelin composition is a target of arsenic through interference with arginine methylation, and they suggest that disturbances in nervous transmission through myelinated fibers are an important component of arsenic neurotoxicity."
219,Bae et al. 2007,Arsenite-Enhanced Procoagulant Activity through Phosphatidylserine Exposure in Platelets," Numerous epidemiological studies have reported the close relationship between arsenic in drinking water and cardiovascular disease (CVD), yet the exact mechanism underlying this relationship remains unclear. We investigated whether arsenic can affect the procoagulant activity of platelets, which are essential in blood clotting, thrombus formation, and progression of CVD. While arsenite alone did not induce procoagulant activity, it significantly enhanced thrombin-induced procoagulant activity of human platelets in a concentration- and time-dependent manner. In flow cytometric analysis, arsenite potentiated phosphatidylserine (PS) exposure and microparticle (MP) formation, the major mediators of procoagulant activity. Arsenite-enhanced calcium increase and subsequent calpain activation were found to be involved in these effects, as determined by confocal microscopy and gel electrophoresis. Arsenite also inhibited flippase, an enzyme that restores PS to the inner leaflet, suggesting that PS could be retained in outer membranes after exposure. Consistent with these in vitro results, ex vivo studies revealed that PS exposure in platelets was significantly increased after acute or chronic arsenic exposure in rats. Most notably, in a rodent in vivo venous thrombosis model, arsenite indeed led to increased thrombus formation. In conclusion, arsenite-enhanced procoagulant activity in platelets by PS exposure and MP generation ultimately results in accelerated thrombus formation in vivo, suggesting that this enhanced activity is a possible contributing factor in CVD associated with chronic exposure to arsenic through drinking water.","Arsenite-Enhanced Procoagulant Activity through Phosphatidylserine Exposure in PlateletsAbs: Numerous epidemiological studies have reported the close relationship between arsenic in drinking water and cardiovascular disease (CVD), yet the exact mechanism underlying this relationship remains unclear. We investigated whether arsenic can affect the procoagulant activity of platelets, which are essential in blood clotting, thrombus formation, and progression of CVD. While arsenite alone did not induce procoagulant activity, it significantly enhanced thrombin-induced procoagulant activity of human platelets in a concentration- and time-dependent manner. In flow cytometric analysis, arsenite potentiated phosphatidylserine (PS) exposure and microparticle (MP) formation, the major mediators of procoagulant activity. Arsenite-enhanced calcium increase and subsequent calpain activation were found to be involved in these effects, as determined by confocal microscopy and gel electrophoresis. Arsenite also inhibited flippase, an enzyme that restores PS to the inner leaflet, suggesting that PS could be retained in outer membranes after exposure. Consistent with these in vitro results, ex vivo studies revealed that PS exposure in platelets was significantly increased after acute or chronic arsenic exposure in rats. Most notably, in a rodent in vivo venous thrombosis model, arsenite indeed led to increased thrombus formation. In conclusion, arsenite-enhanced procoagulant activity in platelets by PS exposure and MP generation ultimately results in accelerated thrombus formation in vivo, suggesting that this enhanced activity is a possible contributing factor in CVD associated with chronic exposure to arsenic through drinking water."
220,Santner et al. 2008,Demographic and Behavioral Modifiers of Arsenic Exposure Pathways: A Bayesian Hierarchical Analysis of NHEXAS Data, A Bayesian analysis of the NHEXAS data provides subpopulation-specific pathways of arsenic exposure.,Demographic and Behavioral Modifiers of Arsenic Exposure Pathways: A Bayesian Hierarchical Analysis of NHEXAS DataAbs: A Bayesian analysis of the NHEXAS data provides subpopulation-specific pathways of arsenic exposure.
221,Afridi et al. 2009,"Evaluation of arsenic, cobalt, copper and manganese in biological samples of steel mill workers by electrothermal atomic absorption spectrometry"," The determination of trace and toxic elements in biological samples (blood, urine and scalp hair samples) of human beings is an important clinical test. The aim of our present study was to determine the concentration of arsenic (As), copper (Cu), cobalt (Co) and manganese (Mn), in biological samples of male production workers (PW) and quality control workers (QW) of steel mill, with aged 25-55 years, to assess the possible influence of environmental exposure. For comparison purpose, the same biological samples of unexposed healthy mates of same age group were collected as control subjects. The determination of all elements in biological samples was carried out by electrothermal atomic absorption spectrometry, prior to microwave assisted acid digestion. The accuracy of the As, Cu, Co and Mn measurements was tested by simultaneously analyzing certified reference materials (CRMs) and for comparative purposes conventional wet acid digestion method was used on the same CRMs. No significant differences were observed between the analytical results and the certified values, using both methods (paired t-test at P > 0.05). The results indicate that concentrations of As, Cu, Co and Mn in all three biological samples of the exposed workers (QW and PW) were significantly higher than those of the controls. The possible correlation of these elements with the etiology of different physiological disorders is discussed. The results were also demonstrated the need of attention for improvements in workplace, ventilation and industrial hygiene practices. Toxicology and Industrial Health 2009; 25: 59-69.","Evaluation of arsenic, cobalt, copper and manganese in biological samples of steel mill workers by electrothermal atomic absorption spectrometryAbs: The determination of trace and toxic elements in biological samples (blood, urine and scalp hair samples) of human beings is an important clinical test. The aim of our present study was to determine the concentration of arsenic (As), copper (Cu), cobalt (Co) and manganese (Mn), in biological samples of male production workers (PW) and quality control workers (QW) of steel mill, with aged 25-55 years, to assess the possible influence of environmental exposure. For comparison purpose, the same biological samples of unexposed healthy mates of same age group were collected as control subjects. The determination of all elements in biological samples was carried out by electrothermal atomic absorption spectrometry, prior to microwave assisted acid digestion. The accuracy of the As, Cu, Co and Mn measurements was tested by simultaneously analyzing certified reference materials (CRMs) and for comparative purposes conventional wet acid digestion method was used on the same CRMs. No significant differences were observed between the analytical results and the certified values, using both methods (paired t-test at P > 0.05). The results indicate that concentrations of As, Cu, Co and Mn in all three biological samples of the exposed workers (QW and PW) were significantly higher than those of the controls. The possible correlation of these elements with the etiology of different physiological disorders is discussed. The results were also demonstrated the need of attention for improvements in workplace, ventilation and industrial hygiene practices. Toxicology and Industrial Health 2009; 25: 59-69."
222,Aguirre-Banuelos et al. 2008,Inorganic arsenic exposure affects pain behavior and inflammatory response in rat," Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem associated with an increased risk for the development of various types of cancer and noncancerous damage. In vitro studies have suggested that iAs can modulate the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX-2) and resulting in an increase in prostaglandin E-2 (PGE(2)) concentrations in endothelial cells. These effects may lead to an in vivo enhancement of inflammatory and pain responses. Our aim was to determine the effect of a single dose of arsenic or subchronic exposure to arsenic on pain behavior and tissue inflammation in rats. Rats were given a single dose of sodium arsenite (0.1, 1 and 10 mg/kg i.p.) or submitted to subchronic exposure to arsenic added to the drinking water for 4 weeks (0.1, 1, 10 and 100 ppm). Inflammatory pain was assessed by using the formalin and tail-flick tests, while inflammation was evaluated with the carrageenan model. Arsenite did not induce pain or significant inflammation by itself. In contrast, arsenite in both single dose administration and subchronic exposure increased not only the inflammatory process and the underlying hyperalgesic pain, but also induced a decrease in the pain threshold. Alterations in pain processing were dependent on the arsenic dose and the length of exposure, and the underlying mechanism involved an increased release of local PGE2. These results suggest that inorganic arsenic exposure enhances pain perception and exacerbates the pathological state of inflammatory diseases. (c) 2008 Elsevier Inc. All rights reserved.","Inorganic arsenic exposure affects pain behavior and inflammatory response in ratAbs: Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem associated with an increased risk for the development of various types of cancer and noncancerous damage. In vitro studies have suggested that iAs can modulate the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX-2) and resulting in an increase in prostaglandin E-2 (PGE(2)) concentrations in endothelial cells. These effects may lead to an in vivo enhancement of inflammatory and pain responses. Our aim was to determine the effect of a single dose of arsenic or subchronic exposure to arsenic on pain behavior and tissue inflammation in rats. Rats were given a single dose of sodium arsenite (0.1, 1 and 10 mg/kg i.p.) or submitted to subchronic exposure to arsenic added to the drinking water for 4 weeks (0.1, 1, 10 and 100 ppm). Inflammatory pain was assessed by using the formalin and tail-flick tests, while inflammation was evaluated with the carrageenan model. Arsenite did not induce pain or significant inflammation by itself. In contrast, arsenite in both single dose administration and subchronic exposure increased not only the inflammatory process and the underlying hyperalgesic pain, but also induced a decrease in the pain threshold. Alterations in pain processing were dependent on the arsenic dose and the length of exposure, and the underlying mechanism involved an increased release of local PGE2. These results suggest that inorganic arsenic exposure enhances pain perception and exacerbates the pathological state of inflammatory diseases. (c) 2008 Elsevier Inc. All rights reserved."
223,Amster et al. 2007,Case report: Potential arsenic toxicosis secondary to herbal kelp supplement," CONTEXT: Medicinal use of dietary herbal supplements can cause inadvertent arsenic toxicosis. CASE PRESENTATION: A 54-year-old woman was referred to the University of California, Davis, Occupational Medicine Clinic with a 2-year history of worsening alopecia and memory loss. She also reported having a rash, increasing fatigue, nausea, and vomiting, disabling her to the point where she could no longer work full-time. A thorough exposure history revealed that she took daily kelp supplements. A urine sample showed an arsenic level of 83.6 mu g/g creatinine (normal < 50 mu g/g creatinine). A sample from her kelp supplements contained 8.5 mg/kg (ppm) arsenic. Within weeks of discontinuing the supplements, her symptoms resolved and arsenic blood and urine levels were undetectable. DISCUSSION: To evaluate the extent of arsenic contamination in commercially available kelp, we analyzed nine samples randomly obtained from local health food stores. Eight of the nine samples showed detectable levels of arsenic higher than the Food and Drug Administration tolerance level of 0.5 to 2 ppm for certain food products. None of the supplements contained information regarding the possibility of contamination with arsenic or other heavy metals. The 1994 Dietary Supplement Health and Education Act (DSHEA) has changed the way dietary herbal therapies are marketed and regulated in the United States. Less regulation of dietary herbal therapies will make inadvertent toxicities a more frequent occurrence. RELEVANCE TO CLINICAL PRACTICE: Clinicians should be aware of the potential for heavy metal toxicity due to chronic use of dietary herbal supplements. Inquiring about use of dietary supplements is an important element of the medical history.","Case report: Potential arsenic toxicosis secondary to herbal kelp supplementAbs: CONTEXT: Medicinal use of dietary herbal supplements can cause inadvertent arsenic toxicosis. CASE PRESENTATION: A 54-year-old woman was referred to the University of California, Davis, Occupational Medicine Clinic with a 2-year history of worsening alopecia and memory loss. She also reported having a rash, increasing fatigue, nausea, and vomiting, disabling her to the point where she could no longer work full-time. A thorough exposure history revealed that she took daily kelp supplements. A urine sample showed an arsenic level of 83.6 mu g/g creatinine (normal < 50 mu g/g creatinine). A sample from her kelp supplements contained 8.5 mg/kg (ppm) arsenic. Within weeks of discontinuing the supplements, her symptoms resolved and arsenic blood and urine levels were undetectable. DISCUSSION: To evaluate the extent of arsenic contamination in commercially available kelp, we analyzed nine samples randomly obtained from local health food stores. Eight of the nine samples showed detectable levels of arsenic higher than the Food and Drug Administration tolerance level of 0.5 to 2 ppm for certain food products. None of the supplements contained information regarding the possibility of contamination with arsenic or other heavy metals. The 1994 Dietary Supplement Health and Education Act (DSHEA) has changed the way dietary herbal therapies are marketed and regulated in the United States. Less regulation of dietary herbal therapies will make inadvertent toxicities a more frequent occurrence. RELEVANCE TO CLINICAL PRACTICE: Clinicians should be aware of the potential for heavy metal toxicity due to chronic use of dietary herbal supplements. Inquiring about use of dietary supplements is an important element of the medical history."
224,Andrew et al. 2008,Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a US population," BACKGROUND: Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 mu g/L in the northeastern, western, and north central regions of the United States. OBJECTIVES: We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. METHODS: We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999-2002) as part of a case-control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. RESULTS: The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. CONCLUSIONS: These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases.","Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a US populationAbs: BACKGROUND: Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 mu g/L in the northeastern, western, and north central regions of the United States. OBJECTIVES: We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. METHODS: We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999-2002) as part of a case-control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. RESULTS: The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. CONCLUSIONS: These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases."
225,Aziz et al. 2006,"Knowledge of arsenic in drinking-water: Risks and avoidance in Matlab, Bangladesh"," Widespread contamination of arsenic in Bangladesh has been jeopardizing the health of millions of people. Residents of Matlab, Bangladesh, are among the millions at risk. Using bivariate models in the analysis of survey data, knowledge of health risks and avoidance of arsenic exposure in response to widespread contamination of arsenic for residents of Matlab were estimated. The models examined individuals' knowledge of an arsenic problem in the household and knowledge of specific illnesses caused by arsenic exposure. The likelihood of avoiding exposure to arsenic contamination was further examined. Results of the estimation showed that individual's knowledge of arsenic problems in the household was gathered through awareness campaigns and by word of mouth and that knowledge of illnesses was predicated on education, health, presence of children, elderly and young women. Adoption of avoidance measures was not affected by exposure to arsenic-information sources, but level of education had a statistically significant positive effect on the decision to avoid arsenic exposure. Lack of convenience of safe drinking-water practices lead people to persist in drinking arsenic-contaminated water.","Knowledge of arsenic in drinking-water: Risks and avoidance in Matlab, BangladeshAbs: Widespread contamination of arsenic in Bangladesh has been jeopardizing the health of millions of people. Residents of Matlab, Bangladesh, are among the millions at risk. Using bivariate models in the analysis of survey data, knowledge of health risks and avoidance of arsenic exposure in response to widespread contamination of arsenic for residents of Matlab were estimated. The models examined individuals' knowledge of an arsenic problem in the household and knowledge of specific illnesses caused by arsenic exposure. The likelihood of avoiding exposure to arsenic contamination was further examined. Results of the estimation showed that individual's knowledge of arsenic problems in the household was gathered through awareness campaigns and by word of mouth and that knowledge of illnesses was predicated on education, health, presence of children, elderly and young women. Adoption of avoidance measures was not affected by exposure to arsenic-information sources, but level of education had a statistically significant positive effect on the decision to avoid arsenic exposure. Lack of convenience of safe drinking-water practices lead people to persist in drinking arsenic-contaminated water."
226,Bandara et al. 2008,Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (Tilapia)," Chronic renal failure (CRF), in the main agricultural region under reservoir based cascade irrigation in Sri Lanka has reached crisis proportion. Over 5,000 patients in the region are under treatment for CRF. The objective of this study is to establish the etiology of the CRF. Concentrations of nine heavy metals were determined in sediments, soils of reservoir peripheries, water and Nelumbo nucifera (lotus) grown in five major reservoirs that supply irrigation water. All five reservoirs carried higher levels of dissolved cadmium (Cd), iron (Fe) and lead (Pb). Dissolved Cd in reservoir water ranged from 0.03 to 0.06 mg/l. Sediment Cd concentration was 1.78-2.45 mg/kg. No arsenic (As) was detected. Cd content in lotus rhizomes was 253.82 mg/kg. The Provisional Tolerable Weekly Intake (PTWI) of Cd based on extreme exposure of rice is 8.702-15.927 mu g/kg body weight (BW) for different age groups, 5-50 years. The PTWI of Cd due to extreme exposure of fish is 6.773-12.469 mu g/kg BW. The PTWI on a rice staple with fish is 15.475-28.396 mu g/kg BW. The mean urinary cadmium (UCd) concentration in CRF patients of age group 40-60 years was 7.58 mu g Cd/g creatinine and in asymptomatic persons UCd was 11.62 mu g Cd/g creatinine, indicating a chronic exposure to Cd. The possible source of Cd in reservoir sediments and water is Cd-contaminated agrochemicals. The CRF prevalent in north central Sri Lanka is a result of chronic dietary intake of Cd, supported by high natural levels of fluoride in drinking water, coupled with neglecting of routine de-silting of reservoirs for the past 20 years.","Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (Tilapia)Abs: Chronic renal failure (CRF), in the main agricultural region under reservoir based cascade irrigation in Sri Lanka has reached crisis proportion. Over 5,000 patients in the region are under treatment for CRF. The objective of this study is to establish the etiology of the CRF. Concentrations of nine heavy metals were determined in sediments, soils of reservoir peripheries, water and Nelumbo nucifera (lotus) grown in five major reservoirs that supply irrigation water. All five reservoirs carried higher levels of dissolved cadmium (Cd), iron (Fe) and lead (Pb). Dissolved Cd in reservoir water ranged from 0.03 to 0.06 mg/l. Sediment Cd concentration was 1.78-2.45 mg/kg. No arsenic (As) was detected. Cd content in lotus rhizomes was 253.82 mg/kg. The Provisional Tolerable Weekly Intake (PTWI) of Cd based on extreme exposure of rice is 8.702-15.927 mu g/kg body weight (BW) for different age groups, 5-50 years. The PTWI of Cd due to extreme exposure of fish is 6.773-12.469 mu g/kg BW. The PTWI on a rice staple with fish is 15.475-28.396 mu g/kg BW. The mean urinary cadmium (UCd) concentration in CRF patients of age group 40-60 years was 7.58 mu g Cd/g creatinine and in asymptomatic persons UCd was 11.62 mu g Cd/g creatinine, indicating a chronic exposure to Cd. The possible source of Cd in reservoir sediments and water is Cd-contaminated agrochemicals. The CRF prevalent in north central Sri Lanka is a result of chronic dietary intake of Cd, supported by high natural levels of fluoride in drinking water, coupled with neglecting of routine de-silting of reservoirs for the past 20 years."
227,Barber et al. 2009,"A Dietary Risk Assessment for Indigenous Consumption of Natural Salt Deposits in the Darhad Valley, Northern Mongolia"," The nomadic herding population of the Darhad Valley, in northern Mongolia, collects and utilizes a salt precipitate, called hujir, which develops at the saline system, Tohi. This culturally important indigenous dietary supplement is consumed daily as an ingredient in a salty milk-tea and because of its essential micro- and macronutrients it is a beneficial and necessary part of their daily diet. Despite its benefits, there are increasing health concerns among the Darhad people as a result of consuming hujir. Therefore, we conducted a dietary risk assessment. Consumption rates were obtained from interviews with nomadic herders of the valley and a chronic exposure assessment was completed using chemical analyses on hujir samples. A combination of chronic toxicity threshold values, dietary reference intake recommendations, and drinking water guidelines were used to estimate dietary risks related to hujir consumption. Exposures to arsenic, fluoride, and nitrate were as high as 33, 1.2, and 1.3 times the chronic oral reference dose, respectively. Exposures to antimony, arsenic, and lead were 1.7, 19, and 14 times the drinking water guidelines, respectively. Given these results, additional studies are needed to better understand possible health effects associated with hujir consumption in the Darhad population, especially for arsenic.","A Dietary Risk Assessment for Indigenous Consumption of Natural Salt Deposits in the Darhad Valley, Northern MongoliaAbs: The nomadic herding population of the Darhad Valley, in northern Mongolia, collects and utilizes a salt precipitate, called hujir, which develops at the saline system, Tohi. This culturally important indigenous dietary supplement is consumed daily as an ingredient in a salty milk-tea and because of its essential micro- and macronutrients it is a beneficial and necessary part of their daily diet. Despite its benefits, there are increasing health concerns among the Darhad people as a result of consuming hujir. Therefore, we conducted a dietary risk assessment. Consumption rates were obtained from interviews with nomadic herders of the valley and a chronic exposure assessment was completed using chemical analyses on hujir samples. A combination of chronic toxicity threshold values, dietary reference intake recommendations, and drinking water guidelines were used to estimate dietary risks related to hujir consumption. Exposures to arsenic, fluoride, and nitrate were as high as 33, 1.2, and 1.3 times the chronic oral reference dose, respectively. Exposures to antimony, arsenic, and lead were 1.7, 19, and 14 times the drinking water guidelines, respectively. Given these results, additional studies are needed to better understand possible health effects associated with hujir consumption in the Darhad population, especially for arsenic."
228,Binks et al. 2005,Mortality experience of male workers at a UK tin smelter," Background Between 1937 and 1991, Capper Pass and Sons Limited operated a tin smelter complex in North Humberside, UK, at which employees were potentially exposed to a number of substances, including lead, arsenic, cadmium and natural series radionuclides. Decommissioning and site clearance continued until 1995. Between 1967 and 1995 the company was a subsidiary of Rio Tinto plc. Aims The aim was to identify any significant excess, or deficits, in mortality among former employees that might be attributable to factors associated with occupation. Methods We defined a cohort of 1462 males who had been employed for at least 12 months between 1/11/1967 and 28/7/1995, followed-up through to 31/12/2001. The mortality of the cohort was compared against that expected for both national and regional populations. Results Mortality from all causes and all cancers did not differ from that expected. Mortality from ischaemic heart disease showed a deficit and mortality from lung cancer showed a statistically significant excess. Mortality from smoking related diseases other than lung cancer showed a non-significant deficit. Conclusions The pattern of lung cancer mortality is consistent with the hypothesis that the risk of lung cancer has been enhanced by occupational exposure to one or more carcinogens, the effect of which diminishes with time since exposure. The deficit in ischaemic heart disease may be attributed to a protective effect from manual labour. The results provide no evidence for attribution of other excess or deficits in mortality to factors associated with employment.","Mortality experience of male workers at a UK tin smelterAbs: Background Between 1937 and 1991, Capper Pass and Sons Limited operated a tin smelter complex in North Humberside, UK, at which employees were potentially exposed to a number of substances, including lead, arsenic, cadmium and natural series radionuclides. Decommissioning and site clearance continued until 1995. Between 1967 and 1995 the company was a subsidiary of Rio Tinto plc. Aims The aim was to identify any significant excess, or deficits, in mortality among former employees that might be attributable to factors associated with occupation. Methods We defined a cohort of 1462 males who had been employed for at least 12 months between 1/11/1967 and 28/7/1995, followed-up through to 31/12/2001. The mortality of the cohort was compared against that expected for both national and regional populations. Results Mortality from all causes and all cancers did not differ from that expected. Mortality from ischaemic heart disease showed a deficit and mortality from lung cancer showed a statistically significant excess. Mortality from smoking related diseases other than lung cancer showed a non-significant deficit. Conclusions The pattern of lung cancer mortality is consistent with the hypothesis that the risk of lung cancer has been enhanced by occupational exposure to one or more carcinogens, the effect of which diminishes with time since exposure. The deficit in ischaemic heart disease may be attributed to a protective effect from manual labour. The results provide no evidence for attribution of other excess or deficits in mortality to factors associated with employment."
229,Bocio et al. 2005,"Human exposure to metals through the diet in Tarragona, Spain - Temporal trend"," The concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (TI), and vanadium (V) were determined in a number of food items purchased in zones of Tarragona County (Catalonia, Spain) near a hazardous waste incinerator (HWI), which has been operating since 1999. Food samples corresponded to the following groups: meat, fish and seafood, pulses, cereals, vegetables, fruits, tubers, whole milk, yogurt, eggs, and sugar. Be and TI were under their respective limits of detection in all samples. For,the analyzed trace elements, the dietary intake by the general population of Tarragona was 458.5 mu g/d for As, 14.3 mu g/d for Cd, 88.3 mu g/d for Cr, 5.3 mu g/d for Hg, 2421.4 mu g/d for Mn, 138.3 mu g/d for Ni, 44.8 mu g/d for Pb, 34.6 mu g/d for Sn, and 28.9 mu g/d for V. Results were compared with those found in a baseline survey carried out in the same area during the construction of the HWI (1996-1998). In general terms, the dietary intake of metals in 2003 was comparatively similar to those found in the baseline survey. For the most toxic elements (As, Cd, Hg, and Pb), it was under their respective Provisional Tolerable Weekly Intake (PTWI) established by the FAC/WHO.","Human exposure to metals through the diet in Tarragona, Spain - Temporal trendAbs: The concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (TI), and vanadium (V) were determined in a number of food items purchased in zones of Tarragona County (Catalonia, Spain) near a hazardous waste incinerator (HWI), which has been operating since 1999. Food samples corresponded to the following groups: meat, fish and seafood, pulses, cereals, vegetables, fruits, tubers, whole milk, yogurt, eggs, and sugar. Be and TI were under their respective limits of detection in all samples. For,the analyzed trace elements, the dietary intake by the general population of Tarragona was 458.5 mu g/d for As, 14.3 mu g/d for Cd, 88.3 mu g/d for Cr, 5.3 mu g/d for Hg, 2421.4 mu g/d for Mn, 138.3 mu g/d for Ni, 44.8 mu g/d for Pb, 34.6 mu g/d for Sn, and 28.9 mu g/d for V. Results were compared with those found in a baseline survey carried out in the same area during the construction of the HWI (1996-1998). In general terms, the dietary intake of metals in 2003 was comparatively similar to those found in the baseline survey. For the most toxic elements (As, Cd, Hg, and Pb), it was under their respective Provisional Tolerable Weekly Intake (PTWI) established by the FAC/WHO."
230,Carmines et al. 2005,Toxicologic evaluation of licorice extract as a cigarette ingredient," Licorice extract (block, powder or liquid) may be applied to cigarette tobacco at levels of about 1-4% to enhance and harmonize the flavor characteristics of smoke, improve moisture holding characteristics of tobacco, and act as a surface active agent for ingredient application. Neat material pyrolysis studies, and smoke chemistry and biological activity studies (bacterial mutagenicity, cytotoxicity, micronucleus, and sub-chronic inhalation) with mainstream smoke, or mainstream smoke preparations from cigarettes containing various target levels (1.5-12%) of the licorice extracts were performed to provide data for an assessment of the use of licorice extract as a cigarette tobacco ingredient. At simulated tobacco burning temperatures up to 900 degrees C all forms of neat licorice extract pyrolyzed extensively, yielding small amounts of benzene, toluene, phenol and acetaldehyde with no indication that licorice extracts would transfer intact to mainstream smoke. As a single ingredient added to cigarette tobacco, block licorice extract at a target level of 12.5% increased smoke constituents including selected PAH, arsenic, lead, phenol and formaldehyde (on a TPM basis), while licorice extract powder (target level of 8% tobacco) increased select PAH, phenol and formaldehyde (on a TPM basis). Lower target application levels (including typical application levels) of block, powder or liquid licorice extract did not significantly alter the smoke chemistry profile. Biological tests indicated no relevant difference in the genotoxic or cytotoxic potential of either mainstream smoke (or smoke preparations) from cigarettes with added licorice extracts compared to control cigarettes. In subchronic 90-day rat inhalation studies, the mainstream smoke from cigarettes with 12.5% added block and 8% added powder licorice extract contained higher formaldehyde concentrations compared to control cigarette smoke. Female rats in the 12.5% block licorice extract exposure group displayed an increased incidence and severity of epithelial hyperplasia in the nose (level 2), with no relevant respiratory tract changes in the 8% powder licorice extract exposed rats. At the lower licorice extract application levels (1.25-5%), there was no indication of increased formaldehyde concentration in the smoke atmosphere and no relevant changes in respiratory tract tissues. Mineralcorticoid-like effects which have been associated with excess licorice ingestion were not found in any of the smoke inhalation studies. The results of these studies with various forms of licorice extract applied to cigarette tobacco suggest that licorice extract to cigarette tobacco at levels of <= 5% does not discernibly alter the smoke chemistry or biological effects normally associated with mainstream cigarette smoke. (c) 2005 Published by Elsevier Ltd.","Toxicologic evaluation of licorice extract as a cigarette ingredientAbs: Licorice extract (block, powder or liquid) may be applied to cigarette tobacco at levels of about 1-4% to enhance and harmonize the flavor characteristics of smoke, improve moisture holding characteristics of tobacco, and act as a surface active agent for ingredient application. Neat material pyrolysis studies, and smoke chemistry and biological activity studies (bacterial mutagenicity, cytotoxicity, micronucleus, and sub-chronic inhalation) with mainstream smoke, or mainstream smoke preparations from cigarettes containing various target levels (1.5-12%) of the licorice extracts were performed to provide data for an assessment of the use of licorice extract as a cigarette tobacco ingredient. At simulated tobacco burning temperatures up to 900 degrees C all forms of neat licorice extract pyrolyzed extensively, yielding small amounts of benzene, toluene, phenol and acetaldehyde with no indication that licorice extracts would transfer intact to mainstream smoke. As a single ingredient added to cigarette tobacco, block licorice extract at a target level of 12.5% increased smoke constituents including selected PAH, arsenic, lead, phenol and formaldehyde (on a TPM basis), while licorice extract powder (target level of 8% tobacco) increased select PAH, phenol and formaldehyde (on a TPM basis). Lower target application levels (including typical application levels) of block, powder or liquid licorice extract did not significantly alter the smoke chemistry profile. Biological tests indicated no relevant difference in the genotoxic or cytotoxic potential of either mainstream smoke (or smoke preparations) from cigarettes with added licorice extracts compared to control cigarettes. In subchronic 90-day rat inhalation studies, the mainstream smoke from cigarettes with 12.5% added block and 8% added powder licorice extract contained higher formaldehyde concentrations compared to control cigarette smoke. Female rats in the 12.5% block licorice extract exposure group displayed an increased incidence and severity of epithelial hyperplasia in the nose (level 2), with no relevant respiratory tract changes in the 8% powder licorice extract exposed rats. At the lower licorice extract application levels (1.25-5%), there was no indication of increased formaldehyde concentration in the smoke atmosphere and no relevant changes in respiratory tract tissues. Mineralcorticoid-like effects which have been associated with excess licorice ingestion were not found in any of the smoke inhalation studies. The results of these studies with various forms of licorice extract applied to cigarette tobacco suggest that licorice extract to cigarette tobacco at levels of <= 5% does not discernibly alter the smoke chemistry or biological effects normally associated with mainstream cigarette smoke. (c) 2005 Published by Elsevier Ltd."
231,Chang et al. 2005,"Impaction collection and slurry sampling for the determination of arsenic, cadmium, and lead in sidestream cigarette smoke by inductively coupled plasma-mass spectrometry"," The slurry sampling technique has been applied for the determination of arsenic, cadmium and lead in sidestream cigarette smoke condensate ( SS CSC) by inductively coupled plasma mass spectrometry ( ICPMS). The smoke collection system consists of a ""fishtail"" chimney in conjunction with an impaction trap and a mixed cellulose ester ( MCE) backup filter for the SS CSC collection. The smoke condensates, collected at three different regions of the system ( i.e. the inner wall of the chimney, the impaction trap and the MCE filter), were individually prepared and analyzed and showed that about 70 and 20% of Cd and Pb, respectively, were trapped by the impaction trap and the MCE filter with less than 5% trapped by the chimney. In contrast, about 60% of As was trapped by the impactor and a relatively high percentage of As, about 30%, was deposited onto the inner wall of the chimney. The uneven distribution of trace metals at each collection stage strongly suggested that the composition of smoke aerosol and the associated physical form of the analytes may be different. The yields of As, Cd and Pb for the sidestream cigarette smoke of the 1R4F reference cigarette were 29.5 +/- 2.4, 421 +/- 6.6 and 46.4 +/- 0.9 ng cigarette(-1) ( n = 3) respectively, when the cigarette was smoked according to the smoking regime: 45 mL puff volume of 2-s puff duration at an interval of 30 s with 50% ventilation holes covered. The analytical results for the slurry sampling technique were also compared with other sample preparation techniques and show good agreement.","Impaction collection and slurry sampling for the determination of arsenic, cadmium, and lead in sidestream cigarette smoke by inductively coupled plasma-mass spectrometryAbs: The slurry sampling technique has been applied for the determination of arsenic, cadmium and lead in sidestream cigarette smoke condensate ( SS CSC) by inductively coupled plasma mass spectrometry ( ICPMS). The smoke collection system consists of a ""fishtail"" chimney in conjunction with an impaction trap and a mixed cellulose ester ( MCE) backup filter for the SS CSC collection. The smoke condensates, collected at three different regions of the system ( i.e. the inner wall of the chimney, the impaction trap and the MCE filter), were individually prepared and analyzed and showed that about 70 and 20% of Cd and Pb, respectively, were trapped by the impaction trap and the MCE filter with less than 5% trapped by the chimney. In contrast, about 60% of As was trapped by the impactor and a relatively high percentage of As, about 30%, was deposited onto the inner wall of the chimney. The uneven distribution of trace metals at each collection stage strongly suggested that the composition of smoke aerosol and the associated physical form of the analytes may be different. The yields of As, Cd and Pb for the sidestream cigarette smoke of the 1R4F reference cigarette were 29.5 +/- 2.4, 421 +/- 6.6 and 46.4 +/- 0.9 ng cigarette(-1) ( n = 3) respectively, when the cigarette was smoked according to the smoking regime: 45 mL puff volume of 2-s puff duration at an interval of 30 s with 50% ventilation holes covered. The analytical results for the slurry sampling technique were also compared with other sample preparation techniques and show good agreement."
232,Cleland et al. 2009,"Arsenic Exposure within the Korean Community (United States) Based on Dietary Behavior and Arsenic Levels in Hair, Urine, Air, and Water"," BACKGROUND: Determining arsenic exposure in groups based on geographic location, dietary behaviors, or lifestyles is important, as even moderate exposures may lead to health concerns. OBJECTIVES/METHODS: The Korean community in Washington State, represents a group warranting investigation, as they consume foods (e.g., shellfish, rice, finfish, and seaweed) known to contain arsenic. As part of the Arsenic Mercury Intake Biometric Study, we examined the arsenic levels in hair and urine along with the diets of 108 women of childbearing age from within this community. Arsenic levels in indoor air and drinking water were also investigated, and shellfish commonly consumed were collected and analyzed for total and speciated arsenic. RESULTS: The six shellfish species analyzed (n = 667) contain total arsenic (range, 1-5 mu g/g) but are a small source of inorganic arsenic (range, 0.01-0.12 mu g/g). Six percent of the individuals may have elevated urinary inorganic arsenic levels (> 10 mu g/L) due to diet. Seaweed, rice, shellfish, and finfish are principal sources for total arsenic intake/excretion based on mass balance estimates. Rice consumption (163 g/person/day) may be a significant source of inorganic arsenic. Air and water are not significant sources of exposure. Hair is a poor biometric for examining arsenic levels at low to moderate exposures. CONCLUSIONS: We conclude that a portion of this community may have dietary inorganic arsenic exposure resulting in urine levels exceeding 10 mu g/L. Although their exposure is below that associated with populations exposed to high levels of arsenic from drinking water (> 100 mu g/L), their exposure may be among the highest in the United States.","Arsenic Exposure within the Korean Community (United States) Based on Dietary Behavior and Arsenic Levels in Hair, Urine, Air, and WaterAbs: BACKGROUND: Determining arsenic exposure in groups based on geographic location, dietary behaviors, or lifestyles is important, as even moderate exposures may lead to health concerns. OBJECTIVES/METHODS: The Korean community in Washington State, represents a group warranting investigation, as they consume foods (e.g., shellfish, rice, finfish, and seaweed) known to contain arsenic. As part of the Arsenic Mercury Intake Biometric Study, we examined the arsenic levels in hair and urine along with the diets of 108 women of childbearing age from within this community. Arsenic levels in indoor air and drinking water were also investigated, and shellfish commonly consumed were collected and analyzed for total and speciated arsenic. RESULTS: The six shellfish species analyzed (n = 667) contain total arsenic (range, 1-5 mu g/g) but are a small source of inorganic arsenic (range, 0.01-0.12 mu g/g). Six percent of the individuals may have elevated urinary inorganic arsenic levels (> 10 mu g/L) due to diet. Seaweed, rice, shellfish, and finfish are principal sources for total arsenic intake/excretion based on mass balance estimates. Rice consumption (163 g/person/day) may be a significant source of inorganic arsenic. Air and water are not significant sources of exposure. Hair is a poor biometric for examining arsenic levels at low to moderate exposures. CONCLUSIONS: We conclude that a portion of this community may have dietary inorganic arsenic exposure resulting in urine levels exceeding 10 mu g/L. Although their exposure is below that associated with populations exposed to high levels of arsenic from drinking water (> 100 mu g/L), their exposure may be among the highest in the United States."
233,De Chaudhuri et al. 2008,"Genetic variants associated with arsenic susceptibility: Study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genes"," BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP) arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08-2.66] for His20His; OR = 1.66 [95% Cl, 1.04-2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05-2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions.","Genetic variants associated with arsenic susceptibility: Study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genesAbs: BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP) arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08-2.66] for His20His; OR = 1.66 [95% Cl, 1.04-2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05-2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions."
234,de Figueiredo et al. 2007,Arsenic occurrence in Brazil and human exposure," Environmental exposure to arsenic (As) in terms of public health is receiving increasing attention worldwide following cases of mass contamination in different parts of the world. However, there is a scarcity of data available on As geochemistry in Brazilian territory, despite the known occurrence of As in some of the more severely polluted areas of Brazil. The purpose of this paper is to discuss existing data on As distribution in Brazil based on recent investigations in three contaminated areas as well as results from the literature. To date, integrated studies on environmental and anthropogenic sources of As contamination have been carried out only in three areas in Brazil: (1) the Southeastern region, known as the Iron Quadrangle, where As was released into the drainage systems, soils and atmosphere as a result of gold mining; (2) the Ribeira Valley, where As occurs in Pb-Zn mine wastes and naturally in As-rich rocks and soils; (3) the Amazon region, including the Santana area, where As is associated with manganese ores mined over the last 50 years. Toxicological studies revealed that the populations were not exposed to elevated levels of As, with the As concentrations in surface water in these areas rarely exceeding 10 mu g/L. Deep weathering of bedrocks along with formation of Fe/Al-enriched soils and sediments function as a chemical barrier that prevents the release of As into the water. In addition, the tropical climate results in high rates of precipitation in the northern and southeastern regions and, hence, the As contents of drinking water is diluted. Severe cases of human As exposure related to non-point pollution sources have not been reported in Brazil. However, increasing awareness of the adverse health effects of As will eventually lead to a more complete picture of the distribution of As in Brazil.","Arsenic occurrence in Brazil and human exposureAbs: Environmental exposure to arsenic (As) in terms of public health is receiving increasing attention worldwide following cases of mass contamination in different parts of the world. However, there is a scarcity of data available on As geochemistry in Brazilian territory, despite the known occurrence of As in some of the more severely polluted areas of Brazil. The purpose of this paper is to discuss existing data on As distribution in Brazil based on recent investigations in three contaminated areas as well as results from the literature. To date, integrated studies on environmental and anthropogenic sources of As contamination have been carried out only in three areas in Brazil: (1) the Southeastern region, known as the Iron Quadrangle, where As was released into the drainage systems, soils and atmosphere as a result of gold mining; (2) the Ribeira Valley, where As occurs in Pb-Zn mine wastes and naturally in As-rich rocks and soils; (3) the Amazon region, including the Santana area, where As is associated with manganese ores mined over the last 50 years. Toxicological studies revealed that the populations were not exposed to elevated levels of As, with the As concentrations in surface water in these areas rarely exceeding 10 mu g/L. Deep weathering of bedrocks along with formation of Fe/Al-enriched soils and sediments function as a chemical barrier that prevents the release of As into the water. In addition, the tropical climate results in high rates of precipitation in the northern and southeastern regions and, hence, the As contents of drinking water is diluted. Severe cases of human As exposure related to non-point pollution sources have not been reported in Brazil. However, increasing awareness of the adverse health effects of As will eventually lead to a more complete picture of the distribution of As in Brazil."
235,Dhar et al. 2007,Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period," The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0 mg/kg body weight (bw) to groups II, III and IV (n = 6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1 M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 mu m), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be the underlying basis for some of the functional deficits encountered in the later period of life. (C) 2007 Elsevier Ireland Ltd. All rights reserved.","Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) periodAbs: The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0 mg/kg body weight (bw) to groups II, III and IV (n = 6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1 M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 mu m), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be the underlying basis for some of the functional deficits encountered in the later period of life. (C) 2007 Elsevier Ireland Ltd. All rights reserved."
236,Donadini et al. 2008,"Arsenic, Cadmium and Lead in Beers from the Italian Market"," Nineteen beer brands from the Italian market were surveyed for the presence of arsenic, cadmium and lead in January of 2007. Detection was performed by means of inductively coupled plasma-mass spectrometry (ICP-MS). Average arsenic content was 10.82 +/- 5.54 mu g/L, while cadmium (0.16 +/- 0.15 mu g/L) and lead (1.84 +/- 3.24 mu g/L) were significantly lower (P<0.05). Overall, this survey indicated that beer may contribute heavy metals to the diet. Nevertheless, the dietary exposure to these contaminants is unlikely to constitute a hazard to the consumer's health due to the low level of contamination found and to the low annual per capita consumption of beer in Italy.","Arsenic, Cadmium and Lead in Beers from the Italian MarketAbs: Nineteen beer brands from the Italian market were surveyed for the presence of arsenic, cadmium and lead in January of 2007. Detection was performed by means of inductively coupled plasma-mass spectrometry (ICP-MS). Average arsenic content was 10.82 +/- 5.54 mu g/L, while cadmium (0.16 +/- 0.15 mu g/L) and lead (1.84 +/- 3.24 mu g/L) were significantly lower (P<0.05). Overall, this survey indicated that beer may contribute heavy metals to the diet. Nevertheless, the dietary exposure to these contaminants is unlikely to constitute a hazard to the consumer's health due to the low level of contamination found and to the low annual per capita consumption of beer in Italy."
237,Feng et al. 2009,Chemical speciation of fine particle bound trace metals," This study reported quantifications of fine particle bound trace metals and their potential health risks for residents in Guangzhou, a rapidly developing and most populated city in South China. The fine particle samples were collected from October 29(th). to November 8(th). of 2006 at two different elevations in a mainly residential area and analyzed for the total concentration of aluminum, iron, zinc, lead, manganese, copper, arsenic, chromium, nickel, cadmium, molybdenum and cobalt. Results showed that the fine particle concentrations ranged from 95.8 mu g/m(3) to 194.7 mu g/m(3) at the ground and 83.3-190.0 mu g/m(3) on the roof, which were much higher than the 24 h fine particle standard (35 mu g/m(3)) recommended by USEPA. The total concentrations of zinc, lead, arsenic, chromium and cadmium in fine particle were 504.8, 201.6, 24.3, 7.7 and 4.4 ng/m(3), respectively, which were comparable to other major cities of China, but much higher than major cities outside of China. A sequential extraction procedure was used to fractionate these fine particle bound metals into four different fractions. Results indicated that most toxic metals were mainly distributed in bioavailable fractions. For instance, about 91% of cadmium, 85% of lead and 74% of arsenic were in bioavailable forms. Risk calculations with a simple exposure assessment model showed that the cancer risks of the bioavailable fractions of arsenic, chromium and cadmium were 3 to 33 times greater than usual goal, indicating serious health risks to the residents in this urban area.","Chemical speciation of fine particle bound trace metalsAbs: This study reported quantifications of fine particle bound trace metals and their potential health risks for residents in Guangzhou, a rapidly developing and most populated city in South China. The fine particle samples were collected from October 29(th). to November 8(th). of 2006 at two different elevations in a mainly residential area and analyzed for the total concentration of aluminum, iron, zinc, lead, manganese, copper, arsenic, chromium, nickel, cadmium, molybdenum and cobalt. Results showed that the fine particle concentrations ranged from 95.8 mu g/m(3) to 194.7 mu g/m(3) at the ground and 83.3-190.0 mu g/m(3) on the roof, which were much higher than the 24 h fine particle standard (35 mu g/m(3)) recommended by USEPA. The total concentrations of zinc, lead, arsenic, chromium and cadmium in fine particle were 504.8, 201.6, 24.3, 7.7 and 4.4 ng/m(3), respectively, which were comparable to other major cities of China, but much higher than major cities outside of China. A sequential extraction procedure was used to fractionate these fine particle bound metals into four different fractions. Results indicated that most toxic metals were mainly distributed in bioavailable fractions. For instance, about 91% of cadmium, 85% of lead and 74% of arsenic were in bioavailable forms. Risk calculations with a simple exposure assessment model showed that the cancer risks of the bioavailable fractions of arsenic, chromium and cadmium were 3 to 33 times greater than usual goal, indicating serious health risks to the residents in this urban area."
238,Flora et al. 2009,"Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brain"," We studied the effects of combined exposure to arsenic and fluoride on (i) brain biogenic amines, oxidative stress and its correlation with glutathione and linked enzymes; (ii) alterations in the structural integrity of DNA; and (iii) brain and blood arsenic and fluoride levels. Efficacy of alpha-tocopherol in reducing these changes was also determined. Male mice were exposed to sodium meta arsenite (50 ppm) and sodium fluoride (50 ppm) individually and in combination for ten weeks. Animals were given vitamin E supplementation (5 mg/kg, i.m., alternate days) throughout the experiment. Exposure to arsenic and fluoride significantly decreased the levels of brain biogenic amines. However; acetyl cholinesterase (AChE) and monoamine oxidase (MAO) activities showed an increase on fluoride exposure. There was also an increase in reactive oxygen species, thiobarbituric acid reactive species level, glutathione S-transferase and glutathione peroxidase activities and decreased superoxide dismutase activity, GSH:GSSG ratio, glucose 6-phosphate dehydrogenase activity. Combined exposure to these toxicants produced more pronounced effects on AChE, MAO, SOD and catalase activities. Infrared spectra showed less toxicity during combined exposure as the characteristic peaks of cytosine and alpha-helical structure of DNA were observed in normal and arsenic plus fluoride-exposed animals. Vitamin E reduced brain fluoride level and tissue oxidative stress but had no effect on arsenic. Combined exposure to arsenic and fluoride does not necessarily lead to more pronounced toxicity and interestingly exhibit some antagonistic effects. Vitamin E supplementation may be of added value in reverting some of the toxic effects. (c) 2009 Elsevier B.V. All rights reserved.","Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brainAbs: We studied the effects of combined exposure to arsenic and fluoride on (i) brain biogenic amines, oxidative stress and its correlation with glutathione and linked enzymes; (ii) alterations in the structural integrity of DNA; and (iii) brain and blood arsenic and fluoride levels. Efficacy of alpha-tocopherol in reducing these changes was also determined. Male mice were exposed to sodium meta arsenite (50 ppm) and sodium fluoride (50 ppm) individually and in combination for ten weeks. Animals were given vitamin E supplementation (5 mg/kg, i.m., alternate days) throughout the experiment. Exposure to arsenic and fluoride significantly decreased the levels of brain biogenic amines. However; acetyl cholinesterase (AChE) and monoamine oxidase (MAO) activities showed an increase on fluoride exposure. There was also an increase in reactive oxygen species, thiobarbituric acid reactive species level, glutathione S-transferase and glutathione peroxidase activities and decreased superoxide dismutase activity, GSH:GSSG ratio, glucose 6-phosphate dehydrogenase activity. Combined exposure to these toxicants produced more pronounced effects on AChE, MAO, SOD and catalase activities. Infrared spectra showed less toxicity during combined exposure as the characteristic peaks of cytosine and alpha-helical structure of DNA were observed in normal and arsenic plus fluoride-exposed animals. Vitamin E reduced brain fluoride level and tissue oxidative stress but had no effect on arsenic. Combined exposure to arsenic and fluoride does not necessarily lead to more pronounced toxicity and interestingly exhibit some antagonistic effects. Vitamin E supplementation may be of added value in reverting some of the toxic effects. (c) 2009 Elsevier B.V. All rights reserved."
239,Fowler et al. 2008,Proteomic and metabolomic biomarkers for assessing low dose toxic trace element interactions: An overview," Humans are exposed to a number of toxic and essential trace elements from air, food, and water (Nordberg et al. 2007a) and there are major riskassessment issues concerning to what extent these metallic mixture exposures produce toxic or beneficial public health outcomes. During recent decades, there has been growing interest in the development of sensitive, specific and rapid biological tests (biomarkers) capable of providing objective quantifiable data regarding cellular responses to low-dose trace element exposures either alone or as mixtures (Fowler 2005). In more recent years, the “omic” biomarkers (genomic, proteomic, and metabolomic) have been a major focus of biomarker development. This brief overview will focus on how metabolomic and proteomic biomarkers have provided useful quantifiable data of great value for interpreting the biological consequences of single or combined exposures to lead, cadmium, arsenic and the binary III–V semiconductors gallium arsenide and indium arsenide. Biomarker data will be correlated where possible with other quantitative morphological data and clinical outcomes. It is worth noting that “omic” biomarkers will undoubtedly become of even greater importance for trace element riskassessment purposes since all of the metals/metalloids, as well as others, are being utilized in the production of nanomaterials which will increase the probability of human exposures.","Proteomic and metabolomic biomarkers for assessing low dose toxic trace element interactions: An overviewAbs: Humans are exposed to a number of toxic and essential trace elements from air, food, and water (Nordberg et al. 2007a) and there are major riskassessment issues concerning to what extent these metallic mixture exposures produce toxic or beneficial public health outcomes. During recent decades, there has been growing interest in the development of sensitive, specific and rapid biological tests (biomarkers) capable of providing objective quantifiable data regarding cellular responses to low-dose trace element exposures either alone or as mixtures (Fowler 2005). In more recent years, the “omic” biomarkers (genomic, proteomic, and metabolomic) have been a major focus of biomarker development. This brief overview will focus on how metabolomic and proteomic biomarkers have provided useful quantifiable data of great value for interpreting the biological consequences of single or combined exposures to lead, cadmium, arsenic and the binary III–V semiconductors gallium arsenide and indium arsenide. Biomarker data will be correlated where possible with other quantitative morphological data and clinical outcomes. It is worth noting that “omic” biomarkers will undoubtedly become of even greater importance for trace element riskassessment purposes since all of the metals/metalloids, as well as others, are being utilized in the production of nanomaterials which will increase the probability of human exposures."
240,Guo et al. 2006,Levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia," The most common health effects from drinking-water containing dissolved arsenic are skin abnormalities and lesions that are typically diagnosed as keratosis and pigment disorder. It was previously reported that the prevalence of cutaneous lesions was about 44% in arsenic-affected villages. However, there has been little research on the relationship between levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia. One study examined the association between the prevalence of keratosis and levels of arsenic exposure and the relationship between pigment disorder and levels of arsenic exposure among villagers aged 18 years or older in the arsenic-affected village of Hetao Plain in Inner Mongolia, PR China. The study included 227 participants who were affected by cutaneous lesions and 221 participants who were not affected by cutaneous lesions diagnosed in 1996 and 1998. Well-water drunk by the participants was collected to analyze arsenic content. Adjusting for age, sex, and smoking, logistic regression was applied to calculate the risks that arsenic in drinking-water will lead to cutaneous lesions. The results from the logistic regression showed that, with the increase of arsenic concentration in water, the risk of pigment disorder also increased (odds ratio [OR]=5.25, 95% confidence interval [CI] 1.32-83.24 for 50-199 mu g/L; OR=10.97, 95% CI 1.50-79.95 for 200-499 mu g/L; OR=10.00, 95% CI 1.39-71.77 for >= 500 mu g/L (p=0.000), but the association between risk of keratosis and levels of arsenic was not significant (p=0.346). The findings suggest that keratosis is an early feature of arsenic poisoning, and the development of pigment disorder depends on higher doses of arsenic intake rather than keratosis. Further studies are needed to confirm that cutaneous lesions and other adverse health effects occur at low levels of arsenic exposure.","Levels of arsenic in drinking-water and cutaneous lesions in Inner MongoliaAbs: The most common health effects from drinking-water containing dissolved arsenic are skin abnormalities and lesions that are typically diagnosed as keratosis and pigment disorder. It was previously reported that the prevalence of cutaneous lesions was about 44% in arsenic-affected villages. However, there has been little research on the relationship between levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia. One study examined the association between the prevalence of keratosis and levels of arsenic exposure and the relationship between pigment disorder and levels of arsenic exposure among villagers aged 18 years or older in the arsenic-affected village of Hetao Plain in Inner Mongolia, PR China. The study included 227 participants who were affected by cutaneous lesions and 221 participants who were not affected by cutaneous lesions diagnosed in 1996 and 1998. Well-water drunk by the participants was collected to analyze arsenic content. Adjusting for age, sex, and smoking, logistic regression was applied to calculate the risks that arsenic in drinking-water will lead to cutaneous lesions. The results from the logistic regression showed that, with the increase of arsenic concentration in water, the risk of pigment disorder also increased (odds ratio [OR]=5.25, 95% confidence interval [CI] 1.32-83.24 for 50-199 mu g/L; OR=10.97, 95% CI 1.50-79.95 for 200-499 mu g/L; OR=10.00, 95% CI 1.39-71.77 for >= 500 mu g/L (p=0.000), but the association between risk of keratosis and levels of arsenic was not significant (p=0.346). The findings suggest that keratosis is an early feature of arsenic poisoning, and the development of pigment disorder depends on higher doses of arsenic intake rather than keratosis. Further studies are needed to confirm that cutaneous lesions and other adverse health effects occur at low levels of arsenic exposure."
241,Halatek et al. 2009,"Association between occupational exposure to arsenic and neurological, respiratory and renal effects"," Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n=16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and beta(2)-microglobulin (beta M-2) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m(3)). The contents of lead did not exceed the TLV (0.05 mg/m(3)). Low CC16 levels in serum (12.1 mu g/l) of workers with SNS and VEP symptoms and highest level As-U (x(a) 39.0 mu g/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum beta M-2 and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system. (C) 2009 Elsevier Inc. All rights reserved.","Association between occupational exposure to arsenic and neurological, respiratory and renal effectsAbs: Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n=16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and beta(2)-microglobulin (beta M-2) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m(3)). The contents of lead did not exceed the TLV (0.05 mg/m(3)). Low CC16 levels in serum (12.1 mu g/l) of workers with SNS and VEP symptoms and highest level As-U (x(a) 39.0 mu g/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum beta M-2 and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system. (C) 2009 Elsevier Inc. All rights reserved."
242,Hassan 2005,Arsenic poisoning in Bangladesh: spatial mitigation planning with GIS and public participation," A PPGIS (Public Participatory Geographical Information System) has recently been developed in combination with PRA (Participatory Rural Appraisal) and GIs (Geographical Information Systems) methodologies to milise GIs in the context of the needs of communities that are involved with, and affected by development programmes. The impact of arsenic poisoning in Bangladesh is 'tragic and painful' on patients' health and their social life what was described as the 'worse mass poisoning in human history' in a WHO report. Deep tubewell is said to be a source of arsenic-free safe drinking water and people are mainly interested in deep tubewell water rather than rainwater harvesting, dug-wells, and pond-sand-filters (PSF) approved by the BAMWSP (Bangladesh Arsenic Mitigation Water Supply Project). This paper mainly explores the application and suitability of GIs with local community participation in deep tubewell planning for arsenic mitigation. The relevant data for this study were collected from the field survey. The PRA methods were used to obtain social and resource information; while a GIs was used to organise, analyse, and display the information. Participants from three different focus-groups were asked to determine their 'own priorities' for spatial planning of deep tubewell for arsenic-free water. The study results valuable community perspectives on deep tubewell planning and reveals the suitability of PPGIS in spatial planning for arsenic mitigation with local community mapping overlay. The process of dialogue and preparation of mental mapping within each focus-group participants lead to enhance information about community needs of deep tubewell in the study area. (c) 2005 Elsevier Ireland Ltd. All rights reserved.","Arsenic poisoning in Bangladesh: spatial mitigation planning with GIS and public participationAbs: A PPGIS (Public Participatory Geographical Information System) has recently been developed in combination with PRA (Participatory Rural Appraisal) and GIs (Geographical Information Systems) methodologies to milise GIs in the context of the needs of communities that are involved with, and affected by development programmes. The impact of arsenic poisoning in Bangladesh is 'tragic and painful' on patients' health and their social life what was described as the 'worse mass poisoning in human history' in a WHO report. Deep tubewell is said to be a source of arsenic-free safe drinking water and people are mainly interested in deep tubewell water rather than rainwater harvesting, dug-wells, and pond-sand-filters (PSF) approved by the BAMWSP (Bangladesh Arsenic Mitigation Water Supply Project). This paper mainly explores the application and suitability of GIs with local community participation in deep tubewell planning for arsenic mitigation. The relevant data for this study were collected from the field survey. The PRA methods were used to obtain social and resource information; while a GIs was used to organise, analyse, and display the information. Participants from three different focus-groups were asked to determine their 'own priorities' for spatial planning of deep tubewell for arsenic-free water. The study results valuable community perspectives on deep tubewell planning and reveals the suitability of PPGIS in spatial planning for arsenic mitigation with local community mapping overlay. The process of dialogue and preparation of mental mapping within each focus-group participants lead to enhance information about community needs of deep tubewell in the study area. (c) 2005 Elsevier Ireland Ltd. All rights reserved."
243,Howard et al. 2006,Risk assessment of arsenic mitigation options in Bangladesh," The provision of alternative water sources is the principal arsenic mitigation strategy in Bangladesh, but can lead to risk substitution. A study of arsenic mitigation options was undertaken to assess water quality and sanitary condition and to estimate the burden of disease associated with each technology in disability-adjusted life years (DALYs). Dugwells and pond-sand filters showed heavy microbial contamination in both dry and monsoon seasons, and the estimated burden of disease was high. Rainwater was of good quality in the monsoon but deteriorated in the dry season. Deep tubewells showed microbial contamination in the monsoon but not in the dry season and was the only technology to approach the World Health Organization's reference level of risk of 10(-6) DALYs. A few dugwells and one pond-sand filter showed arsenic in excess of 50 mu g/L. The findings suggest that deep tubewells and rainwater harvesting provide safer water than dugwells and pond-sand filters and should be the preferred options.","Risk assessment of arsenic mitigation options in BangladeshAbs: The provision of alternative water sources is the principal arsenic mitigation strategy in Bangladesh, but can lead to risk substitution. A study of arsenic mitigation options was undertaken to assess water quality and sanitary condition and to estimate the burden of disease associated with each technology in disability-adjusted life years (DALYs). Dugwells and pond-sand filters showed heavy microbial contamination in both dry and monsoon seasons, and the estimated burden of disease was high. Rainwater was of good quality in the monsoon but deteriorated in the dry season. Deep tubewells showed microbial contamination in the monsoon but not in the dry season and was the only technology to approach the World Health Organization's reference level of risk of 10(-6) DALYs. A few dugwells and one pond-sand filter showed arsenic in excess of 50 mu g/L. The findings suggest that deep tubewells and rainwater harvesting provide safer water than dugwells and pond-sand filters and should be the preferred options."
244,Jackson 2009,"Chemical Food Safety Issues in the United States: Past, Present, and Future"," Considerable advances have been made over the past century in the understanding of the chemical hazards in food and ways for assessing and managing these risks. At the turn of the 20th century, many Americans were exposed to foods adulterated with toxic compounds. In the 1920s the increasing use of insecticides led to concerns of chronic ingestion of heavy metals such as lead and arsenic from residues remaining on crops. By the 1930s, a variety of agrochemicals were commonly used, and food additives were becoming common in processed foods. During the 1940s and 1950s advances were made in toxicology, and more systematic approaches were adopted for evaluating the safety of chemical contaminants in food. Modern gas chromatography and liquid chromatography, both invented in the 1950s and 1960s, were responsible for progress in detecting, quantifying, and assessing the risk of food contaminants and adulterants. In recent decades, chemical food safety issues that have been the center of media attention include the presence of natural toxins, processing-produced toxins (e.g., acrylamide, heterocyclic aromatic amines, and furan), food allergens, heavy metals (e.g., lead, arsenic, mercury, cadmium), industrial chemicals (e.g., benzene, perchlorate), contaminants from packaging materials, and unconventional contaminants (melamine) in food and feed. Due to the global nature of the food supply and advances in analytical capabilities, chemical contaminants will continue to be an area of concern for regulatory agencies, the food industry, and consumers in the future.","Chemical Food Safety Issues in the United States: Past, Present, and FutureAbs: Considerable advances have been made over the past century in the understanding of the chemical hazards in food and ways for assessing and managing these risks. At the turn of the 20th century, many Americans were exposed to foods adulterated with toxic compounds. In the 1920s the increasing use of insecticides led to concerns of chronic ingestion of heavy metals such as lead and arsenic from residues remaining on crops. By the 1930s, a variety of agrochemicals were commonly used, and food additives were becoming common in processed foods. During the 1940s and 1950s advances were made in toxicology, and more systematic approaches were adopted for evaluating the safety of chemical contaminants in food. Modern gas chromatography and liquid chromatography, both invented in the 1950s and 1960s, were responsible for progress in detecting, quantifying, and assessing the risk of food contaminants and adulterants. In recent decades, chemical food safety issues that have been the center of media attention include the presence of natural toxins, processing-produced toxins (e.g., acrylamide, heterocyclic aromatic amines, and furan), food allergens, heavy metals (e.g., lead, arsenic, mercury, cadmium), industrial chemicals (e.g., benzene, perchlorate), contaminants from packaging materials, and unconventional contaminants (melamine) in food and feed. Due to the global nature of the food supply and advances in analytical capabilities, chemical contaminants will continue to be an area of concern for regulatory agencies, the food industry, and consumers in the future."
245,Kazi et al. 2006,Evaluation of essential and toxic metals by ultrasound-assisted acid leaching from scalp hair samples of children with macular degeneration patients," Background: The causes of night blindness in children are multifactorial and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. Method: An ultrasonic-assisted acid leaching procedure was developed as a sample pretreatment for the determination of Zn, Cu, Cd, As and Pb in human scalp hair samples of night blindness male children with age between 5 to 15 y and compared with the children without vision anomalies that lived in the same localities. The effects of different factors on acid leaching of metals, such as preintensification time (without ultrasonic stirring) after treatment of acid mixture, exposure time to ultrasound and temperature of the ultrasonic bath have been investigated. The proposed method was validated by certified reference samples of scalp hair CRM 397. The wet acid digestion method was used to obtain the total metal concentration in both scalp hair and CRM samples. Cu and Zn in leachates and digests were measured by flame atomic absorption spectrometry (FAAS) using a conventional air/acetylene flame, while Cd and Pb were determined by electrothermal atomic absorption spectrometry (ETAAS) under optimized conditions. Results: It was observed that at optimal conditions, the recovery for Zn, Cd, Pb, As and Cu were 98%, 98.5%, 96%, 97.2% and 94% respectively. The mean values of Zn and Cu in scalp hair samples of children having night blindness were significantly lower as compared to normal healthy children (p for Zn < 0.001 and Cu < 0.003), while the level of toxic metals As, Cd and Pb were significantly higher in children having ocular problems as related to normal children (p As < 0.0074, Cd < 0.001 and lead < 0.004). Conclusion: These data present guidance to clinicians and other professional investigating deficiency of essential trace metals and excessive level of toxic metals in biological samples. (c) 2006 Elsevier B.V. All rights reserved.","Evaluation of essential and toxic metals by ultrasound-assisted acid leaching from scalp hair samples of children with macular degeneration patientsAbs: Background: The causes of night blindness in children are multifactorial and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. Method: An ultrasonic-assisted acid leaching procedure was developed as a sample pretreatment for the determination of Zn, Cu, Cd, As and Pb in human scalp hair samples of night blindness male children with age between 5 to 15 y and compared with the children without vision anomalies that lived in the same localities. The effects of different factors on acid leaching of metals, such as preintensification time (without ultrasonic stirring) after treatment of acid mixture, exposure time to ultrasound and temperature of the ultrasonic bath have been investigated. The proposed method was validated by certified reference samples of scalp hair CRM 397. The wet acid digestion method was used to obtain the total metal concentration in both scalp hair and CRM samples. Cu and Zn in leachates and digests were measured by flame atomic absorption spectrometry (FAAS) using a conventional air/acetylene flame, while Cd and Pb were determined by electrothermal atomic absorption spectrometry (ETAAS) under optimized conditions. Results: It was observed that at optimal conditions, the recovery for Zn, Cd, Pb, As and Cu were 98%, 98.5%, 96%, 97.2% and 94% respectively. The mean values of Zn and Cu in scalp hair samples of children having night blindness were significantly lower as compared to normal healthy children (p for Zn < 0.001 and Cu < 0.003), while the level of toxic metals As, Cd and Pb were significantly higher in children having ocular problems as related to normal children (p As < 0.0074, Cd < 0.001 and lead < 0.004). Conclusion: These data present guidance to clinicians and other professional investigating deficiency of essential trace metals and excessive level of toxic metals in biological samples. (c) 2006 Elsevier B.V. All rights reserved."
246,Kern et al. 2007,Sulfhydryl-reactive metals in autism," This study examined the difference between sulfhydryl- reactive metals ( mercury, lead, arsenic, and cadmium) in the hair of 45 children with autism ( 1 - 6 yr of age) as compared to 45 gender-, age-, and race- matched typical children. Hair samples were measured with inductively coupled mass spectrometry. Some studies, such as Holmes et al. ( 2003), suggested that children with autism may be poor detoxifiers relative to normally developing children. Metals that are not eliminated sequester in the brain. Our study found that arsenic, cadmium, and lead were significantly lower in the hair of children with autism than in matched controls. Mercury was in the same direction ( lower in autism) following the same pattern, but did not achieve statistical significance. The evidence from our study supports the notion that children with autism may have trouble excreting these metals, resulting in a higher body burden that may contribute to symptoms of autism.","Sulfhydryl-reactive metals in autismAbs: This study examined the difference between sulfhydryl- reactive metals ( mercury, lead, arsenic, and cadmium) in the hair of 45 children with autism ( 1 - 6 yr of age) as compared to 45 gender-, age-, and race- matched typical children. Hair samples were measured with inductively coupled mass spectrometry. Some studies, such as Holmes et al. ( 2003), suggested that children with autism may be poor detoxifiers relative to normally developing children. Metals that are not eliminated sequester in the brain. Our study found that arsenic, cadmium, and lead were significantly lower in the hair of children with autism than in matched controls. Mercury was in the same direction ( lower in autism) following the same pattern, but did not achieve statistical significance. The evidence from our study supports the notion that children with autism may have trouble excreting these metals, resulting in a higher body burden that may contribute to symptoms of autism."
247,Lantz et al.  2009,In utero and postnatal exposure to arsenic alters pulmonary structure and function," in addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 mu m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter Pulmonary structure and function in the adults. (C) 2008 Elsevier Inc. All rights reserved.","In utero and postnatal exposure to arsenic alters pulmonary structure and functionAbs: in addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 mu m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter Pulmonary structure and function in the adults. (C) 2008 Elsevier Inc. All rights reserved."
248,Liao et al. 2009,Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality," Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD). but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects. arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful biomarker of arsenic risk. (C) 2008 Elsevier Inc. All rights reserved.","Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormalityAbs: Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD). but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects. arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful biomarker of arsenic risk. (C) 2008 Elsevier Inc. All rights reserved."
249,Lin 2009,"Risk Assessment on Mixture Toxicity of Arsenic, Zinc and Copper Intake from Consumption of Milkfish, Chanos chanos (ForsskAyenl), Cultured Using Contaminated Groundwater in Southwest Taiwan"," Studies on bioaccumulation of arsenic, zinc, and copper in freshwater-cultured milkfish were carried out to assess the risks on human health. The arsenic, zinc, and copper levels in milkfish showed significant positive correlations to the arsenic, zinc, and copper concentrations in pond water. The hazard index of arsenic, zinc, and copper mixture for intake of milkfish (1.75 +/- A 0.65) demonstrated that intake of in this way contaminated milkfish will result in non-carcinogenic risk. The target cancer risk of arsenic for intake of the milkfish (2.74 x 10(-4) +/- A 1.18 x 10(-4)) indicated that the inhabitants were exposed to arsenic pollution with carcinogenic risk.","Risk Assessment on Mixture Toxicity of Arsenic, Zinc and Copper Intake from Consumption of Milkfish, Chanos chanos (ForsskAyenl), Cultured Using Contaminated Groundwater in Southwest TaiwanAbs: Studies on bioaccumulation of arsenic, zinc, and copper in freshwater-cultured milkfish were carried out to assess the risks on human health. The arsenic, zinc, and copper levels in milkfish showed significant positive correlations to the arsenic, zinc, and copper concentrations in pond water. The hazard index of arsenic, zinc, and copper mixture for intake of milkfish (1.75 +/- A 0.65) demonstrated that intake of in this way contaminated milkfish will result in non-carcinogenic risk. The target cancer risk of arsenic for intake of the milkfish (2.74 x 10(-4) +/- A 1.18 x 10(-4)) indicated that the inhabitants were exposed to arsenic pollution with carcinogenic risk."
250,Link et al. 2007,Baden-Wuerttemberg Environmental Health Survey (BW-EHS) from 1996 to 2003: Toxic metals in blood and urine of children," The environmental health surveillance system in the Federal State of Baden-Wuerttemberg (South Germany), among othe rs, was implemented to monitor pollutant exposures and their temporal and regional trends in children at the age of about 10 years. The investigations were performed in two larger cities, one small city and one rural area. Between 1996 and 2003, in total 5470 children were investigated in consideration of environmental health parameters in four cross-sectional studies. The data presented here cover the results of the determination of the internal load with toxic metals. The median values observed in the investigation in 2002/03 were: 4.6 mu g/l urine for arsenic, less than 0.2 mu g/l urine for mercury, 20.7 mu g/l blood for lead, and 0.25 mu g/l blood for cadmium. From 1996 to 2003, mercury concentrations showed a substantial decrease (-0.027 mu g/l/year) and lead levels also decreased (-0.25 mu g/l/year), whereas arsenic and cadmium levels did not change significantly over time. There was no consistent difference in the mean internal load of the metals between the four investigation areas. Important factors influencing the measured concentrations were consumption of fish in the last 48 h, which had an impact on arsenic (factor 2), and amalgam fillings, which accounted for an increase in mercury (factor 4.6). In the 2002/03 study period, levels above the limit of health concern for children (German HBM values) were found in about 0.5% of the lead measurements (maximum value 180 mu g/l blood) and in about 0.2% of the mercury measurements (maximum value 8.2 mu g/l urine). In conclusion, this environmental health survey generates objective data on secular trends and regional differences and provides insight into probable sources of toxic metal exposure in children. (C) 2007 Elsevier GmbH. All rights reserved.","Baden-Wuerttemberg Environmental Health Survey (BW-EHS) from 1996 to 2003: Toxic metals in blood and urine of childrenAbs: The environmental health surveillance system in the Federal State of Baden-Wuerttemberg (South Germany), among othe rs, was implemented to monitor pollutant exposures and their temporal and regional trends in children at the age of about 10 years. The investigations were performed in two larger cities, one small city and one rural area. Between 1996 and 2003, in total 5470 children were investigated in consideration of environmental health parameters in four cross-sectional studies. The data presented here cover the results of the determination of the internal load with toxic metals. The median values observed in the investigation in 2002/03 were: 4.6 mu g/l urine for arsenic, less than 0.2 mu g/l urine for mercury, 20.7 mu g/l blood for lead, and 0.25 mu g/l blood for cadmium. From 1996 to 2003, mercury concentrations showed a substantial decrease (-0.027 mu g/l/year) and lead levels also decreased (-0.25 mu g/l/year), whereas arsenic and cadmium levels did not change significantly over time. There was no consistent difference in the mean internal load of the metals between the four investigation areas. Important factors influencing the measured concentrations were consumption of fish in the last 48 h, which had an impact on arsenic (factor 2), and amalgam fillings, which accounted for an increase in mercury (factor 4.6). In the 2002/03 study period, levels above the limit of health concern for children (German HBM values) were found in about 0.5% of the lead measurements (maximum value 180 mu g/l blood) and in about 0.2% of the mercury measurements (maximum value 8.2 mu g/l urine). In conclusion, this environmental health survey generates objective data on secular trends and regional differences and provides insight into probable sources of toxic metal exposure in children. (C) 2007 Elsevier GmbH. All rights reserved."
251,Lowney et al. 2005,Percutaneous absorption of arsenic from environmental media," Current knowledge of percutancous absorption of arsenic is based on studies of rhesus monkeys using soluble arsenic in aqueous solution, and soluble arsenic mixed with soil (Wester et al., 1993). These studies produced mean dermal absorption rates in the range of 2.0-6.4% of the applied dose. Subsequently, questions arose as to whether these results represent arsenic absorption from environmental media. Factors such as chemical interactions, the presence of other metals, and the effects of weathering on environmental media all can affect the nature of arsenic and its potential for percutancous absorption. Therefore, research specific to more relevant matrices is important. The focus of this effort is to outline study design considerations, including particle size, application rates, means of ensuring skin contact and appropriate statistical evaluation of the data. Appropriate reference groups are also important. The potential for background exposure to arsenic in the diet possibly obscuring a signal from a dermally applied dose of arsenic will also be addressed. We conclude that there are likely to be many site- or sample-specific factors that will control the absorption of arsenic, and matrix-specific analyses may be required to understand the degree of percutaneous absorption. Toxicology and Industrial Health 2005;21: 1-14.","Percutaneous absorption of arsenic from environmental mediaAbs: Current knowledge of percutancous absorption of arsenic is based on studies of rhesus monkeys using soluble arsenic in aqueous solution, and soluble arsenic mixed with soil (Wester et al., 1993). These studies produced mean dermal absorption rates in the range of 2.0-6.4% of the applied dose. Subsequently, questions arose as to whether these results represent arsenic absorption from environmental media. Factors such as chemical interactions, the presence of other metals, and the effects of weathering on environmental media all can affect the nature of arsenic and its potential for percutancous absorption. Therefore, research specific to more relevant matrices is important. The focus of this effort is to outline study design considerations, including particle size, application rates, means of ensuring skin contact and appropriate statistical evaluation of the data. Appropriate reference groups are also important. The potential for background exposure to arsenic in the diet possibly obscuring a signal from a dermally applied dose of arsenic will also be addressed. We conclude that there are likely to be many site- or sample-specific factors that will control the absorption of arsenic, and matrix-specific analyses may be required to understand the degree of percutaneous absorption. Toxicology and Industrial Health 2005;21: 1-14."
252,Lugon-Moulin et al. 2008,Arsenic concentration in tobacco leaves: A study on three commercially important tobacco (Nicotiana tabacum L.) types," In recent years, arsenic (As) has received increased attention as humans may be exposed to it through occupational and environmental exposure. Tobacco (Nicotiana tabacum L.) like other crops can uptake this element from the soil, which may lead to human exposure. Here, we report on a survey on arsenic in cured or processed tobacco leaves obtained from Africa, Asia, Europe, South and North America. A total of 1,431 leaf samples of flue-cured, burley, and Oriental tobaccos were obtained from various sampling locations during 2002 to 2004. Arsenic concentration in the samples averaged 0.4 +/- 0.6 mu g g(-1) as determined by inductively coupled plasma-mass spectrometry. Recorded values from most samples showed that concentrations of arsenic were usually found at the lower end of the distribution. Significant differences were found among tobacco types, sampling locations, and crop years. Arsenic concentrations were rather low in the majority of regions investigated, which is compatible with data from the literature. However, sample size was small and sampling geographically restricted. Our results would need to be validated with a larger dataset.","Arsenic concentration in tobacco leaves: A study on three commercially important tobacco (Nicotiana tabacum L.) typesAbs: In recent years, arsenic (As) has received increased attention as humans may be exposed to it through occupational and environmental exposure. Tobacco (Nicotiana tabacum L.) like other crops can uptake this element from the soil, which may lead to human exposure. Here, we report on a survey on arsenic in cured or processed tobacco leaves obtained from Africa, Asia, Europe, South and North America. A total of 1,431 leaf samples of flue-cured, burley, and Oriental tobaccos were obtained from various sampling locations during 2002 to 2004. Arsenic concentration in the samples averaged 0.4 +/- 0.6 mu g g(-1) as determined by inductively coupled plasma-mass spectrometry. Recorded values from most samples showed that concentrations of arsenic were usually found at the lower end of the distribution. Significant differences were found among tobacco types, sampling locations, and crop years. Arsenic concentrations were rather low in the majority of regions investigated, which is compatible with data from the literature. However, sample size was small and sampling geographically restricted. Our results would need to be validated with a larger dataset."
253,Luo et al. 2009,"Effects of arsenic exposure from drinking water on spatial memory, ultra-structures and NMDAR gene expression of hippocampus in rats"," Epidemiological investigations indicate that chronic arsenic exposure call damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-D-aspartate receptor (NMDAR) gene expression in rats. Sprague-Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L. (group B) and 68 mg/L(group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory Status. Samples of hippocampus Were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L Caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus. (C) 2008 Published by Elsevier Ireland Ltd.","Effects of arsenic exposure from drinking water on spatial memory, ultra-structures and NMDAR gene expression of hippocampus in ratsAbs: Epidemiological investigations indicate that chronic arsenic exposure call damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-D-aspartate receptor (NMDAR) gene expression in rats. Sprague-Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L. (group B) and 68 mg/L(group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory Status. Samples of hippocampus Were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L Caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus. (C) 2008 Published by Elsevier Ireland Ltd."
254,Marsh et al. 2009,"Mortality patterns among workers exposed to arsenic, cadmium, and other substances in a copper smelter"," Objective To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide stud) Methods Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO2, arsenic, cadmium, dust, and cobalt. We computed standardized mortality, ratios (SMRs) based oil U.S. and local county rates and modeled internal relative risks (RRs). Results We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality, risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure-response relationship for cadmium exposure and bronchitis. Conclusions Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding or effect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility. Am. J. Ind. Med. 52:633-644, 2009. (C) 2009 Wiley-Liss, Inc.","Mortality patterns among workers exposed to arsenic, cadmium, and other substances in a copper smelterAbs: Objective To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide stud) Methods Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO2, arsenic, cadmium, dust, and cobalt. We computed standardized mortality, ratios (SMRs) based oil U.S. and local county rates and modeled internal relative risks (RRs). Results We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality, risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure-response relationship for cadmium exposure and bronchitis. Conclusions Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding or effect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility. Am. J. Ind. Med. 52:633-644, 2009. (C) 2009 Wiley-Liss, Inc."
255,Marti-Cid et al. 2009,"Dietary Exposure to Metals by Individuals Living Near a Hazardous Waste Incinerator in Catalonia, Spain: Temporal Trend"," The concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl), and vanadium (V) were determined in a number of foodstuffs purchased during 2006 in various localities of Tarragona County (Catalonia, Spain), near a hazardous waste incinerator, which has been operating since 1999. The dietary intake of the above elements by the population of the area was subsequently estimated. The results were compared with those obtained in previous surveys (baseline 1997 and 2002) performed in the same area. The levels of Be, Tl, and V were under their respective limits of detection in all samples. The estimated dietary intakes of the elements analyzed in the current survey by an adult man of 70 kg were the following: 351 mu g/day for As, 4.6 mu g/day for Cd, 57.5 mu g/day for Cr, 7.1 mu g/day for Hg, 2,229 mu g/day for Mn, 78.0 mu g/day for Ni, 39.9 mu g/day for Pb, and 37.9 mu g/day for Sn. On average, fish and seafood were the main contributor to the total dietary intake of As, Cd, and Hg and one of the most important for Pb. In general terms, the differences on metal exposure through dietary intake between the present and our two previous surveys were not particularly relevant. The current intake of the most toxic elements (As, Cd, Hg, and Pb) remains under the respective Provisional Tolerable Weekly Intakes established by the Food and Agriculture Organization/World Health Organization.","Dietary Exposure to Metals by Individuals Living Near a Hazardous Waste Incinerator in Catalonia, Spain: Temporal TrendAbs: The concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl), and vanadium (V) were determined in a number of foodstuffs purchased during 2006 in various localities of Tarragona County (Catalonia, Spain), near a hazardous waste incinerator, which has been operating since 1999. The dietary intake of the above elements by the population of the area was subsequently estimated. The results were compared with those obtained in previous surveys (baseline 1997 and 2002) performed in the same area. The levels of Be, Tl, and V were under their respective limits of detection in all samples. The estimated dietary intakes of the elements analyzed in the current survey by an adult man of 70 kg were the following: 351 mu g/day for As, 4.6 mu g/day for Cd, 57.5 mu g/day for Cr, 7.1 mu g/day for Hg, 2,229 mu g/day for Mn, 78.0 mu g/day for Ni, 39.9 mu g/day for Pb, and 37.9 mu g/day for Sn. On average, fish and seafood were the main contributor to the total dietary intake of As, Cd, and Hg and one of the most important for Pb. In general terms, the differences on metal exposure through dietary intake between the present and our two previous surveys were not particularly relevant. The current intake of the most toxic elements (As, Cd, Hg, and Pb) remains under the respective Provisional Tolerable Weekly Intakes established by the Food and Agriculture Organization/World Health Organization."
256,Martin-Diaz et al. 2007,Biomarkers study for sediment quality assessment in Spanish ports using the crab Carcinus maenas and the clam Ruditapes philippinarum," Intermolt crab Carcinus maenas and clam Ruditapes philippinarum were used to determine the toxicity of sediments collected in four Spanish ports (Cadiz, Huelva, Pasajes, and Bilbao) under laboratory conditions during 28 days. Sediment samples were analyzed to determine chemical concentration of metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn), polyaromatic hydrocarbons, polychlorinated biphenyls, grain size distribution, and organic matter content. Different biomarkers of exposure of early biological stress were determined after 28-day exposure in crabs and clams, in the hepatopancreas and in the digestive gland, respectively: metallothionein, ethoxyresorufin O-deethylase (EROD), glutathione peroxidase (GPX), glutathione S-transferase (GST), and glutathione reductase activities (GR). The battery of biomarkers tested resulted in showing and linking the bioavailability of various contaminants and sediment characteristics to the toxicity of the different sediments. Significant induction of MTs was observed when organisms were exposed to metal-contaminated sediments (port of Huelva), and induction of EROD and GPX activities after exposure to sediments containing organic compounds (port of Bilbao and Pasajes). Higher induction was shown in biomarkers tested in crabs; nevertheless, only interspecies significant differences were observed in the induction of GR and GST activities. The present work confirms the necessity of using species with different ecological lifestyles for sediment toxicity assessment and validates the use of this set of biomarkers as a potential tool in sediment toxicity assessment.","Biomarkers study for sediment quality assessment in Spanish ports using the crab Carcinus maenas and the clam Ruditapes philippinarumAbs: Intermolt crab Carcinus maenas and clam Ruditapes philippinarum were used to determine the toxicity of sediments collected in four Spanish ports (Cadiz, Huelva, Pasajes, and Bilbao) under laboratory conditions during 28 days. Sediment samples were analyzed to determine chemical concentration of metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn), polyaromatic hydrocarbons, polychlorinated biphenyls, grain size distribution, and organic matter content. Different biomarkers of exposure of early biological stress were determined after 28-day exposure in crabs and clams, in the hepatopancreas and in the digestive gland, respectively: metallothionein, ethoxyresorufin O-deethylase (EROD), glutathione peroxidase (GPX), glutathione S-transferase (GST), and glutathione reductase activities (GR). The battery of biomarkers tested resulted in showing and linking the bioavailability of various contaminants and sediment characteristics to the toxicity of the different sediments. Significant induction of MTs was observed when organisms were exposed to metal-contaminated sediments (port of Huelva), and induction of EROD and GPX activities after exposure to sediments containing organic compounds (port of Bilbao and Pasajes). Higher induction was shown in biomarkers tested in crabs; nevertheless, only interspecies significant differences were observed in the induction of GR and GST activities. The present work confirms the necessity of using species with different ecological lifestyles for sediment toxicity assessment and validates the use of this set of biomarkers as a potential tool in sediment toxicity assessment."
257,Mateo et al. 2006,"Altered porphyrin excretion and histopathology of greylag geese (Anser anser) exposed to soil contaminated with lead and arsenic in the Guadalquivir Marshes, southwestern Spain"," Greylag geese (Anser anser) in the Guadalquivir Marshes (southwestern Spain) can be exposed to sources of inorganic pollution such as heavy metals and arsenic from mining activities or Pb shot used for hunting. We have sampled 270 fecal excreta in different areas of the marshes in 2001 to 2002 to evaluate the exposure to Pb, Zn, Cu, Mn, and As and to determine its relationship with soil ingestion and with the excretion of porphyrins and biliverdin as biomarkers. These effects and the histopathology of liver, kidney, and pancreas were also studied in 50 geese shot in 2002 to 2004. None of the geese had ingested Pb shot in the gizzard. This contrasts with earlier samplings before the ban of Pb shot for waterfowl hunting in 2001 and the removal of Pb shot in points of the Donana National Park (Spain) in 1999 to 2000. The highest exposure through direct soil ingestion to Pb and other studied elements was observed in samples from Entremuros, the area of the Donana Natural Park affected by the Aznalcollar mine spill in 1998. Birds from Entremuros also more frequently showed mononuclear infiltrates in liver and kidney than birds from the unaffected areas, although other more specific lesions of Pb or Zn poisoning were not observed. The excretion of coproporphyrins, especially of the isomer 1, was positively related to the fecal As concentration, and the ratio of coproporphyrin III/I was positively related to fecal Pb concentration. Biliary protoporphyrin IX concentration was also slightly related to hepatic Pb concentration. This study reflects biological effects on terrestrial animals by the mining pollution in Donana that can be monitored with the simple noninvasive sampling of feces.","Altered porphyrin excretion and histopathology of greylag geese (Anser anser) exposed to soil contaminated with lead and arsenic in the Guadalquivir Marshes, southwestern SpainAbs: Greylag geese (Anser anser) in the Guadalquivir Marshes (southwestern Spain) can be exposed to sources of inorganic pollution such as heavy metals and arsenic from mining activities or Pb shot used for hunting. We have sampled 270 fecal excreta in different areas of the marshes in 2001 to 2002 to evaluate the exposure to Pb, Zn, Cu, Mn, and As and to determine its relationship with soil ingestion and with the excretion of porphyrins and biliverdin as biomarkers. These effects and the histopathology of liver, kidney, and pancreas were also studied in 50 geese shot in 2002 to 2004. None of the geese had ingested Pb shot in the gizzard. This contrasts with earlier samplings before the ban of Pb shot for waterfowl hunting in 2001 and the removal of Pb shot in points of the Donana National Park (Spain) in 1999 to 2000. The highest exposure through direct soil ingestion to Pb and other studied elements was observed in samples from Entremuros, the area of the Donana Natural Park affected by the Aznalcollar mine spill in 1998. Birds from Entremuros also more frequently showed mononuclear infiltrates in liver and kidney than birds from the unaffected areas, although other more specific lesions of Pb or Zn poisoning were not observed. The excretion of coproporphyrins, especially of the isomer 1, was positively related to the fecal As concentration, and the ratio of coproporphyrin III/I was positively related to fecal Pb concentration. Biliary protoporphyrin IX concentration was also slightly related to hepatic Pb concentration. This study reflects biological effects on terrestrial animals by the mining pollution in Donana that can be monitored with the simple noninvasive sampling of feces."
258,Mazumder 2007,Arsenic and non-malignant lung disease," Many aquifers in various parts of the world have been found to be contaminated with arsenic at concentration above 0.05 mg/L. However reports of large number of affected people in India and Bangladesh are unprecedented. Characteristic skin lesions (pigmentation, depigmentation and keratosis) are the hallmark signs of chronic arsenic toxicity. Emerging evidences show that ingestion of arsenic through drinking water may also lead to non-malignant respiratory effects. Early report of non-malignant pulmonary effect of chronic ingestion of arsenic was available from studies in children in Chile as early as 1970. However on the basis of case studies, respiratory effect of chronic arsenic toxicity in adults following dinking of arsenic contaminated water in West Bengal was first reported in 1997. Epidemiological studies carried out in West Bengal on a population of 7683 showed that the prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic induced skin lesions who also had high levels of arsenic in their current drinking water source (>= 0.5 mg/L) compared with individuals who had normal skin and were exposed to low levels of arsenic (<0.05 mg/L). In participants with skin lesions, age-adjusted POR estimates for chronic cough were 7.8 for females (95% CI:3.1-19.5) and 5.0 for males (95% 0:2.6-9.9). In Bangladesh, similar study carried out on a population of 218 showed that the crude prevalence ratio for chronic bronchitis was found to be 10.3 (95% CI:2.4-43. 1) for females and 1.6 (95% CI:0.8-3. 1) for males. Reports of lung function tests were available from both hospital and population based studies. Results show evidences of restrictive, obstructive and combined obstructive and restrictive lung disease in different people having chronic lung disease associated with chronic arsenic toxicity. On the basis of clinical study, chest X-ray and HRCT done in Arsenicosis patients with features of chronic lung disease, the abnormalities observed were varied. Evidences of obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and bronchiectasis were found in some of the cases. Results of studies carried out on people showing features of Arsenicosis due to drinking arsenic contaminated water provide evidence that arsenic is a potent respiratory toxicant, even following ingestion.","Arsenic and non-malignant lung diseaseAbs: Many aquifers in various parts of the world have been found to be contaminated with arsenic at concentration above 0.05 mg/L. However reports of large number of affected people in India and Bangladesh are unprecedented. Characteristic skin lesions (pigmentation, depigmentation and keratosis) are the hallmark signs of chronic arsenic toxicity. Emerging evidences show that ingestion of arsenic through drinking water may also lead to non-malignant respiratory effects. Early report of non-malignant pulmonary effect of chronic ingestion of arsenic was available from studies in children in Chile as early as 1970. However on the basis of case studies, respiratory effect of chronic arsenic toxicity in adults following dinking of arsenic contaminated water in West Bengal was first reported in 1997. Epidemiological studies carried out in West Bengal on a population of 7683 showed that the prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic induced skin lesions who also had high levels of arsenic in their current drinking water source (>= 0.5 mg/L) compared with individuals who had normal skin and were exposed to low levels of arsenic (<0.05 mg/L). In participants with skin lesions, age-adjusted POR estimates for chronic cough were 7.8 for females (95% CI:3.1-19.5) and 5.0 for males (95% 0:2.6-9.9). In Bangladesh, similar study carried out on a population of 218 showed that the crude prevalence ratio for chronic bronchitis was found to be 10.3 (95% CI:2.4-43. 1) for females and 1.6 (95% CI:0.8-3. 1) for males. Reports of lung function tests were available from both hospital and population based studies. Results show evidences of restrictive, obstructive and combined obstructive and restrictive lung disease in different people having chronic lung disease associated with chronic arsenic toxicity. On the basis of clinical study, chest X-ray and HRCT done in Arsenicosis patients with features of chronic lung disease, the abnormalities observed were varied. Evidences of obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and bronchiectasis were found in some of the cases. Results of studies carried out on people showing features of Arsenicosis due to drinking arsenic contaminated water provide evidence that arsenic is a potent respiratory toxicant, even following ingestion."
259,Meeker et al. 2009,Multiple metals predict prolactin and thyrotropin (TSH) levels in men," Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications. (C) 2009 Elsevier Inc. All rights reserved.","Multiple metals predict prolactin and thyrotropin (TSH) levels in menAbs: Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications. (C) 2009 Elsevier Inc. All rights reserved."
260,Misbahuddin et al. 2006,Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: A randomized placebo-controlled study," Background . Millions of people in Bangladesh, India, Taiwan, and Chile are consuming high concentration of arsenic through drinking water, and thousands of them have already developed chronic arsenic poisoning. There is no specific treatment. Some authors suggest the use of vitamins and minerals for more than 6 months. The present placebo-controlled double-blind study was conducted to evaluate effectiveness of spirulina extract plus zinc in the treatment of chronic arsenic poisoning. Methods . Forty-one patients of chronic arsenic poisoning were randomly treated orally by either placebo (17 patients) or spirulina extract (250 mg) plus zinc (2 mg) (24 patients) twice daily for 16 weeks. Each patient was supplied with arsenic-safe drinking water by installing a locally made water filter at household level. Effectiveness of spirulina extract plus zinc was evaluated by comparing changes in skin manifestations (clinical scores), arsenic contents in urine and hair, between the placebo- and spirulina extract plus zinc-treated groups. Results . The concentrations of total arsenic in water (without filtration) of placebo- and spirulina extract plus zinc-treated groups were 150.1 +/- 18.3 and 161.7 +/- 23.9 mu g/l, respectively. Intake of these high concentrations of arsenic lead to increased excretion of arsenic in urine (72.1 +/- 14.5 mu g/l in placebo-treated group and 78.4 +/- 19.1 mu g/l in spirulina plus zinc-treated group). After 2 weeks of using filtered water, there were significant reduction of both arsenic intake through water and urinary arsenic excretion (8.3 +/- 3.6 mu g/l and 18.4 +/- 7.3 mu g/l in placebo group; 9.7 +/- 5.4 mu g/l and 21.6 +/- 5.8 mu g/l) in spirulina extract plus zinc-treated group. There was a sharp increase in urinary excretion of arsenic (138 +/- 43.6 mu g/l) at 4 weeks following spirulina plus zinc administration and the effect was continued for another 2 weeks. Spirulina extract plus zinc removed 47.1% arsenic from scalp hair. Spirulina extract had no major adverse effect that required physician's attention. The clinical scores (median) for melanosis before and after treatment with placebo was not statistically significant (p>0.05), whereas in spirulina extract plus zinc-treated group it was statistically significant (p<0.01). In cases of keratosis, the median clinical scores before and after treatment was not statistically significant (p>0.05) in placebo-treated group. In spirulina extract plus zinc-treated group, the clinical scores for keratosis before and after treatment was statistically significant (p<0.05). Conclusions: Results show that spirulina extract (250 mg) plus zinc (2 mg) twice daily for 16 weeks may be useful for the treatment of chronic arsenic poisoning with melanosis and keratosis.","Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: A randomized placebo-controlled studyAbs: Background . Millions of people in Bangladesh, India, Taiwan, and Chile are consuming high concentration of arsenic through drinking water, and thousands of them have already developed chronic arsenic poisoning. There is no specific treatment. Some authors suggest the use of vitamins and minerals for more than 6 months. The present placebo-controlled double-blind study was conducted to evaluate effectiveness of spirulina extract plus zinc in the treatment of chronic arsenic poisoning. Methods . Forty-one patients of chronic arsenic poisoning were randomly treated orally by either placebo (17 patients) or spirulina extract (250 mg) plus zinc (2 mg) (24 patients) twice daily for 16 weeks. Each patient was supplied with arsenic-safe drinking water by installing a locally made water filter at household level. Effectiveness of spirulina extract plus zinc was evaluated by comparing changes in skin manifestations (clinical scores), arsenic contents in urine and hair, between the placebo- and spirulina extract plus zinc-treated groups. Results . The concentrations of total arsenic in water (without filtration) of placebo- and spirulina extract plus zinc-treated groups were 150.1 +/- 18.3 and 161.7 +/- 23.9 mu g/l, respectively. Intake of these high concentrations of arsenic lead to increased excretion of arsenic in urine (72.1 +/- 14.5 mu g/l in placebo-treated group and 78.4 +/- 19.1 mu g/l in spirulina plus zinc-treated group). After 2 weeks of using filtered water, there were significant reduction of both arsenic intake through water and urinary arsenic excretion (8.3 +/- 3.6 mu g/l and 18.4 +/- 7.3 mu g/l in placebo group; 9.7 +/- 5.4 mu g/l and 21.6 +/- 5.8 mu g/l) in spirulina extract plus zinc-treated group. There was a sharp increase in urinary excretion of arsenic (138 +/- 43.6 mu g/l) at 4 weeks following spirulina plus zinc administration and the effect was continued for another 2 weeks. Spirulina extract plus zinc removed 47.1% arsenic from scalp hair. Spirulina extract had no major adverse effect that required physician's attention. The clinical scores (median) for melanosis before and after treatment with placebo was not statistically significant (p>0.05), whereas in spirulina extract plus zinc-treated group it was statistically significant (p<0.01). In cases of keratosis, the median clinical scores before and after treatment was not statistically significant (p>0.05) in placebo-treated group. In spirulina extract plus zinc-treated group, the clinical scores for keratosis before and after treatment was statistically significant (p<0.05). Conclusions: Results show that spirulina extract (250 mg) plus zinc (2 mg) twice daily for 16 weeks may be useful for the treatment of chronic arsenic poisoning with melanosis and keratosis."
261,Modi et al. 2005,Arsenic antagonism studies with monoisoamyl DMSA and zinc in male mice," Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2 mg kg(-1) arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10 mg kg(-1), zinc (as zinc acetate, orally), 50 mg kg(-1) monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.). 2 h after arsenic administration. Another group of arsenic treated animals was given both zinc (10 mg kg(-1)) and MiADMSA (50 mg kg-1, p.o.). Animals were sacrificed 24 h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2 mg kg(-1), i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD). depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while. zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most Of the biochemical variables indicative of hepatic oxidative stress responded favorably to MiADMSA treatment while, zinc administration had no effect. Administration of MiADMSA significantly depleted arsenic concentration from the soft tissues while, combined zinc and MiADMSA had no additional beneficial effect over the individual effect of MiADMSA. The results thus lead us to conclude that in order to achieve best effects of chelation therapy, co-administration of zinc with chelator might be preferred. However. detailed experimental studies with variable doses and after chronic arsenic exposure are required. (C) 2004 Elsevier B.V. All rights reserved.","Arsenic antagonism studies with monoisoamyl DMSA and zinc in male miceAbs: Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2 mg kg(-1) arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10 mg kg(-1), zinc (as zinc acetate, orally), 50 mg kg(-1) monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.). 2 h after arsenic administration. Another group of arsenic treated animals was given both zinc (10 mg kg(-1)) and MiADMSA (50 mg kg-1, p.o.). Animals were sacrificed 24 h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2 mg kg(-1), i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD). depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while. zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most Of the biochemical variables indicative of hepatic oxidative stress responded favorably to MiADMSA treatment while, zinc administration had no effect. Administration of MiADMSA significantly depleted arsenic concentration from the soft tissues while, combined zinc and MiADMSA had no additional beneficial effect over the individual effect of MiADMSA. The results thus lead us to conclude that in order to achieve best effects of chelation therapy, co-administration of zinc with chelator might be preferred. However. detailed experimental studies with variable doses and after chronic arsenic exposure are required. (C) 2004 Elsevier B.V. All rights reserved."
262,Morachevskii and Butukhanova 2009,Interaction of Aluminum with Admixtures Dissolved in Liquid Lead," The behavior of antimony, tin, copper, bismuth, and arsenic admixtures during refining black lead with aluminum application was considered.","Interaction of Aluminum with Admixtures Dissolved in Liquid LeadAbs: The behavior of antimony, tin, copper, bismuth, and arsenic admixtures during refining black lead with aluminum application was considered."
263,Nadal et al. 2008,"Exposure to metals through the consumption of fish and seafood by the population living near the Ebro River in Catalonia, Spain: Health risks"," The health risks due to metal exposure from consuming various fish and seafood species were assessed for the Catalan population living near the Ebro River (Spain). The concentrations of arsenic, cadmium, chromium, copper, mercury, manganese, nickel, and lead were determined in samples of mussel, clam, hake, sole, cuttlefish, sardine, and anchovy randomly acquired in various localities of the zone under evaluation. In general terms, metal concentrations were similar or lower than the levels recently reported in the literature. The current dietary intake of metals is analogous to that recently estimated for the non-exposed population of Catalonia. Metal exposure through fish and seafood consumption would only mean a slight increase of noncarcinogenic and carcinogenic risk for arsenic, whereas the remaining elements showed risk values below the corresponding threshold levels.","Exposure to metals through the consumption of fish and seafood by the population living near the Ebro River in Catalonia, Spain: Health risksAbs: The health risks due to metal exposure from consuming various fish and seafood species were assessed for the Catalan population living near the Ebro River (Spain). The concentrations of arsenic, cadmium, chromium, copper, mercury, manganese, nickel, and lead were determined in samples of mussel, clam, hake, sole, cuttlefish, sardine, and anchovy randomly acquired in various localities of the zone under evaluation. In general terms, metal concentrations were similar or lower than the levels recently reported in the literature. The current dietary intake of metals is analogous to that recently estimated for the non-exposed population of Catalonia. Metal exposure through fish and seafood consumption would only mean a slight increase of noncarcinogenic and carcinogenic risk for arsenic, whereas the remaining elements showed risk values below the corresponding threshold levels."
264,Obiri 2007,Determination of heavy metals in water from boreholes in Dumasi in the Wassa West District of western region of Republic of Ghana," Concentrations of heavy metals in the borehole at Dumasi in the Wassa West District of the Republic of Ghana have been measured in this study. The concentrations of the following metals in the ground water from Dumasi borehole are: Iron (Fe) - 7.52 ppm, Manganese (Mn) - 1.11 ppm, Arsenic (As) - 4.52 ppm, Chromium (Cr) - 0.026 ppm, Cobalt (Co) - 0.01 ppm, Zinc (Zn) - 0.007 ppm, Cadmium (Cd) - 0.002 ppm and Lead (Pb) - 0.005 ppm. The results of the study show that resident adults and children who use water from the boreholes are at serious risk from exposure to health hazards associated with exposure to the above metals in the boreholes in Dumasi. If the results of this study are applied to other mining communities, which lie on the Birimian and Tarkwaian rock system, then the residents are at serious risk from exposure to toxic metals from drinking water from the boreholes dug for them by mining companies operating in their communities.","Determination of heavy metals in water from boreholes in Dumasi in the Wassa West District of western region of Republic of GhanaAbs: Concentrations of heavy metals in the borehole at Dumasi in the Wassa West District of the Republic of Ghana have been measured in this study. The concentrations of the following metals in the ground water from Dumasi borehole are: Iron (Fe) - 7.52 ppm, Manganese (Mn) - 1.11 ppm, Arsenic (As) - 4.52 ppm, Chromium (Cr) - 0.026 ppm, Cobalt (Co) - 0.01 ppm, Zinc (Zn) - 0.007 ppm, Cadmium (Cd) - 0.002 ppm and Lead (Pb) - 0.005 ppm. The results of the study show that resident adults and children who use water from the boreholes are at serious risk from exposure to health hazards associated with exposure to the above metals in the boreholes in Dumasi. If the results of this study are applied to other mining communities, which lie on the Birimian and Tarkwaian rock system, then the residents are at serious risk from exposure to toxic metals from drinking water from the boreholes dug for them by mining companies operating in their communities."
265,Pawlak et al. 2008,Study of arsenic content in mine groundwater commonly used for human consumption in Utah," Of the various sources of arsenic released in to the environment, the presence of arsenic in water probably poses the greatest threat to human health. Arsenic is released in to the environment through water by dissolution of minerals and ores. Natural release is slow, but in some areas the concentration of arsenic in groundwater (commonly referred to as Acid Mine Drainage (or AMD)) is accelerated by mining activity. In fact the presence of arsenic may last a long time even after the mining activity has ceased. Hence it is imperative to study the quality of water (especially for those areas in the vicinity of mines) used for different purposes to identify an appropriate remediation technique for effective pollution control. In this paper, contents of arsenic and other metals in the water were quantified from three different sources: (1) groundwater from the mining tunnel (judge tunnel), (2) drinking water, and (3) water used in the hydrant-flushed distribution system (Park City) in Utah (USA). The results showed the content of arsenic from the mining tunnel, after chlorination, and in tap water were below 10 mu g l(-1). However, significant amounts of arsenic, lead, zinc, iron, manganese and antimony have been found in water samples taken from the distribution systems. In the consideration of the further use of mine groundwater for drinking purposes and the distribution system, Park City should regularly be maintained by a flushing program in the distribution system.","Study of arsenic content in mine groundwater commonly used for human consumption in UtahAbs: Of the various sources of arsenic released in to the environment, the presence of arsenic in water probably poses the greatest threat to human health. Arsenic is released in to the environment through water by dissolution of minerals and ores. Natural release is slow, but in some areas the concentration of arsenic in groundwater (commonly referred to as Acid Mine Drainage (or AMD)) is accelerated by mining activity. In fact the presence of arsenic may last a long time even after the mining activity has ceased. Hence it is imperative to study the quality of water (especially for those areas in the vicinity of mines) used for different purposes to identify an appropriate remediation technique for effective pollution control. In this paper, contents of arsenic and other metals in the water were quantified from three different sources: (1) groundwater from the mining tunnel (judge tunnel), (2) drinking water, and (3) water used in the hydrant-flushed distribution system (Park City) in Utah (USA). The results showed the content of arsenic from the mining tunnel, after chlorination, and in tap water were below 10 mu g l(-1). However, significant amounts of arsenic, lead, zinc, iron, manganese and antimony have been found in water samples taken from the distribution systems. In the consideration of the further use of mine groundwater for drinking purposes and the distribution system, Park City should regularly be maintained by a flushing program in the distribution system."
266,Rios-Arana et al. 2005,Heat shock protein 60 (HSP60) response of Plationus patulus (Rotifera: Monogononta) to combined exposures of arsenic and heavy metals," Organisms produce stress proteins as a response to natural and anthropogenic environmental changes. Induction of stress proteins has been reported in a variety of aquatic organisms, including rotifers, exposed to pollutants. Past studies on stress protein responses of rotifers have focused on exposure to single toxicants. In this study the rotifer Plationus patulus was exposed singly and in combination to various concentrations of As, Cr, Cu, Ni, Ph, and Zn. Following exposure, total protein was quantified (Bradford method) and stress protein 60 (HSP60) was identified using Western blotting. P. patulus induced HSP60 as a response to single exposures to Cr, Cu, Ni, Pb and Zn. HSP60 expression was increased (2 fold) in rotifers exposed to these single elements at both low and high concentrations as compared to unexposed rotifers. Arsenic exposure resulted in a 2 fold decrease in HSP induction. In rotifers exposed to metal mixtures, HSP60 was induced by the presence of As-Zn, As-Cr-Cu-Pb, As-Cr-Cu, As-Cr-Cu-Ni and As-Cr-CuNi-Pb combinations in the media. HSP60 response to As and heavy metals toxicity depends on the type and number of elements present in the media as well as their concentrations and length of the exposure time.","Heat shock protein 60 (HSP60) response of Plationus patulus (Rotifera: Monogononta) to combined exposures of arsenic and heavy metalsAbs: Organisms produce stress proteins as a response to natural and anthropogenic environmental changes. Induction of stress proteins has been reported in a variety of aquatic organisms, including rotifers, exposed to pollutants. Past studies on stress protein responses of rotifers have focused on exposure to single toxicants. In this study the rotifer Plationus patulus was exposed singly and in combination to various concentrations of As, Cr, Cu, Ni, Ph, and Zn. Following exposure, total protein was quantified (Bradford method) and stress protein 60 (HSP60) was identified using Western blotting. P. patulus induced HSP60 as a response to single exposures to Cr, Cu, Ni, Pb and Zn. HSP60 expression was increased (2 fold) in rotifers exposed to these single elements at both low and high concentrations as compared to unexposed rotifers. Arsenic exposure resulted in a 2 fold decrease in HSP induction. In rotifers exposed to metal mixtures, HSP60 was induced by the presence of As-Zn, As-Cr-Cu-Pb, As-Cr-Cu, As-Cr-Cu-Ni and As-Cr-CuNi-Pb combinations in the media. HSP60 response to As and heavy metals toxicity depends on the type and number of elements present in the media as well as their concentrations and length of the exposure time."
267,Schulz et al. 2007,Twenty years of the German Environmental Survey (GerES): Human biomonitoring - Temporal and spatial (West Germany/East Germany) differences in population exposure," The German Environmental Surveys (GerESs) are nationwide population studies, which have repeatedly been carried out in Germany since the mid-1980s. The subjects were representatively selected from the regional registration offices with regard to age, gender and community size. The first survey for adults (GerES I) was carried out in 1985/1986 (West Germany) followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). In GerES II children were also included to some extent. In 1998, the third GerES for adults was conducted in both parts of Germany (GerES III). The current survey 2003/2006 (GerES IV) is focussing exclusively on children. A 1-year pilot study was conducted in 2001-2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study. The main goal of the surveys is to analyse and document the extent, distribution and determinants of exposure to environmental pollutants of the German general population. Three main instruments of investigation were comprised in GerES: human biomonitoring (HBM), monitoring of the domestic environment, and collecting information on exposure pathways and living conditions via questionnaires. This paper is focussed on the general design of the GerESs, the trend over time and spatial differences (West Germany and East Germany) for HBM data on arsenic, cadmium, lead, mercury, pentachlorophenol (PCP), and polycyclic aromatic hydrocarbons (PAH). These substances have been determined in blood and/or morning urine of adults and children. All GerESs have been conducted in close connection with the National Health Interview and Examination Surveys performed by the Robert Koch-Institute, Berlin. (C) 2007 Elsevier GmbH. All rights reserved.","Twenty years of the German Environmental Survey (GerES): Human biomonitoring - Temporal and spatial (West Germany/East Germany) differences in population exposureAbs: The German Environmental Surveys (GerESs) are nationwide population studies, which have repeatedly been carried out in Germany since the mid-1980s. The subjects were representatively selected from the regional registration offices with regard to age, gender and community size. The first survey for adults (GerES I) was carried out in 1985/1986 (West Germany) followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). In GerES II children were also included to some extent. In 1998, the third GerES for adults was conducted in both parts of Germany (GerES III). The current survey 2003/2006 (GerES IV) is focussing exclusively on children. A 1-year pilot study was conducted in 2001-2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study. The main goal of the surveys is to analyse and document the extent, distribution and determinants of exposure to environmental pollutants of the German general population. Three main instruments of investigation were comprised in GerES: human biomonitoring (HBM), monitoring of the domestic environment, and collecting information on exposure pathways and living conditions via questionnaires. This paper is focussed on the general design of the GerESs, the trend over time and spatial differences (West Germany and East Germany) for HBM data on arsenic, cadmium, lead, mercury, pentachlorophenol (PCP), and polycyclic aromatic hydrocarbons (PAH). These substances have been determined in blood and/or morning urine of adults and children. All GerESs have been conducted in close connection with the National Health Interview and Examination Surveys performed by the Robert Koch-Institute, Berlin. (C) 2007 Elsevier GmbH. All rights reserved."
268,Spalding et al. 2009,The Metabolic Syndrome: A Modern Plague Spread by Modern Technology," Malnutrition and infectious disease represent the most common health threats facing the developing world. However, increasing technological developments and the expansion of western culture have contributed to the increasing prevalence of the metabolic syndrome. The epidemiologic significance and potential costs to governmental health care systems of an increasing incidence of metabolic syndrome could become high. The role of environmental influences that lead to the development of the metabolic syndrome needs to be explored. Because the metabolic syndrome becomes more common as nations develop, investigations into the ramifications of this disease often come too late.","The Metabolic Syndrome: A Modern Plague Spread by Modern TechnologyAbs: Malnutrition and infectious disease represent the most common health threats facing the developing world. However, increasing technological developments and the expansion of western culture have contributed to the increasing prevalence of the metabolic syndrome. The epidemiologic significance and potential costs to governmental health care systems of an increasing incidence of metabolic syndrome could become high. The role of environmental influences that lead to the development of the metabolic syndrome needs to be explored. Because the metabolic syndrome becomes more common as nations develop, investigations into the ramifications of this disease often come too late."
269,Steinmaus et al. 2005,Intraindividual variability in arsenic methylation in a US population," Several recent investigations have reported associations between a reduced capacity to fully methylate inorganic arsenic and increased susceptibility to arsenic-caused cancer. In these studies, methylation patterns were based on a single assessment of urinary arsenic metabolites collected at the time of cancer diagnosis. However, the latency of arsenic-caused cancer may be several decades, and the extent to which a recent measurement can be used to estimate a person's past methylation pattern is unknown. In this investigation, the distribution of urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate was used to assess intraindividual variation in methylation capacity in 81 subjects with low to moderate arsenic exposures. Multiple urine samples were collected from each subject over a 1-year period. Duplicate analyses done on 27 samples were used to assess laboratory measurement imprecision. The intraclass correlation coefficients (ICC) for the proportion of urinary arsenic as inorganic arsenic, monomethylarsonate, and dimethylarsinate in samples taken an average of 258 days apart, were 0.45 [95% confidence interval (95% CI), 0.23-0.63] 0.46 (95% CI, 0.24-0.64), and 0.49 (95% CI, 0.28-0.66). In analyses of duplicate samples, ICCs for the concentration of arsenic species ranged from 0.87 to 0.93, whereas ICCs for species proportions ranged from 0.63 to 0.76. These data suggest that individual methylation patterns remain fairly stable over time, although variability due to measurement imprecision or intraindividual changes over time does occur. This variability could lead to misclassification of methylation patterns and could bias relative risk estimates in studies of methylation and cancer towards the null.","Intraindividual variability in arsenic methylation in a US populationAbs: Several recent investigations have reported associations between a reduced capacity to fully methylate inorganic arsenic and increased susceptibility to arsenic-caused cancer. In these studies, methylation patterns were based on a single assessment of urinary arsenic metabolites collected at the time of cancer diagnosis. However, the latency of arsenic-caused cancer may be several decades, and the extent to which a recent measurement can be used to estimate a person's past methylation pattern is unknown. In this investigation, the distribution of urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate was used to assess intraindividual variation in methylation capacity in 81 subjects with low to moderate arsenic exposures. Multiple urine samples were collected from each subject over a 1-year period. Duplicate analyses done on 27 samples were used to assess laboratory measurement imprecision. The intraclass correlation coefficients (ICC) for the proportion of urinary arsenic as inorganic arsenic, monomethylarsonate, and dimethylarsinate in samples taken an average of 258 days apart, were 0.45 [95% confidence interval (95% CI), 0.23-0.63] 0.46 (95% CI, 0.24-0.64), and 0.49 (95% CI, 0.28-0.66). In analyses of duplicate samples, ICCs for the concentration of arsenic species ranged from 0.87 to 0.93, whereas ICCs for species proportions ranged from 0.63 to 0.76. These data suggest that individual methylation patterns remain fairly stable over time, although variability due to measurement imprecision or intraindividual changes over time does occur. This variability could lead to misclassification of methylation patterns and could bias relative risk estimates in studies of methylation and cancer towards the null."
270,Szakova et al. 2009,Influence of elevated content of cadmium and arsenic in diet containing feeding yeast on organisms of rats," The influence of elevated cadmium content in diet on the content of this element in liver, kidney and testes of 68 male rats was studied in dependence on the chemical form of applied cadmium (as inorganic salt - CdCl2 and organically bound in yeast cells); the influence of elevated arsenic content (as NaAsO2) in diet on its content in the same organs was also investigated. The interactions between arsenic and cadmium in the above-mentioned organs were studied. The addition of cadmium to the diet of rats significantly (P < 0.05) increased cadmium content in several organs. The addition of yeast containing the natural level of Cd increased the content of cadmium in liver and kidney of experimental animals significantly (P < 0.05). A significantly (P < 0.05) increased cadmium accumulation in organs was observed after the addition of Cd as CdCl2, compared with the addition of Cd as organically bound Cd in yeast cells. At the same time, the addition of yeasts containing the natural level of Cd decreased the Cd accumulation applied as CdCl2 in the examined organs. The addition of sodium arsenite to the diet of rats led to a significantly (P < 0.05) increased arsenic content in all the analyzed organs. The addition of yeasts to the diet increased arsenic content in liver and at the same time suppressed its content in kidneys of experimental animals. The interaction between arsenic and cadmium applied simultaneously was evident. The addition of As to the diet decreased the accumulation of Cd in kidney and increased its accumulation in testes. The addition of Cd to the diet increased arsenic content in liver and kidney and decreased its content in testes.","Influence of elevated content of cadmium and arsenic in diet containing feeding yeast on organisms of ratsAbs: The influence of elevated cadmium content in diet on the content of this element in liver, kidney and testes of 68 male rats was studied in dependence on the chemical form of applied cadmium (as inorganic salt - CdCl2 and organically bound in yeast cells); the influence of elevated arsenic content (as NaAsO2) in diet on its content in the same organs was also investigated. The interactions between arsenic and cadmium in the above-mentioned organs were studied. The addition of cadmium to the diet of rats significantly (P < 0.05) increased cadmium content in several organs. The addition of yeast containing the natural level of Cd increased the content of cadmium in liver and kidney of experimental animals significantly (P < 0.05). A significantly (P < 0.05) increased cadmium accumulation in organs was observed after the addition of Cd as CdCl2, compared with the addition of Cd as organically bound Cd in yeast cells. At the same time, the addition of yeasts containing the natural level of Cd decreased the Cd accumulation applied as CdCl2 in the examined organs. The addition of sodium arsenite to the diet of rats led to a significantly (P < 0.05) increased arsenic content in all the analyzed organs. The addition of yeasts to the diet increased arsenic content in liver and at the same time suppressed its content in kidneys of experimental animals. The interaction between arsenic and cadmium applied simultaneously was evident. The addition of As to the diet decreased the accumulation of Cd in kidney and increased its accumulation in testes. The addition of Cd to the diet increased arsenic content in liver and kidney and decreased its content in testes."
271,Theegala et al. 2007,Toxicity and biouptake of lead and arsenic by Daphnia pulex," Acute and chronic toxicity studies were conducted on Daphnia pulex using synthetic lead and arsenic water samples. For acute studies, solutions with 0.25, 0.5, 1.0, 2.0, 5.0 mg/L lead and arsenic along with a control were used. The chronic studies were conducted for 21 days using 0.25, 0.5, 1.0 mg/L lead and arsenic solutions along with a control. Results indicated that the LC50 (48 hour) was 4.0 and 3.4 mg/L for lead and arsenic, respectively. Results from chronic studies suggest that the exposure to lead solutions significantly (P < 0.05) impaired the reproduction rates of Daphnia at the 1 mg/L concentration. However, the reproduction rates were enhanced at low concentrations of arsenic (up to 0.5 mg/L). A second chronic study was conducted to confirm this finding. Results from the second study indicated that lead exhibited significantly higher (P < 0.05) toxicity at 0.5 mg/L concentration, while reproduction rates in all concentrations of arsenic solutions were not significantly different from the controls. Metal analysis on exposed Daphnia, following nitric acid digestion procedures, indicated that Daphnia bio-accumulated 75.3 - 97.2% of the lead added to the experimental containers. This high lead biouptake coupled with the fast growth, high reproduction rates, and short life cycle all suggest that a Daphnia-based remediation (growth and partial harvest) may a viable treatment alternative that is worth considering. However, further field studies have to be conducted to verify this alternative. Biouptake or sequestration by Daphnia of arsenic at all tested concentrations was negligible, thereby, suggesting selective uptake or sequestration by daphnia under the tested pH and temperature conditions.","Toxicity and biouptake of lead and arsenic by Daphnia pulexAbs: Acute and chronic toxicity studies were conducted on Daphnia pulex using synthetic lead and arsenic water samples. For acute studies, solutions with 0.25, 0.5, 1.0, 2.0, 5.0 mg/L lead and arsenic along with a control were used. The chronic studies were conducted for 21 days using 0.25, 0.5, 1.0 mg/L lead and arsenic solutions along with a control. Results indicated that the LC50 (48 hour) was 4.0 and 3.4 mg/L for lead and arsenic, respectively. Results from chronic studies suggest that the exposure to lead solutions significantly (P < 0.05) impaired the reproduction rates of Daphnia at the 1 mg/L concentration. However, the reproduction rates were enhanced at low concentrations of arsenic (up to 0.5 mg/L). A second chronic study was conducted to confirm this finding. Results from the second study indicated that lead exhibited significantly higher (P < 0.05) toxicity at 0.5 mg/L concentration, while reproduction rates in all concentrations of arsenic solutions were not significantly different from the controls. Metal analysis on exposed Daphnia, following nitric acid digestion procedures, indicated that Daphnia bio-accumulated 75.3 - 97.2% of the lead added to the experimental containers. This high lead biouptake coupled with the fast growth, high reproduction rates, and short life cycle all suggest that a Daphnia-based remediation (growth and partial harvest) may a viable treatment alternative that is worth considering. However, further field studies have to be conducted to verify this alternative. Biouptake or sequestration by Daphnia of arsenic at all tested concentrations was negligible, thereby, suggesting selective uptake or sequestration by daphnia under the tested pH and temperature conditions."
272,Thornton et al. 2009,The production of speiss (iron arsenide) during the Early Bronze Age in Iran," In this paper, analyses of some unusual slag samples from the prehistoric site of Tepe Hissar in north-eastern Iran are presented. These slags are the remains of a five-thousand-year-old pyrotechnological process that produced speiss, a quasi-metallic material usually formed as an accidental by-product of copper or lead smelting. We argue that the ""speiss slags"" from Tepe Hissar suggest the intentional production of iron-arsenic alloy (""speiss"") in prehistory. Why the Tepe Hissar metalworkers produced speiss is a question that requires further investigation, but our preliminary assessment suggests that it was to provide arsenic as an alloying component for arsenical copper, the preferred copper alloy during much of the Early Bronze Age in Iran. and widely used across the ancient world. This recognition significantly advances our understanding of the early stages of metallurgy in the Old World. (C) 2008 Elsevier Ltd. All rights reserved.","The production of speiss (iron arsenide) during the Early Bronze Age in IranAbs: In this paper, analyses of some unusual slag samples from the prehistoric site of Tepe Hissar in north-eastern Iran are presented. These slags are the remains of a five-thousand-year-old pyrotechnological process that produced speiss, a quasi-metallic material usually formed as an accidental by-product of copper or lead smelting. We argue that the ""speiss slags"" from Tepe Hissar suggest the intentional production of iron-arsenic alloy (""speiss"") in prehistory. Why the Tepe Hissar metalworkers produced speiss is a question that requires further investigation, but our preliminary assessment suggests that it was to provide arsenic as an alloying component for arsenical copper, the preferred copper alloy during much of the Early Bronze Age in Iran. and widely used across the ancient world. This recognition significantly advances our understanding of the early stages of metallurgy in the Old World. (C) 2008 Elsevier Ltd. All rights reserved."
273,Trejo-Acevedo et al. 2009,Exposure assessment of persistent organic pollutants and metals in Mexican children," Environmental policies in Mexico have contributed to the reduction in the production or use of some persistent organic pollutants (POPs) and metals. How ever, monitoring of POPs concentrations in humans living in hot spots is lacking. Therefore, the objective of this study was to con duct a screening for POPs and metals first in Mexican children living in high-risk areas. During the year 2004, we analyzed a total of 229 healthy children (aged 6-12 years old) who resided in communi ties located in nine Mexican states. Organochlorine insecticides, PCBs and metals were quantified in plasma and urine samples. We detected p'p-DDE in all the children; more over, p'p-DDT, lindane and hexa chloro benzene were detected respectively in 14%, 85% and 10% of the children studied. Mea sur able levels of PCBs were recorded in only one community, where six of 14 PCB congeners assayed were detected (numbers 52, 118, 138, 153, 170 and 180). All the children had detect able levels of lead in their blood (mean level, 4.6 mu g dL(-1)); further more, 57% of the children studied had levels higher than 5.0 mu g/dL. The mean level of urinary arsenic (UAs) for all the children was 22.35 mu g g(-1) creatinine and 15% of those children had concentrations of UAs above 50 mu g g(-1) creatinine. For cadmium, the mean urinary level was 0.78 mu g g(-1) creatinine, and only one percent of the children had values above 2.0 mu g g(-1) creatinine. The results can not be generalized since the communi ties selected are not representative of the Mexican population; how ever, they indicate that Mexican children are exposed to chemicals and some at risk levels. (C) 2008 Elsevier Ltd. All rights reserved.","Exposure assessment of persistent organic pollutants and metals in Mexican childrenAbs: Environmental policies in Mexico have contributed to the reduction in the production or use of some persistent organic pollutants (POPs) and metals. How ever, monitoring of POPs concentrations in humans living in hot spots is lacking. Therefore, the objective of this study was to con duct a screening for POPs and metals first in Mexican children living in high-risk areas. During the year 2004, we analyzed a total of 229 healthy children (aged 6-12 years old) who resided in communi ties located in nine Mexican states. Organochlorine insecticides, PCBs and metals were quantified in plasma and urine samples. We detected p'p-DDE in all the children; more over, p'p-DDT, lindane and hexa chloro benzene were detected respectively in 14%, 85% and 10% of the children studied. Mea sur able levels of PCBs were recorded in only one community, where six of 14 PCB congeners assayed were detected (numbers 52, 118, 138, 153, 170 and 180). All the children had detect able levels of lead in their blood (mean level, 4.6 mu g dL(-1)); further more, 57% of the children studied had levels higher than 5.0 mu g/dL. The mean level of urinary arsenic (UAs) for all the children was 22.35 mu g g(-1) creatinine and 15% of those children had concentrations of UAs above 50 mu g g(-1) creatinine. For cadmium, the mean urinary level was 0.78 mu g g(-1) creatinine, and only one percent of the children had values above 2.0 mu g g(-1) creatinine. The results can not be generalized since the communi ties selected are not representative of the Mexican population; how ever, they indicate that Mexican children are exposed to chemicals and some at risk levels. (C) 2008 Elsevier Ltd. All rights reserved."
274,Veeramachaneni 2008,Impact of environmental pollutants on the male: Effects on germ cell differentiation," A variety of so-called innocuous chemicals can have insidious and long lasting effects on the developing male reproductive system. Developmental exposures of male rabbits to common industrial contaminants in drinking water (a mixture of arsenic, chromium, lead, benzene, chloroform, phenol, and trichloroethylene); alkyl phenols (e.g. octylphenol); water disinfection by-products (e.g. dibromoacetic acid); anti-androgenic pesticides (e.g. pp'-DDT and vinclozolin); and plasticizers (e.g. dibutyl phthalate) produce testicular dysgenesis. The lesions include testicular carcinoma in situ, also called intratubular germ cell neoplasia - the precursor lesion of germ cell tumors in men, and acrosomal dysgenesis - characterized by sharing of a dysplastic acrosome by two or more spermatids resulting in characteristic sperm acrosomal-nuclear malformations. Certain manifestations of testicular dysgenesis arch across environmental agents, and sequelae of intentional developmental exposures of rabbits duplicate what has been encountered in deer, horses, and humans for which the etiology is uncertain. (C) 2007 Elsevier B.V. All rights reserved.","Impact of environmental pollutants on the male: Effects on germ cell differentiationAbs: A variety of so-called innocuous chemicals can have insidious and long lasting effects on the developing male reproductive system. Developmental exposures of male rabbits to common industrial contaminants in drinking water (a mixture of arsenic, chromium, lead, benzene, chloroform, phenol, and trichloroethylene); alkyl phenols (e.g. octylphenol); water disinfection by-products (e.g. dibromoacetic acid); anti-androgenic pesticides (e.g. pp'-DDT and vinclozolin); and plasticizers (e.g. dibutyl phthalate) produce testicular dysgenesis. The lesions include testicular carcinoma in situ, also called intratubular germ cell neoplasia - the precursor lesion of germ cell tumors in men, and acrosomal dysgenesis - characterized by sharing of a dysplastic acrosome by two or more spermatids resulting in characteristic sperm acrosomal-nuclear malformations. Certain manifestations of testicular dysgenesis arch across environmental agents, and sequelae of intentional developmental exposures of rabbits duplicate what has been encountered in deer, horses, and humans for which the etiology is uncertain. (C) 2007 Elsevier B.V. All rights reserved."
275,von Ehrenstein et al. 2007,Children's intellectual function in relation to arsenic exposure," Background: Very little evidence exists concerning the possible impairment of children's intellectual function in relation to arsenic exposure in utero and during childhood. Methods: We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001-2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates. Results: Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, -0.14, -0.28; P for trend = 0.02), the object assembly test (0, -0.16, -0.24- P for trend = 0.03), and the picture completion test (0, - 0.15, -0.26; P for trend = 0.02). These findings correspond to relative declines of 12% (95% confidence interval =0.4% to 24%) in the vocabulary test, 21% (-0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood. Conclusions: Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in school-aged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function.","Children's intellectual function in relation to arsenic exposureAbs: Background: Very little evidence exists concerning the possible impairment of children's intellectual function in relation to arsenic exposure in utero and during childhood. Methods: We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001-2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates. Results: Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, -0.14, -0.28; P for trend = 0.02), the object assembly test (0, -0.16, -0.24- P for trend = 0.03), and the picture completion test (0, - 0.15, -0.26; P for trend = 0.02). These findings correspond to relative declines of 12% (95% confidence interval =0.4% to 24%) in the vocabulary test, 21% (-0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood. Conclusions: Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in school-aged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function."
276,Wasserman et al. 2007,"Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh"," BACKGROUND: We recently reported results of a cross-sectional investigation of intellectual function in 10-year-olds in Bangladesh, who had been exposed to arsenic from drinking water in their home wells. OBJECTIVES: We present results of a similar investigation of 301 randomly selected 6-year-olds whose parents participated in our ongoing prospective study of the health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. METHODS: Water As and manganese concentrations of tube wells at each home were obtained by surveying all study region wells. Children and mothers were first visited at home, where the quality of home stimulation was measured, and then seen in our field clinic, where children received a medical examination wherein weight, height, and head circumference were assessed. We assessed children's intellectual function using subtests drawn from the Wechsler Preschool and Primary Scale of Intelligence, version III, by summing weighted items across domains to create Verbal, Performance, Processing Speed, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and were asked to provide blood samples for blood lead measurements. RESULTS: Exposure to As from drinking water was associated with reduced intellectual function before and after adjusting for water Mn, for blood lead levels, and for sociodemographic features known to contribute to intellectual function. With covariate adjustment, water As remained significantly negatively associated with both Performance and Processing Speed raw scores; associations were less strong than in our previously studied 10-year-olds. CONCLUSION: This second cross-sectional study of As exposure expands our concerns about As neurotoxicity to a younger age group.","Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, BangladeshAbs: BACKGROUND: We recently reported results of a cross-sectional investigation of intellectual function in 10-year-olds in Bangladesh, who had been exposed to arsenic from drinking water in their home wells. OBJECTIVES: We present results of a similar investigation of 301 randomly selected 6-year-olds whose parents participated in our ongoing prospective study of the health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. METHODS: Water As and manganese concentrations of tube wells at each home were obtained by surveying all study region wells. Children and mothers were first visited at home, where the quality of home stimulation was measured, and then seen in our field clinic, where children received a medical examination wherein weight, height, and head circumference were assessed. We assessed children's intellectual function using subtests drawn from the Wechsler Preschool and Primary Scale of Intelligence, version III, by summing weighted items across domains to create Verbal, Performance, Processing Speed, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and were asked to provide blood samples for blood lead measurements. RESULTS: Exposure to As from drinking water was associated with reduced intellectual function before and after adjusting for water Mn, for blood lead levels, and for sociodemographic features known to contribute to intellectual function. With covariate adjustment, water As remained significantly negatively associated with both Performance and Processing Speed raw scores; associations were less strong than in our previously studied 10-year-olds. CONCLUSION: This second cross-sectional study of As exposure expands our concerns about As neurotoxicity to a younger age group."
277,Wong et al. 2005,Increased levels of 8-hydroxy-2 '-deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren," Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean SE, 16.0 +/- 1.3; VS. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, P = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children.","Increased levels of 8-hydroxy-2 '-deoxyguanosine attributable to carcinogenic metal exposure among schoolchildrenAbs: Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean SE, 16.0 +/- 1.3; VS. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, P = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children."
278,Zhai et al. 2005,Proteomic profiling in the sera of workers occupationally exposed to arsenic and lead: identification of potential biomarkers," Arsenic (As) and lead (Pb) are important inorganic toxicants in the environment. Frequently, humans are exposed to the mixtures of As and Pb, but little is known about the expression of biomarkers resulting from such mixed exposures. In this study, we analyzed serum proteomic profiles in a group of smelter workers with the aim of identifying protein biomarkers of mixed As and Pb exposure. Forty-six male workers co-exposed to As and Pb were studied. Forty-five age-matched male office workers were chosen as controls. Urine As and blood Pb concentrations were determined. Serum proteomic profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight (SELDI-TOF) mass spectrometer on the WCX2 ProteinChip. Using Recursive support vector machine (RSVM) algorithm, a panel of five peptides/proteins (2097 Da, 2953 Da, 3941 Da, 5338 Da, and 5639 Da) was selected based on their collective contribution to the optional separation between higher metal mixture exposure and non-exposure controls. Among these five selected markers, the 3941 Da was down-regulated and the four other proteins were up-regulated. Descriptive statistics confirmed that these five proteins differed significantly between metal exposure and non-exposure. Interestingly, the combined use of the five selected biomarkers could achieve higher discriminative power than single marker. These results demonstrated that proteomic technology, in conjunction with bioinformatics tools, could facilitate the discovery of new and better biomarkers of mixed metal exposure.","Proteomic profiling in the sera of workers occupationally exposed to arsenic and lead: identification of potential biomarkersAbs: Arsenic (As) and lead (Pb) are important inorganic toxicants in the environment. Frequently, humans are exposed to the mixtures of As and Pb, but little is known about the expression of biomarkers resulting from such mixed exposures. In this study, we analyzed serum proteomic profiles in a group of smelter workers with the aim of identifying protein biomarkers of mixed As and Pb exposure. Forty-six male workers co-exposed to As and Pb were studied. Forty-five age-matched male office workers were chosen as controls. Urine As and blood Pb concentrations were determined. Serum proteomic profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight (SELDI-TOF) mass spectrometer on the WCX2 ProteinChip. Using Recursive support vector machine (RSVM) algorithm, a panel of five peptides/proteins (2097 Da, 2953 Da, 3941 Da, 5338 Da, and 5639 Da) was selected based on their collective contribution to the optional separation between higher metal mixture exposure and non-exposure controls. Among these five selected markers, the 3941 Da was down-regulated and the four other proteins were up-regulated. Descriptive statistics confirmed that these five proteins differed significantly between metal exposure and non-exposure. Interestingly, the combined use of the five selected biomarkers could achieve higher discriminative power than single marker. These results demonstrated that proteomic technology, in conjunction with bioinformatics tools, could facilitate the discovery of new and better biomarkers of mixed metal exposure."
279,Zhang et al. 2009,"Health risks from arsenic-contaminated soil in Flin Flon-Creighton, Canada: Integrating geostatistical simulation and dose-response model"," Elevated concentrations of arsenic were detected in surface soils adjacent to a smelting complex in northern Canada. We evaluated the cancer risks caused by exposure to arsenic in two communities through combining geostatistical simulation with demographic data and dose-response models in a framework. Distribution of arsenic was first estimated using geostatistical circulant-embedding simulation method. We then evaluated the exposures from inadvertent ingestion, inhalation and dermal contact. Risks of skin caner and three internal cancers were estimated at both grid scale and census-unit scale using parametric dose-response models. Results indicated that local residents could face non-negligible cancer risks (skin cancer and liver cancer mainly). Uncertainties of risk estimates were discussed from the aspects of arsenic concentrations, exposed population and dose-response model. Reducing uncertainties would require additional soil sampling, epidemic records as well as complementary studies on land use, demographic variation, outdoor activities and bioavailability of arsenic. (c) 2009 Elsevier Ltd. All rights reserved.","Health risks from arsenic-contaminated soil in Flin Flon-Creighton, Canada: Integrating geostatistical simulation and dose-response modelAbs: Elevated concentrations of arsenic were detected in surface soils adjacent to a smelting complex in northern Canada. We evaluated the cancer risks caused by exposure to arsenic in two communities through combining geostatistical simulation with demographic data and dose-response models in a framework. Distribution of arsenic was first estimated using geostatistical circulant-embedding simulation method. We then evaluated the exposures from inadvertent ingestion, inhalation and dermal contact. Risks of skin caner and three internal cancers were estimated at both grid scale and census-unit scale using parametric dose-response models. Results indicated that local residents could face non-negligible cancer risks (skin cancer and liver cancer mainly). Uncertainties of risk estimates were discussed from the aspects of arsenic concentrations, exposed population and dose-response model. Reducing uncertainties would require additional soil sampling, epidemic records as well as complementary studies on land use, demographic variation, outdoor activities and bioavailability of arsenic. (c) 2009 Elsevier Ltd. All rights reserved."
280,Hwang et al. 2009,The association between low levels of lead in blood and occupational noise-induced hearing loss in steel workers," Abstract: As the use of leaded gasoline has ceased in the last decade, background lead exposure has generally been reduced. The aim of this study was to examine the effect of low-level lead exposure on human hearing loss. This study was conducted in a steel plant and 412 workers were recruited from all over the plant. Personal information such as demographics and work history was obtained through a questionnaire. All subjects took part in an audiometric examination of hearing thresholds, for both ears, with air-conducted pure tones at frequencies of 500, 1000, 2000, 3000, 4000, 6000 and 8000Hz. Subjects'' blood samples were collected and analyzed for levels of manganese, copper, zinc, arsenic, cadmium and lead with inductive couple plasma-mass spectrometry. Meanwhile, noise levels in different working zones were determined using a sound level meter with A-weighting network. Only subjects with hearing loss difference of no more than 15dB between both ears and had no congenital abnormalities were included in further data analysis. Lead was the only metal in blood found significantly correlated with hearing loss for most tested sound frequencies (p <0.05 to p <0.0001). After adjustment for age and noise level, the logistic regression model analysis indicated that elevated blood lead over 7ÃŽÂ¼g/dL was significantly associated with hearing loss at the sound frequencies of 3000 through 8000Hz with odds ratios raging from 3.06 to 6.26 (p <0.05~ p <0.005). We concluded that elevated blood lead at level below 10ÃŽÂ¼g/dL might enhance the noise-induced hearing loss. Future research needs to further explore the detailed mechanism. [Copyright &y& Elsevier]; Copyright of Science of the Total Environment is the property of Elsevier Science Publishers B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)","The association between low levels of lead in blood and occupational noise-induced hearing loss in steel workersAbs: Abstract: As the use of leaded gasoline has ceased in the last decade, background lead exposure has generally been reduced. The aim of this study was to examine the effect of low-level lead exposure on human hearing loss. This study was conducted in a steel plant and 412 workers were recruited from all over the plant. Personal information such as demographics and work history was obtained through a questionnaire. All subjects took part in an audiometric examination of hearing thresholds, for both ears, with air-conducted pure tones at frequencies of 500, 1000, 2000, 3000, 4000, 6000 and 8000Hz. Subjects'' blood samples were collected and analyzed for levels of manganese, copper, zinc, arsenic, cadmium and lead with inductive couple plasma-mass spectrometry. Meanwhile, noise levels in different working zones were determined using a sound level meter with A-weighting network. Only subjects with hearing loss difference of no more than 15dB between both ears and had no congenital abnormalities were included in further data analysis. Lead was the only metal in blood found significantly correlated with hearing loss for most tested sound frequencies (p <0.05 to p <0.0001). After adjustment for age and noise level, the logistic regression model analysis indicated that elevated blood lead over 7ÃŽÂ¼g/dL was significantly associated with hearing loss at the sound frequencies of 3000 through 8000Hz with odds ratios raging from 3.06 to 6.26 (p <0.05~ p <0.005). We concluded that elevated blood lead at level below 10ÃŽÂ¼g/dL might enhance the noise-induced hearing loss. Future research needs to further explore the detailed mechanism. [Copyright &y& Elsevier]; Copyright of Science of the Total Environment is the property of Elsevier Science Publishers B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)"
281,Jasso-Pineda et al. 2007,An Integrated Health Risk Assessment Approach to the Study of Mining Sites Contaminated with Arsenic and Lead," In order to test the value of an integrated approach for the analysis of health risks at contaminated sites, an integrated health risk assessment in a mining area was performed following 3 steps: 1) Environmental monitoring of surface soil, 2) assessment of exposure to metals in children and native rodents, and 3) DNA damage evaluation (comet assay) in children and rodents. These aspects also were studied in less exposed populations. Our results in humans showed that children living in the most polluted area (Villa de la Paz, Mexico) had higher lead blood concentrations (geometric mean of 13.8 mu g/dL) and urinary arsenic levels (geometric mean of 52.1 mu g/g creatinine) compared to children living in a control area (Matehuala, Mexico; blood lead of 7.3 mu g/dL; urinary arsenic of 16.8 mu g/g creatinine). Furthermore, the exposed children also had increased DNA damage (tail moment mean in Villa de la Paz of 4.8 vs 3.9 in Matehuala; p < 0.05). Results in rodents were identical. Animals captured in the polluted area had higher levels of arsenic (geometric mean of 1.3 mu g/g in liver and 1.8 mu g/g in kidney), lead (0.2 mu g/g in liver and 0.9 mu g/g in kidney), and cadmium (0.8 mu g/g in liver and 2.2 mu g/g in kidney), and increased DNA damage (tail moment mean of 18.2) when compared to control animals (arsenic in liver of 0.08 mu g/g and kidney of 0.1 mu g/g; lead in liver of 0.06 mu g/g and kidney of 0.3 mu g/g; cadmium in liver of 0.06 mu g/g and kidney of 0.6 mu g/g; and tail moment of 14.2). With the data in children and rodents, the weight-of-evidence for health risks (in this case DNA damage) associated with metal exposure in Villa de la Paz was strengthened. Therefore, a remediation program was easier to justify, and a feasibility study at this site is under way.","An Integrated Health Risk Assessment Approach to the Study of Mining Sites Contaminated with Arsenic and LeadAbs: In order to test the value of an integrated approach for the analysis of health risks at contaminated sites, an integrated health risk assessment in a mining area was performed following 3 steps: 1) Environmental monitoring of surface soil, 2) assessment of exposure to metals in children and native rodents, and 3) DNA damage evaluation (comet assay) in children and rodents. These aspects also were studied in less exposed populations. Our results in humans showed that children living in the most polluted area (Villa de la Paz, Mexico) had higher lead blood concentrations (geometric mean of 13.8 mu g/dL) and urinary arsenic levels (geometric mean of 52.1 mu g/g creatinine) compared to children living in a control area (Matehuala, Mexico; blood lead of 7.3 mu g/dL; urinary arsenic of 16.8 mu g/g creatinine). Furthermore, the exposed children also had increased DNA damage (tail moment mean in Villa de la Paz of 4.8 vs 3.9 in Matehuala; p < 0.05). Results in rodents were identical. Animals captured in the polluted area had higher levels of arsenic (geometric mean of 1.3 mu g/g in liver and 1.8 mu g/g in kidney), lead (0.2 mu g/g in liver and 0.9 mu g/g in kidney), and cadmium (0.8 mu g/g in liver and 2.2 mu g/g in kidney), and increased DNA damage (tail moment mean of 18.2) when compared to control animals (arsenic in liver of 0.08 mu g/g and kidney of 0.1 mu g/g; lead in liver of 0.06 mu g/g and kidney of 0.3 mu g/g; cadmium in liver of 0.06 mu g/g and kidney of 0.6 mu g/g; and tail moment of 14.2). With the data in children and rodents, the weight-of-evidence for health risks (in this case DNA damage) associated with metal exposure in Villa de la Paz was strengthened. Therefore, a remediation program was easier to justify, and a feasibility study at this site is under way."
282,Bardullas et al. 2009,"Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice"," Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.","Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in miceAbs: Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain."
283,Carpenter and Nevin 2010,Environmental causes of violence," Violent and anti-social behavior is usually attributed to social factors, including poverty, poor education, and family instability. There is also evidence that many forms of violent behavior are more frequent in individuals of lower IQ. The role of exposure to environmental contaminants has received little attention as a factor predisposing to violent behavior. However a number of environmental exposures are documented to result in a common pattern of neurobehavioral effects, including lowered IQ, shortened attention span, and increased frequency of antisocial behavior. This pattern is best described for children exposed to lead early in life, but a similar pattern is seen upon exposure to polychlorinated biphenyls and methyl mercury. Although not as extensively studied, similar decrements in IQ are seen upon exposure to arsenic and secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also associated with increased rates of conduct disorder and attention deficit hyperactivity. Recent evidence suggests that temporal trends in rates of violent crime in many nations are consistent with earlier preschool blood lead trends, with a lag of about 20Â years. These ecologic correlations are consistent with many controlled studies suggesting that lead-exposed children suffer irreversible brain alterations that make them more likely to commit violent crimes as young adults. If this pattern is true for lead and other contaminants, the most effective way to fight crime may be to prevent exposure to these contaminants.","Environmental causes of violenceAbs: Violent and anti-social behavior is usually attributed to social factors, including poverty, poor education, and family instability. There is also evidence that many forms of violent behavior are more frequent in individuals of lower IQ. The role of exposure to environmental contaminants has received little attention as a factor predisposing to violent behavior. However a number of environmental exposures are documented to result in a common pattern of neurobehavioral effects, including lowered IQ, shortened attention span, and increased frequency of antisocial behavior. This pattern is best described for children exposed to lead early in life, but a similar pattern is seen upon exposure to polychlorinated biphenyls and methyl mercury. Although not as extensively studied, similar decrements in IQ are seen upon exposure to arsenic and secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also associated with increased rates of conduct disorder and attention deficit hyperactivity. Recent evidence suggests that temporal trends in rates of violent crime in many nations are consistent with earlier preschool blood lead trends, with a lag of about 20Â years. These ecologic correlations are consistent with many controlled studies suggesting that lead-exposed children suffer irreversible brain alterations that make them more likely to commit violent crimes as young adults. If this pattern is true for lead and other contaminants, the most effective way to fight crime may be to prevent exposure to these contaminants."
284,Meno et al. 2009,Exposure to monomethylarsonous acid (MMAIII) leads to altered selenoprotein synthesis in a primary human lung cell model," Monomethylarsonous acid (MMAIII), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMAIII is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMAIII on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMAIII resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMAIII treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMAIII, as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMAIII induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMAIII alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.","Exposure to monomethylarsonous acid (MMAIII) leads to altered selenoprotein synthesis in a primary human lung cell modelAbs: Monomethylarsonous acid (MMAIII), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMAIII is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMAIII on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMAIII resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMAIII treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMAIII, as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMAIII induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMAIII alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element."
285,Rocha-Amador et al. 2009,Use of the Rey-Osterrieth Complex Figure Test for neurotoxicity evaluation of mixtures in children," The aim of this study was to assess the value of the children's version of the Rey-Osterrieth Complex Figure Test as a screening test in a population exposed to different mixtures of neurotoxicants. Copy and Immediate Recall scores were evaluated through the test. Children were recruited from three sites; an area with natural contamination by fluoride and arsenic (F-As), a mining-metallurgical area with lead and arsenic contamination (Pb-As) and a malaria zone with the evidence of fish contaminated with dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). Children aged 6-11 years old, living in one of the three polluted sites since birth were recruited (n = 166). The exposure was evaluated as follows: fluoride and arsenic in urine, lead in blood and DDT, dichlorodiphenyldichloroethylene (DDE) and PCBs in serum. To evaluate the test performance, z-scores for Copy and Immediate Recall were calculated. The proportion of children by residence area with performance lower than expected by age (below -1 SD) for Copy and Immediate Recall was in the F-As area (88.7% and 59%) and in the DDT-PCBs area (73% and 43.8%), respectively. In the Pb-As area, the proportion was 62% for both tests. After adjustment, Copy correlated inversely with fluoride in urine (r = -0.29; p < 0.001) and Immediate Recall correlated inversely with fluoride in urine (r = -0.27; p < 0.05), lead in blood (r = -0.72; p < 0.01), arsenic in urine (r = -0.63; p < 0.05) and DDE (r = -0.25; p < 0.05). This study provided evidence that children included in this research are living in high risk areas and were exposed to neurotoxicants. Poor performance in the test could be explained in some way by F, Pb, As or DDE exposure, however social factors or the low quality of school education prevalent in the areas could be playing an important role.","Use of the Rey-Osterrieth Complex Figure Test for neurotoxicity evaluation of mixtures in childrenAbs: The aim of this study was to assess the value of the children's version of the Rey-Osterrieth Complex Figure Test as a screening test in a population exposed to different mixtures of neurotoxicants. Copy and Immediate Recall scores were evaluated through the test. Children were recruited from three sites; an area with natural contamination by fluoride and arsenic (F-As), a mining-metallurgical area with lead and arsenic contamination (Pb-As) and a malaria zone with the evidence of fish contaminated with dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). Children aged 6-11 years old, living in one of the three polluted sites since birth were recruited (n = 166). The exposure was evaluated as follows: fluoride and arsenic in urine, lead in blood and DDT, dichlorodiphenyldichloroethylene (DDE) and PCBs in serum. To evaluate the test performance, z-scores for Copy and Immediate Recall were calculated. The proportion of children by residence area with performance lower than expected by age (below -1 SD) for Copy and Immediate Recall was in the F-As area (88.7% and 59%) and in the DDT-PCBs area (73% and 43.8%), respectively. In the Pb-As area, the proportion was 62% for both tests. After adjustment, Copy correlated inversely with fluoride in urine (r = -0.29; p < 0.001) and Immediate Recall correlated inversely with fluoride in urine (r = -0.27; p < 0.05), lead in blood (r = -0.72; p < 0.01), arsenic in urine (r = -0.63; p < 0.05) and DDE (r = -0.25; p < 0.05). This study provided evidence that children included in this research are living in high risk areas and were exposed to neurotoxicants. Poor performance in the test could be explained in some way by F, Pb, As or DDE exposure, however social factors or the low quality of school education prevalent in the areas could be playing an important role."
286,Kerckaert et al. 1996,Use of the Syrian hamster embryo cell transformation assay for determining the carcinogenic potential of heavy metal compounds," Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, vanadium pentoxide, and nickel sulfate heptahydrate were tested in the Syrian hamster embryo (SHE) assay in order to increase the SHE assay database for heavy metals. All five compounds produced significant morphological transformation at one or more doses in a dose-responsive manner. Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, and nickel (II) sulfate heptahydrate were all positive with a 24-hr exposure, suggesting direct DNA perturbation. Vanadium pentoxide was negative with a 24-hr exposure, but positive with a 7-day exposure. This pattern of response (24-hr SHE negative/7-day SHE positive) has been seen with other chemicals which have tumor promotion-like characteristics. Since the inception of the use of the SHE cell transformation assay for detecting the neoplastic transformation potential of chemicals, over 42 heavy metal compounds have been tested in this assay. Based on the 24 metal compounds which have been tested in the SHE, Salmonella, and some type of rodent bioassay, the SHE assay is 92% concordant with rodent bioassay carcinogenicity results, including a sensitivity of 95% (21/22) and a specificity of 50% (1/2). At this time, the measure of SHE assay specificity for rodent carcinogenicity of metals is limited by the paucity of metal compounds which are rodent noncarcinogens. The Salmonella assay results are only 33% concordant with the rodent bioassay for these same chemicals. This relatively high concordance between the SHE assay and the rodent bioassay carcinogenicity results demonstrates the utility of the SHE assay for determining the carcinogenic potential of heavy metal compounds in rodent cancer bioassays.","Use of the Syrian hamster embryo cell transformation assay for determining the carcinogenic potential of heavy metal compoundsAbs: Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, vanadium pentoxide, and nickel sulfate heptahydrate were tested in the Syrian hamster embryo (SHE) assay in order to increase the SHE assay database for heavy metals. All five compounds produced significant morphological transformation at one or more doses in a dose-responsive manner. Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, and nickel (II) sulfate heptahydrate were all positive with a 24-hr exposure, suggesting direct DNA perturbation. Vanadium pentoxide was negative with a 24-hr exposure, but positive with a 7-day exposure. This pattern of response (24-hr SHE negative/7-day SHE positive) has been seen with other chemicals which have tumor promotion-like characteristics. Since the inception of the use of the SHE cell transformation assay for detecting the neoplastic transformation potential of chemicals, over 42 heavy metal compounds have been tested in this assay. Based on the 24 metal compounds which have been tested in the SHE, Salmonella, and some type of rodent bioassay, the SHE assay is 92% concordant with rodent bioassay carcinogenicity results, including a sensitivity of 95% (21/22) and a specificity of 50% (1/2). At this time, the measure of SHE assay specificity for rodent carcinogenicity of metals is limited by the paucity of metal compounds which are rodent noncarcinogens. The Salmonella assay results are only 33% concordant with the rodent bioassay for these same chemicals. This relatively high concordance between the SHE assay and the rodent bioassay carcinogenicity results demonstrates the utility of the SHE assay for determining the carcinogenic potential of heavy metal compounds in rodent cancer bioassays."
287,Aggarwal et al. 2009,Effects of subchronic coexposure to arsenic and endosulfan on the erythrocytes of broiler chickens: A biochemical study," Arsenic is a known global groundwater contaminant. The organochlorine insecticide endosulfan has gained significance as an environmental pollutant due to its widespread use in the control of many food- and non-food-crop-damaging insects. The adverse effects produced by arsenic or endosulfan alone in humans and animals are well documented, but very little is known about the consequences of their coexposure. We evaluated whether their simultaneous exposure can induce oxidative stress and affect antioxidative systems and certain membrane-bound enzymes in erythrocytes of broiler chickens. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water or 30 ppm of endosulfan-mixed feed or similarly coexposed to these in the same dose levels for 60 days. At term, the impact of their coexposure was assessed by evaluating lipid peroxidation (LPO), activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST), different ATPases and acetylcholinesterase (AChE) in erythrocytes, serum glucose, and levels of glutathione (GSH) and glycosylated hemoglobin (GHb) in blood. LPO was increased with all of the treatments. Catalase was decreased with endosulfan and the coexposure, but not with arsenic, whereas GSH was decreased with arsenic and endosulfan, but not with the coexposure. All of the treatments increased SOD and GPx activities. GST activity was increased only in the coexposed birds. None of the treatments affected the activities of total ATPase and Mg2+-ATPase. Na+-K+-ATPase activity was decreased in the endosulfan-treated and the coexposed birds. All three exposures increased erythrocyte AChE activity. Endosulfan increased the serum glucose level and arsenic and endosulfan increased GHb levels, but these were not altered in the coexposed birds. Erythrocyte protein content was insignificantly decreased with these treatments. Overall, the effects of coexposure were not appreciably different from either of the agents, except on AChE, GSH, and glucose. The results do not reflect any specific type of interaction between these agents in chicken erythrocytes, but they do indicate that the coexposure induces a low level of oxidative stress, which is comparable to that induced by arsenic or endosulfan.","Effects of subchronic coexposure to arsenic and endosulfan on the erythrocytes of broiler chickens: A biochemical studyAbs: Arsenic is a known global groundwater contaminant. The organochlorine insecticide endosulfan has gained significance as an environmental pollutant due to its widespread use in the control of many food- and non-food-crop-damaging insects. The adverse effects produced by arsenic or endosulfan alone in humans and animals are well documented, but very little is known about the consequences of their coexposure. We evaluated whether their simultaneous exposure can induce oxidative stress and affect antioxidative systems and certain membrane-bound enzymes in erythrocytes of broiler chickens. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water or 30 ppm of endosulfan-mixed feed or similarly coexposed to these in the same dose levels for 60 days. At term, the impact of their coexposure was assessed by evaluating lipid peroxidation (LPO), activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST), different ATPases and acetylcholinesterase (AChE) in erythrocytes, serum glucose, and levels of glutathione (GSH) and glycosylated hemoglobin (GHb) in blood. LPO was increased with all of the treatments. Catalase was decreased with endosulfan and the coexposure, but not with arsenic, whereas GSH was decreased with arsenic and endosulfan, but not with the coexposure. All of the treatments increased SOD and GPx activities. GST activity was increased only in the coexposed birds. None of the treatments affected the activities of total ATPase and Mg2+-ATPase. Na+-K+-ATPase activity was decreased in the endosulfan-treated and the coexposed birds. All three exposures increased erythrocyte AChE activity. Endosulfan increased the serum glucose level and arsenic and endosulfan increased GHb levels, but these were not altered in the coexposed birds. Erythrocyte protein content was insignificantly decreased with these treatments. Overall, the effects of coexposure were not appreciably different from either of the agents, except on AChE, GSH, and glucose. The results do not reflect any specific type of interaction between these agents in chicken erythrocytes, but they do indicate that the coexposure induces a low level of oxidative stress, which is comparable to that induced by arsenic or endosulfan."
288,Albert et al. 2008,"DOSE-DEPENDENT UPTAKE, ELIMINATION, AND TOXICITY OF MONOSODIUM METHANEARSONATE IN ADULT ZEBRA FINCHES (TAENIOPYGIA GUTTATA)"," Monosodium methanearsonate (MSMA), an arsenic-based pesticide, has been used for the past 10 years in attempts to suppress mountain pine beetle (Dendroctonus ponderosae) outbreaks in British Columbia, Canada. Previous studies have shown that cavity nesting forest birds such as woodpeckers forage and breed in MSMA treated pine stands. Here we examined the effects of MSMA in the laboratory using the zebra finch (Taeniopygia guttata), with the objective to examine tissue distribution and sublethal toxic effects in a model avian species. Zebra finches were exposed to this pesticide at doses similar to those found in bark beetle samples from MSMA stands of trees treated in the southern interior of British Columbia (8, 24, and 72 ÃŽÂ¼g/g/d and a control group). Results showed high excretion (>90%) of arsenic in all dose groups, as well as dose-dependent trends in accumulation of arsenic in the blood (p < 0.001) and specific tissues. Monomethylarsonic acid, MMA (V), was the predominant form of arsenic in the blood plasma. Dimethylarsinic acid was the major form of arsenic found in the liver (83%) and kidney (61%) tissues. The brain tissue contained primarily the MMA (V) form (57%). Significant weight loss occurred in the two highest dose groups (p < 0.05). Birds in the highest dose group lost up to 15% of initial body mass. ABSTRACT FROM AUTHOR Copyright of Environmental Toxicology & Chemistry is the property of Allen Press Publishing Services Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","DOSE-DEPENDENT UPTAKE, ELIMINATION, AND TOXICITY OF MONOSODIUM METHANEARSONATE IN ADULT ZEBRA FINCHES (TAENIOPYGIA GUTTATA)Abs: Monosodium methanearsonate (MSMA), an arsenic-based pesticide, has been used for the past 10 years in attempts to suppress mountain pine beetle (Dendroctonus ponderosae) outbreaks in British Columbia, Canada. Previous studies have shown that cavity nesting forest birds such as woodpeckers forage and breed in MSMA treated pine stands. Here we examined the effects of MSMA in the laboratory using the zebra finch (Taeniopygia guttata), with the objective to examine tissue distribution and sublethal toxic effects in a model avian species. Zebra finches were exposed to this pesticide at doses similar to those found in bark beetle samples from MSMA stands of trees treated in the southern interior of British Columbia (8, 24, and 72 ÃŽÂ¼g/g/d and a control group). Results showed high excretion (>90%) of arsenic in all dose groups, as well as dose-dependent trends in accumulation of arsenic in the blood (p < 0.001) and specific tissues. Monomethylarsonic acid, MMA (V), was the predominant form of arsenic in the blood plasma. Dimethylarsinic acid was the major form of arsenic found in the liver (83%) and kidney (61%) tissues. The brain tissue contained primarily the MMA (V) form (57%). Significant weight loss occurred in the two highest dose groups (p < 0.05). Birds in the highest dose group lost up to 15% of initial body mass. ABSTRACT FROM AUTHOR Copyright of Environmental Toxicology & Chemistry is the property of Allen Press Publishing Services Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
289,Chang et al. 2008,The ars genotype characterization of arsenic-resistant bacteria from arsenic-contaminated gold-silver mines in the Republic of Korea," The isolates were identified on the basis of ars genotype characteristics as well as arsenic oxidation/reduction analysis based on the molecular detection characterization. Diversity, pH range (4.0 to 7.0), location, and ars features were assessed for four arsenic-contaminated pond sites and six arsenic tailings located in the Duck-um mine and Myoung-bong mine areas. The presence of ars genes in the genomes of each bacterial strain was evaluated using polymerase chain reaction. Batch experiment results showed that Pseudomonas putida strains OS-3 and -18 completely oxidized 1 mM of arsenite(III) to arsenate(V) within 35Ã¢â‚¬â€œ40 h. In contrast, two arsenate-reducing bacteria isolated from mines, P. putida RS-4 and RS-5, were capable of growing aerobically in growth medium supplemented with up to 66.7 mM arsenate(V), which are significantly higher concentration than those tolerated by other arsenic-resistant bacteria. These results suggest that newly isolated indigenous arsenic-resistant bacteria may provide a better understanding of the molecular geomicrobiology and may be applied to the bioremediation of arsenic-contaminated mines in Korea. Ecologically, the redox potential plays an important role in arsenic toxicity and mobility in As-contaminated mine areas, as it facilitates the biogeochemical cycling activity of Pseudomonas sp. groups. [ABSTRACT FROM AUTHOR] Copyright of Applied Microbiology & Biotechnology is the property of Springer Science & Business Media B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","The ars genotype characterization of arsenic-resistant bacteria from arsenic-contaminated gold-silver mines in the Republic of KoreaAbs: The isolates were identified on the basis of ars genotype characteristics as well as arsenic oxidation/reduction analysis based on the molecular detection characterization. Diversity, pH range (4.0 to 7.0), location, and ars features were assessed for four arsenic-contaminated pond sites and six arsenic tailings located in the Duck-um mine and Myoung-bong mine areas. The presence of ars genes in the genomes of each bacterial strain was evaluated using polymerase chain reaction. Batch experiment results showed that Pseudomonas putida strains OS-3 and -18 completely oxidized 1 mM of arsenite(III) to arsenate(V) within 35Ã¢â‚¬â€œ40 h. In contrast, two arsenate-reducing bacteria isolated from mines, P. putida RS-4 and RS-5, were capable of growing aerobically in growth medium supplemented with up to 66.7 mM arsenate(V), which are significantly higher concentration than those tolerated by other arsenic-resistant bacteria. These results suggest that newly isolated indigenous arsenic-resistant bacteria may provide a better understanding of the molecular geomicrobiology and may be applied to the bioremediation of arsenic-contaminated mines in Korea. Ecologically, the redox potential plays an important role in arsenic toxicity and mobility in As-contaminated mine areas, as it facilitates the biogeochemical cycling activity of Pseudomonas sp. groups. [ABSTRACT FROM AUTHOR] Copyright of Applied Microbiology & Biotechnology is the property of Springer Science & Business Media B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
290,Hays et al. 2006,Arsenic and Cigarette Smoke Synergistically Increase DNA Oxidation in the Lung," Epidemiological evidence has indicated that arsenic and cigarette smoking exposure act synergistically to increase the incidence oflung cancer. Since oxidative damage of DNA has been linked to cancer, our hypothesis is that aerosolized arsenic and cigarette smoke work synergistically to increase oxidative stress and increase DNA oxidation in the lung. To test this hypothesis male Syrian golden hamsters were exposed to room air (control), aerosolized arsenic compounds (3.2 mg/m3 for 30 minutes), cigarette smoke (5 mg/m3 for 30 minutes), or both smoke and arsenic. Exposures were for 5 days/week for 5 or 28-days. Animals were sacrificed one day after the last exposure. In the 28-day group, glutathione levels and DNA oxidation (8-oxo-2'-deoxyguanosine (8-oxo-dG)) were detel1nined. Our results show that in the 28-day arsenic/smoke group there was a significant decrease in both the reduced and total glutathione levels compared with arsenic or smoke alone. This correlated with a 5-fold increase in DNA oxidation as shown by HPLC. Immunohistochemical localization of 8-oxo-dG showed increase staining in nuclei of airway epithelium and subadjacent interstitial cells. These results show that dual exposure of arsenic and cigarette smoke at environmentally relevant levels can act synergistically to cause DNA damage.","Arsenic and Cigarette Smoke Synergistically Increase DNA Oxidation in the LungAbs: Epidemiological evidence has indicated that arsenic and cigarette smoking exposure act synergistically to increase the incidence oflung cancer. Since oxidative damage of DNA has been linked to cancer, our hypothesis is that aerosolized arsenic and cigarette smoke work synergistically to increase oxidative stress and increase DNA oxidation in the lung. To test this hypothesis male Syrian golden hamsters were exposed to room air (control), aerosolized arsenic compounds (3.2 mg/m3 for 30 minutes), cigarette smoke (5 mg/m3 for 30 minutes), or both smoke and arsenic. Exposures were for 5 days/week for 5 or 28-days. Animals were sacrificed one day after the last exposure. In the 28-day group, glutathione levels and DNA oxidation (8-oxo-2'-deoxyguanosine (8-oxo-dG)) were detel1nined. Our results show that in the 28-day arsenic/smoke group there was a significant decrease in both the reduced and total glutathione levels compared with arsenic or smoke alone. This correlated with a 5-fold increase in DNA oxidation as shown by HPLC. Immunohistochemical localization of 8-oxo-dG showed increase staining in nuclei of airway epithelium and subadjacent interstitial cells. These results show that dual exposure of arsenic and cigarette smoke at environmentally relevant levels can act synergistically to cause DNA damage."
291,Li et al. 2009,The molecular resonance fluorescence method for determination of arsenic in hair samples," Abstract: A molecular resonance fluorescence quenching method for the determination of arsenic was proposed. The method is based on the quenching effect of As (V) on the molecular resonance fluorescence of Rhodamine B (RhB) in sulfuric acid medium and in the presence of molybdate and PVA. The influences of acidity, chemical and manifold variables on the sensitivity were studied. At the optimized conditions, the linear range for the determination of arsenic was 2.0Ãƒâ€”10<sup>Ã¢Ë†â€™3</sup>Ã¢â‚¬â€œ0.12ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> with the detection limit of 1.20Ãƒâ€”10<sup>Ã¢Ë†â€™9</sup> gml<sup>Ã¢Ë†â€™1</sup>. The relative standard deviations for the eleven replicate determinations of 0.006ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> and 0.060ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> of arsenic were 1.12% and 1.61%, respectively. The proposed method was applied successfully for the determination of trace arsenic in hair samples with the recoveries of 94.8Ã¢â‚¬â€œ104.6%. [Copyright 2009 Elsevier] Copyright of Spectrochimica Acta Part A: Molecular & Biomolecular Spectroscopy is the property of Elsevier Science Publishing Company, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","The molecular resonance fluorescence method for determination of arsenic in hair samplesAbs: Abstract: A molecular resonance fluorescence quenching method for the determination of arsenic was proposed. The method is based on the quenching effect of As (V) on the molecular resonance fluorescence of Rhodamine B (RhB) in sulfuric acid medium and in the presence of molybdate and PVA. The influences of acidity, chemical and manifold variables on the sensitivity were studied. At the optimized conditions, the linear range for the determination of arsenic was 2.0Ãƒâ€”10<sup>Ã¢Ë†â€™3</sup>Ã¢â‚¬â€œ0.12ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> with the detection limit of 1.20Ãƒâ€”10<sup>Ã¢Ë†â€™9</sup> gml<sup>Ã¢Ë†â€™1</sup>. The relative standard deviations for the eleven replicate determinations of 0.006ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> and 0.060ÃŽÂ¼gml<sup>Ã¢Ë†â€™1</sup> of arsenic were 1.12% and 1.61%, respectively. The proposed method was applied successfully for the determination of trace arsenic in hair samples with the recoveries of 94.8Ã¢â‚¬â€œ104.6%. [Copyright 2009 Elsevier] Copyright of Spectrochimica Acta Part A: Molecular & Biomolecular Spectroscopy is the property of Elsevier Science Publishing Company, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
292,Mahata et al. 2008,Effect of Selenium and Vitamin E Supplementation on Plasma Protein Carbonyl Levels in Patients With Arsenic-Related Skin Lesions," An estimated 35 million people in Bangladesh have been chronically exposed to arsenic in drinking water and are at risk of an array of adverse health conditions. The mechanisms of arsenic toxicity have not been well established; however, oxidative stress has been one commonly proposed pathway. In this study, we evaluated the effect of antioxidant supplementation on plasma protein oxidation among patients with arsenical skin lesions participating in a randomized double-blinded placebo-controlled trial of vitamin E and selenium. Subjects were randomized to 1 of 4 treatments arms (vitamin E, selenium, combination, or placebo) and were treated for a 6-mo period. We observed a dose-dependent increase in adjusted protein carbonyl levels by arsenic exposure status in the pretreatment samples, although trends were not statistically significant. Following the 6-mo intervention, there was a decrease in protein carbonyl levels in each treatment group, although no resultant decrease was significantly different from that seen in the placebo group. Although we did not see a notable effect of selenium or vitamin E supplementation on changes in protein carbonyl levels, these preliminary data demonstrate a feasible methodological approach for the assessment of plasma protein carbonyls in relation to environmental toxicants in a human population and their potential use as endpoints in intervention trials. [ABSTRACT FROM AUTHOR] Copyright of Nutrition & Cancer is the property of Lawrence Erlbaum Associates and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","Effect of Selenium and Vitamin E Supplementation on Plasma Protein Carbonyl Levels in Patients With Arsenic-Related Skin LesionsAbs: An estimated 35 million people in Bangladesh have been chronically exposed to arsenic in drinking water and are at risk of an array of adverse health conditions. The mechanisms of arsenic toxicity have not been well established; however, oxidative stress has been one commonly proposed pathway. In this study, we evaluated the effect of antioxidant supplementation on plasma protein oxidation among patients with arsenical skin lesions participating in a randomized double-blinded placebo-controlled trial of vitamin E and selenium. Subjects were randomized to 1 of 4 treatments arms (vitamin E, selenium, combination, or placebo) and were treated for a 6-mo period. We observed a dose-dependent increase in adjusted protein carbonyl levels by arsenic exposure status in the pretreatment samples, although trends were not statistically significant. Following the 6-mo intervention, there was a decrease in protein carbonyl levels in each treatment group, although no resultant decrease was significantly different from that seen in the placebo group. Although we did not see a notable effect of selenium or vitamin E supplementation on changes in protein carbonyl levels, these preliminary data demonstrate a feasible methodological approach for the assessment of plasma protein carbonyls in relation to environmental toxicants in a human population and their potential use as endpoints in intervention trials. [ABSTRACT FROM AUTHOR] Copyright of Nutrition & Cancer is the property of Lawrence Erlbaum Associates and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
293,Mishra and Flora 2008,Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure," Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain -- parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes. [ABSTRACT FROM AUTHOR] Copyright of Toxicology & Industrial Health is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposureAbs: Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain -- parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes. [ABSTRACT FROM AUTHOR] Copyright of Toxicology & Industrial Health is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
294,Saito et al. 2008,"Interactions of arsenic with zinc, copper and iron in human hepatic cells"," The purpose of this study is to examine interactions of arsenic (As) with copper (Cu), zinc (Zn) and iron (Fe) in human hepatic cells. The 100 ÃŽÂ¼M As and Cu alone reduced viability of the cells by 25 and 90%, respectively. For the other metals (Zn and Fe), no significant difference was found as compared to the control. The concentrations of 100 ÃŽÂ¼M Cu alone decreased in cell viability significantly as compared with control. For the 10 ÃŽÂ¼M As + 5 ÃŽÂ¼M to 100 ÃŽÂ¼M Zn, no significant changes were observed as compared to As alone. Although 5 - 100 ÃŽÂ¼M Fe alone had no effect on the proliferation of human hepatic cells, there were significant increases in cell viability after exposure to 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Fe as compared to As alone. Significant increases in cell viability were not observed below the concentrations of 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Fe. For the concentrations of 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Cu, a significant decrease was found as compared to As alone. These results indicated that the high concentration of Fe protected against As toxicity in human hepatic cells and that the high concentration of Cu accelerated As toxicity against human hepatic cells. [ABSTRACT FROM AUTHOR] Copyright of Trace Elements & Electrolytes is the property of Dustri-Verlag Dr. Karl Feistle GmbH & Co., KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","Interactions of arsenic with zinc, copper and iron in human hepatic cellsAbs: The purpose of this study is to examine interactions of arsenic (As) with copper (Cu), zinc (Zn) and iron (Fe) in human hepatic cells. The 100 ÃŽÂ¼M As and Cu alone reduced viability of the cells by 25 and 90%, respectively. For the other metals (Zn and Fe), no significant difference was found as compared to the control. The concentrations of 100 ÃŽÂ¼M Cu alone decreased in cell viability significantly as compared with control. For the 10 ÃŽÂ¼M As + 5 ÃŽÂ¼M to 100 ÃŽÂ¼M Zn, no significant changes were observed as compared to As alone. Although 5 - 100 ÃŽÂ¼M Fe alone had no effect on the proliferation of human hepatic cells, there were significant increases in cell viability after exposure to 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Fe as compared to As alone. Significant increases in cell viability were not observed below the concentrations of 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Fe. For the concentrations of 10 ÃŽÂ¼M As + 100 ÃŽÂ¼M Cu, a significant decrease was found as compared to As alone. These results indicated that the high concentration of Fe protected against As toxicity in human hepatic cells and that the high concentration of Cu accelerated As toxicity against human hepatic cells. [ABSTRACT FROM AUTHOR] Copyright of Trace Elements & Electrolytes is the property of Dustri-Verlag Dr. Karl Feistle GmbH & Co., KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
295,Slotnick et al. 2008,"Intra-individual variability in toenail arsenic concentrations in a Michigan population, USA"," Arsenic concentration in toenail clippings is used as a biomarker of exposure in epidemiological studies, often under the assumption that a single measurement represents long-term exposure. For this assumption to hold, the measured arsenic concentrations must be stable over time, yet temporal variability has not been adequately assessed. This study aims to evaluate temporal variability in multiple toenail samples collected from a population exposed to drinking water arsenic levels <100 ÃŽÂ¼g/l. Our objectives are to investigate factors responsible for biomarker variability and to assess the suitability of single versus multiple measurements for determining exposure in epidemiological studies. Multiple toenail and drinking water samples were collected from 254 participants enrolled in a caseÃ¢â‚¬â€œcontrol study of arsenic exposure and bladder cancer in Michigan, USA; participants also answered questions on water consumption. Toenail samples collected an average of 14 months apart were positively correlated, although a substantial amount of variability was detected (r=0.43, P<0.0001, n=236). Arsenic concentration in drinking water was stable and small changes in drinking water arsenic concentration did not explain variability in toenail arsenic concentration. Change in drinking water consumption, however, was significant in predicting differences in toenail arsenic concentration. Stronger correlations between drinking water arsenic concentration and intake and toenail arsenic concentration were observed when two toenail samples were averaged, suggesting that multiple measurements may more accurately reflect exposure. When exposure was categorized into tertiles and other pre-determined categories, 25Ã¢â‚¬â€œ40% of exposures were differentially classified. Only a small percentage (<4%), however, were classified as having low exposure using a single measurement and high exposure when an average of two measurements was used. These results suggest that the use of... [ABSTRACT FROM AUTHOR] Copyright of Journal of Exposure Science & Environmental Epidemiology is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","Intra-individual variability in toenail arsenic concentrations in a Michigan population, USAAbs: Arsenic concentration in toenail clippings is used as a biomarker of exposure in epidemiological studies, often under the assumption that a single measurement represents long-term exposure. For this assumption to hold, the measured arsenic concentrations must be stable over time, yet temporal variability has not been adequately assessed. This study aims to evaluate temporal variability in multiple toenail samples collected from a population exposed to drinking water arsenic levels <100 ÃŽÂ¼g/l. Our objectives are to investigate factors responsible for biomarker variability and to assess the suitability of single versus multiple measurements for determining exposure in epidemiological studies. Multiple toenail and drinking water samples were collected from 254 participants enrolled in a caseÃ¢â‚¬â€œcontrol study of arsenic exposure and bladder cancer in Michigan, USA; participants also answered questions on water consumption. Toenail samples collected an average of 14 months apart were positively correlated, although a substantial amount of variability was detected (r=0.43, P<0.0001, n=236). Arsenic concentration in drinking water was stable and small changes in drinking water arsenic concentration did not explain variability in toenail arsenic concentration. Change in drinking water consumption, however, was significant in predicting differences in toenail arsenic concentration. Stronger correlations between drinking water arsenic concentration and intake and toenail arsenic concentration were observed when two toenail samples were averaged, suggesting that multiple measurements may more accurately reflect exposure. When exposure was categorized into tertiles and other pre-determined categories, 25Ã¢â‚¬â€œ40% of exposures were differentially classified. Only a small percentage (<4%), however, were classified as having low exposure using a single measurement and high exposure when an average of two measurements was used. These results suggest that the use of... [ABSTRACT FROM AUTHOR] Copyright of Journal of Exposure Science & Environmental Epidemiology is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
296,Straub et al. 2008,Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase-generated superoxide," Environmental arsenic exposure, through drinking contaminated water, is a significant risk factor for developing vascular diseases and is associated with liver portal hypertension, vascular shunting, and portal fibrosis through unknown mechanisms. We found that the addition of low doses of arsenite to the drinking water of mice resulted in marked pathologic remodeling in liver sinusoidal endothelial cells (SECs), including SEC defenestration, capillarization, increased junctional PECAM-1 expression, protein nitration, and decreased liver clearance of modified albumin. Furthermore, the pathologic changes observed after in vivo exposure were recapitulated in isolated mouse SECs exposed to arsenic in culture. To investigate the role of NADPH oxidase-generated ROS in this remodeling, we examined the effect of arsenite in the drinking water of mice deficient for the p47 subunit of the NADPH oxidase and found that knockout mice were protected from arsenite-induced capillarization and protein nitration. Furthermore, ex vivo arsenic exposure increased SEC superoxide generation, and this effect was inhibited by addition of a Nox2 inhibitor and quenched by the cellpermeant superoxide scavenger. In addition, inhibiting either oxidant generation or Rac1-GTPase blocked ex vivo arsenic-stimulated SEC differentiation and dysfunction. Our data indicate that a Nox2-based oxidase is required for SEC capillarization and that it may play a central role in vessel remodeling following environmentally relevant arsenic exposures. [ABSTRACT FROM AUTHOR] Copyright of Journal of Clinical Investigation is the property of American Society for Clinical Investigation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)","Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase-generated superoxideAbs: Environmental arsenic exposure, through drinking contaminated water, is a significant risk factor for developing vascular diseases and is associated with liver portal hypertension, vascular shunting, and portal fibrosis through unknown mechanisms. We found that the addition of low doses of arsenite to the drinking water of mice resulted in marked pathologic remodeling in liver sinusoidal endothelial cells (SECs), including SEC defenestration, capillarization, increased junctional PECAM-1 expression, protein nitration, and decreased liver clearance of modified albumin. Furthermore, the pathologic changes observed after in vivo exposure were recapitulated in isolated mouse SECs exposed to arsenic in culture. To investigate the role of NADPH oxidase-generated ROS in this remodeling, we examined the effect of arsenite in the drinking water of mice deficient for the p47 subunit of the NADPH oxidase and found that knockout mice were protected from arsenite-induced capillarization and protein nitration. Furthermore, ex vivo arsenic exposure increased SEC superoxide generation, and this effect was inhibited by addition of a Nox2 inhibitor and quenched by the cellpermeant superoxide scavenger. In addition, inhibiting either oxidant generation or Rac1-GTPase blocked ex vivo arsenic-stimulated SEC differentiation and dysfunction. Our data indicate that a Nox2-based oxidase is required for SEC capillarization and that it may play a central role in vessel remodeling following environmentally relevant arsenic exposures. [ABSTRACT FROM AUTHOR] Copyright of Journal of Clinical Investigation is the property of American Society for Clinical Investigation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)"
297,Chung et al. 1997,Risk assessment and management of drinking water pollutants in Korea," The contamination of drinking water supply is becoming an increasingly serious problem in Korea. In order to protect public health, there is a need to regulate drinking water pollutants. The purpose of this project, a national project for three years starting from 1992 to 1995, is to assess the health risk of pollutants in drinking water and recommend guidelines and management plans for maintaining good quality of drinking water. This study was conducted to monitor 80 species of chemicals including volatile organic compounds(VOCs), polycyclic aromatic hydrocarbons(PAHs), pesticides and metals in six major rivers and their distribution system for drinking water in Korea, and evaluate health risk due to exposure to these chemicals through four main steps of risk assessment in drinking water. In hazard identification, 80 species of chemicals were identified by the US EPA classification system. In their steps of exposure assessment, sampling of raw, treated and drinking water from the public water supply system have been conducted from 1993 to 1995, and 80 chemicals were analyzed. In dose-response assessment, cancer potencies, unit risk estimates and virtual safety doses of carcinogens were obtained by TOX-RISK, and reference doses and lifetime health advisories of noncarcinogens were calculated. Finally, in the risk characterization of detected chemicals, health risk due to exposure to carcinogens(weight of evidence, A or B) such as vinyl chloride, carbon tetrachloride, 1,2-dichloroethane, benzen, 1,1,1,2-tetrachloroethane, trihalomethanes(THMs), lead and arsenic of tap water in several cities exceeded 10?5 level. We suggest that non-regulated chemicals such as vinyl chloride, carbon tetrachloride and 1,2-dichloroethane should be monitored periodically and be regulated by the Drinking Water Management Act.","Risk assessment and management of drinking water pollutants in KoreaAbs: The contamination of drinking water supply is becoming an increasingly serious problem in Korea. In order to protect public health, there is a need to regulate drinking water pollutants. The purpose of this project, a national project for three years starting from 1992 to 1995, is to assess the health risk of pollutants in drinking water and recommend guidelines and management plans for maintaining good quality of drinking water. This study was conducted to monitor 80 species of chemicals including volatile organic compounds(VOCs), polycyclic aromatic hydrocarbons(PAHs), pesticides and metals in six major rivers and their distribution system for drinking water in Korea, and evaluate health risk due to exposure to these chemicals through four main steps of risk assessment in drinking water. In hazard identification, 80 species of chemicals were identified by the US EPA classification system. In their steps of exposure assessment, sampling of raw, treated and drinking water from the public water supply system have been conducted from 1993 to 1995, and 80 chemicals were analyzed. In dose-response assessment, cancer potencies, unit risk estimates and virtual safety doses of carcinogens were obtained by TOX-RISK, and reference doses and lifetime health advisories of noncarcinogens were calculated. Finally, in the risk characterization of detected chemicals, health risk due to exposure to carcinogens(weight of evidence, A or B) such as vinyl chloride, carbon tetrachloride, 1,2-dichloroethane, benzen, 1,1,1,2-tetrachloroethane, trihalomethanes(THMs), lead and arsenic of tap water in several cities exceeded 10?5 level. We suggest that non-regulated chemicals such as vinyl chloride, carbon tetrachloride and 1,2-dichloroethane should be monitored periodically and be regulated by the Drinking Water Management Act."
298,Maharjan et al. 2005,Arsenic contamination in drinking water and skin manifestations in lowland Nepal: The first community-based survey," A community-based, dose-response study on arsenic contamination was conducted in three communities in Terai in lowland Nepal. The arsenic concentration of all the tube wells in use (n = 146) and the prevalence of arsenic-induced skin manifestation among 1,343 (approximately 80% of the inhabitants) subjects indicated the existence of a highly contaminated area in Terai. It was found that overall prevalence of arsenicosis among the subjects > or = 15 years old was 6.9%, which was comparable to those found by the same examiner in arsenic-contaminated areas in Bangladesh, and that males had prevalence a twice as high as females, which could not be explained by the difference in the exposure level.","Arsenic contamination in drinking water and skin manifestations in lowland Nepal: The first community-based surveyAbs: A community-based, dose-response study on arsenic contamination was conducted in three communities in Terai in lowland Nepal. The arsenic concentration of all the tube wells in use (n = 146) and the prevalence of arsenic-induced skin manifestation among 1,343 (approximately 80% of the inhabitants) subjects indicated the existence of a highly contaminated area in Terai. It was found that overall prevalence of arsenicosis among the subjects > or = 15 years old was 6.9%, which was comparable to those found by the same examiner in arsenic-contaminated areas in Bangladesh, and that males had prevalence a twice as high as females, which could not be explained by the difference in the exposure level."
299,Mahata et al. 2004,Effect of sodium arsenite on peripheral lymphocytes in vitro: Individual susceptibility among a population exposed to arsenic through the drinking water," Arsenic (As) contamination in ground water has affected more than 19 countries. Approximately 36 million people in the Bengal delta alone are exposed to this toxicant via drinking water (>50 µg/l) and are at potential health risk. Chronic ingestion of As via drinking water is associated with occurrence of skin lesions, cancer and other arsenic-induced diseases in West Bengal, India. An in vitro cytogenetic study was performed utilizing chromosomal aberrations (CA) in lymphocytes treated with sodium arsenite (0–5 µM) in six symptomatic (having arsenic-related skin lesions) individuals, six age- and sex-matched As-exposed asymptomatic (no arsenic-related skin lesions) individuals and six control individuals with similar socio-economic status residing in non-affected districts of West Bengal with no evidence of As exposure. The mean As content in nails and hair was 9.61 and 5.23 µg/g in symptomatic, 3.48 and 2.17 µg/g in asymptomatic and 0.42 and 0.33 µg/g in the control individuals, respectively. The main aim of our study was to determine whether genotoxic effects differed in the lymphocytes of the control (no exposure to arsenic), asymptomatic and symptomatic individuals after in vitro treatment with sodium arsenite. Although both the exposed groups had chronic exposure to As through the drinking water, individuals with skin lesions accumulated more As in their nails and hair and excreted less in urine (127.80 versus 164.15 µg/l). The results show that sodium arsenite induced a significantly higher percentage of aberrant cells in the lymphocytes of control individuals than in the lymphocytes of both the exposed groups. Within the two exposed groups As induced higher incidences of CA in the symptomatic than the asymptomatic individuals. These results suggest that asymptomatic individuals have relatively lower sensitivity and susceptibility to induction of genetic damage by As compared with the symptomatic individuals.","Effect of sodium arsenite on peripheral lymphocytes in vitro: Individual susceptibility among a population exposed to arsenic through the drinking waterAbs: Arsenic (As) contamination in ground water has affected more than 19 countries. Approximately 36 million people in the Bengal delta alone are exposed to this toxicant via drinking water (>50 µg/l) and are at potential health risk. Chronic ingestion of As via drinking water is associated with occurrence of skin lesions, cancer and other arsenic-induced diseases in West Bengal, India. An in vitro cytogenetic study was performed utilizing chromosomal aberrations (CA) in lymphocytes treated with sodium arsenite (0–5 µM) in six symptomatic (having arsenic-related skin lesions) individuals, six age- and sex-matched As-exposed asymptomatic (no arsenic-related skin lesions) individuals and six control individuals with similar socio-economic status residing in non-affected districts of West Bengal with no evidence of As exposure. The mean As content in nails and hair was 9.61 and 5.23 µg/g in symptomatic, 3.48 and 2.17 µg/g in asymptomatic and 0.42 and 0.33 µg/g in the control individuals, respectively. The main aim of our study was to determine whether genotoxic effects differed in the lymphocytes of the control (no exposure to arsenic), asymptomatic and symptomatic individuals after in vitro treatment with sodium arsenite. Although both the exposed groups had chronic exposure to As through the drinking water, individuals with skin lesions accumulated more As in their nails and hair and excreted less in urine (127.80 versus 164.15 µg/l). The results show that sodium arsenite induced a significantly higher percentage of aberrant cells in the lymphocytes of control individuals than in the lymphocytes of both the exposed groups. Within the two exposed groups As induced higher incidences of CA in the symptomatic than the asymptomatic individuals. These results suggest that asymptomatic individuals have relatively lower sensitivity and susceptibility to induction of genetic damage by As compared with the symptomatic individuals."
300,Cheraghali et al. 2007,Fatalities following skin exposure to arsenic," Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients.","Fatalities following skin exposure to arsenicAbs: Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients."
301,Marcos et al. 2006,Metabolic profile in workers occupationally exposed to arsenic: Role of GST polymorphisms," Arsenic is a well-known human carcinogen with a ubiquitous distribution in the natural environment. Chronic exposure to inorganic arsenic involves a biotransformation process that leds to the main excretion of organic methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species. Interindividual variation in arsenic metabolism has been extensively reported, and polymorphisms in genes involved in such process could be related to changes in the arsenic excretion profile and the response to chronic exposures. Our analysis of the metabolic profiles in three groups of workers exposed to different arsenic exposure levels showed high amounts of inorganic arsenic and MMA in the most-exposed workers versus the least-exposed workers, in whom high amounts of DMA were observed. With respect to the role of different genetic polymorphisms in the glutathione S-transferase (GST) genes in the modulation of the urinary profiles, for the overall population only a tendency was just observed between GSTM1 null and MMA excretion as well as between GSTP1 val/val and DMA excretion.","Metabolic profile in workers occupationally exposed to arsenic: Role of GST polymorphismsAbs: Arsenic is a well-known human carcinogen with a ubiquitous distribution in the natural environment. Chronic exposure to inorganic arsenic involves a biotransformation process that leds to the main excretion of organic methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species. Interindividual variation in arsenic metabolism has been extensively reported, and polymorphisms in genes involved in such process could be related to changes in the arsenic excretion profile and the response to chronic exposures. Our analysis of the metabolic profiles in three groups of workers exposed to different arsenic exposure levels showed high amounts of inorganic arsenic and MMA in the most-exposed workers versus the least-exposed workers, in whom high amounts of DMA were observed. With respect to the role of different genetic polymorphisms in the glutathione S-transferase (GST) genes in the modulation of the urinary profiles, for the overall population only a tendency was just observed between GSTM1 null and MMA excretion as well as between GSTP1 val/val and DMA excretion."
302,Marnell et al. 2003,Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene and changes in urinary arsenic profiles," Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.","Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene and changes in urinary arsenic profilesAbs: Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure."
303,Marshall et al. 2007,Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water," BACKGROUND: Region II of Chile (the second most northerly administrative region) experienced dramatic increases in average arsenic water concentrations beginning in 1958, followed by marked declines in the 1970s when water treatment plants were installed. This history provides a unique opportunity to study time trends in the development of arsenic-related cancers, including lung and bladder cancers. METHODS: We investigated lung and bladder cancer mortality from 1950 to 2000 for region II compared with region V, where drinking water was not contaminated with arsenic. Mortality data were obtained from 218,174 death certificates for the two regions for 1950-1970 and from mortality data tapes that identified 307,541 deaths in the two regions for 1971-2000. Poisson regression models were used to identify time trends in rate ratios (RRs) of mortality from lung and bladder cancers comparing region II with region V. RESULTS: Lung and bladder cancer mortality rate ratios for region II compared with region V started to increase about 10 years after high arsenic exposures commenced and continued to rise until peaking in 1986-1997. The peak lung cancer mortality RRs were 3.61 (95% confidence interval [CI] = 3.13 to 4.16) for men and 3.26 (95% CI = 2.50 to 4.23) for women. The peak bladder cancer RRs were 6.10 (95% CI = 3.97 to 9.39) for men and 13.8 (95% CI = 7.74 to 24.5) for women. Combined lung and bladder cancer mortality rates in region II were highest in the period 1992-1994, with mortality rates of 153 and 50 per 100,000 men and women, respectively, in region II compared with 54 and 19 per 100,000 in region V. CONCLUSIONS: Such large increases in total population cancer mortality rates have, to our knowledge, not been documented for any other environmental exposure. The long latency pattern is noteworthy, with mortality from lung and bladder cancers continuing to be high until the late 1990s, even though major decreases in arsenic exposure occurred more than 25 years earlier.","Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking waterAbs: BACKGROUND: Region II of Chile (the second most northerly administrative region) experienced dramatic increases in average arsenic water concentrations beginning in 1958, followed by marked declines in the 1970s when water treatment plants were installed. This history provides a unique opportunity to study time trends in the development of arsenic-related cancers, including lung and bladder cancers. METHODS: We investigated lung and bladder cancer mortality from 1950 to 2000 for region II compared with region V, where drinking water was not contaminated with arsenic. Mortality data were obtained from 218,174 death certificates for the two regions for 1950-1970 and from mortality data tapes that identified 307,541 deaths in the two regions for 1971-2000. Poisson regression models were used to identify time trends in rate ratios (RRs) of mortality from lung and bladder cancers comparing region II with region V. RESULTS: Lung and bladder cancer mortality rate ratios for region II compared with region V started to increase about 10 years after high arsenic exposures commenced and continued to rise until peaking in 1986-1997. The peak lung cancer mortality RRs were 3.61 (95% confidence interval [CI] = 3.13 to 4.16) for men and 3.26 (95% CI = 2.50 to 4.23) for women. The peak bladder cancer RRs were 6.10 (95% CI = 3.97 to 9.39) for men and 13.8 (95% CI = 7.74 to 24.5) for women. Combined lung and bladder cancer mortality rates in region II were highest in the period 1992-1994, with mortality rates of 153 and 50 per 100,000 men and women, respectively, in region II compared with 54 and 19 per 100,000 in region V. CONCLUSIONS: Such large increases in total population cancer mortality rates have, to our knowledge, not been documented for any other environmental exposure. The long latency pattern is noteworthy, with mortality from lung and bladder cancers continuing to be high until the late 1990s, even though major decreases in arsenic exposure occurred more than 25 years earlier."
304,Marsit et al. 2006,Carcinogen exposure and epigenetic silencing in bladder cancer," Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. Animal and in vitro studies have suggested that arsenic, tobacco carcinogens, and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer (n = 351), the relationship between epigenetic silencing of the tumor-suppressor genes, p16(INK4A), RASSF1A, PRSS3, and the four SFRP genes and exposure to both tobacco and arsenic in bladder cancer. Promotor methylation silencing of each of these genes occurred in approximately 30-50% of bladder cancers. Epigenetic silencing of RASSF1A and PRSS3 and any of the SFRP genes were each significantly associated with advanced tumor stage (P < 0.001, P < 0.04, and P < 0.005, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P < 0.02) and PRSS3 (P < 0.1) but not p16(INK4A) or SFRP promotor methylation, in models adjusted for stage and other risk factors. Cigarette smoking was associated with a greater than twofold increased risk of promotor methylation of the p16(INK4A) gene, with greater risk seen in patients with exposures more recent to disease diagnosis, and smoking was also significantly associated with any SFRP gene methylation (P < 0.01). These results from human bladder tumors, add to the body of animal and in vitro evidence that suggests bladder carcinogens play a crucial role in the induction of important epigenetic alterations.","Carcinogen exposure and epigenetic silencing in bladder cancerAbs: Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. Animal and in vitro studies have suggested that arsenic, tobacco carcinogens, and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer (n = 351), the relationship between epigenetic silencing of the tumor-suppressor genes, p16(INK4A), RASSF1A, PRSS3, and the four SFRP genes and exposure to both tobacco and arsenic in bladder cancer. Promotor methylation silencing of each of these genes occurred in approximately 30-50% of bladder cancers. Epigenetic silencing of RASSF1A and PRSS3 and any of the SFRP genes were each significantly associated with advanced tumor stage (P < 0.001, P < 0.04, and P < 0.005, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P < 0.02) and PRSS3 (P < 0.1) but not p16(INK4A) or SFRP promotor methylation, in models adjusted for stage and other risk factors. Cigarette smoking was associated with a greater than twofold increased risk of promotor methylation of the p16(INK4A) gene, with greater risk seen in patients with exposures more recent to disease diagnosis, and smoking was also significantly associated with any SFRP gene methylation (P < 0.01). These results from human bladder tumors, add to the body of animal and in vitro evidence that suggests bladder carcinogens play a crucial role in the induction of important epigenetic alterations."
305,Marsit et al. 2006,Carcinogen exposure and gene promoter hypermethylation in bladder cancer," Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. In particular, the mechanism by which arsenic induces bladder cancer and the effects of lower environmental levels of exposure remain uncertain. Animal and in-vitro studies have suggested that arsenic and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer, the relationship between epigenetic silencing of three tumor suppressor genes, p16INK4A, RASSF1A and PRSS3, and exposure to both tobacco and arsenic in bladder cancer. Promoter methylation of each of these genes occurred in ~30% of bladder cancers, and both RASSF1A and PRSS3 promoter methylation were associated with advanced tumor stage (P < 0.001 and P < 0.04, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P < 0.02) and PRSS3 (P < 0.1) but not p16INK4A promoter methylation, in models adjusted for stage and other factors. Cigarette smoking was associated with a >2-fold increased risk of promoter methylation of the p16INK4A gene only, with greater risk seen in patients with exposures more recent to disease diagnosis. These results, from human bladder tumors, add to the body of animal and in vitro evidence that suggests a role in epigenetic alterations for bladder carcinogens.","Carcinogen exposure and gene promoter hypermethylation in bladder cancerAbs: Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. In particular, the mechanism by which arsenic induces bladder cancer and the effects of lower environmental levels of exposure remain uncertain. Animal and in-vitro studies have suggested that arsenic and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer, the relationship between epigenetic silencing of three tumor suppressor genes, p16INK4A, RASSF1A and PRSS3, and exposure to both tobacco and arsenic in bladder cancer. Promoter methylation of each of these genes occurred in ~30% of bladder cancers, and both RASSF1A and PRSS3 promoter methylation were associated with advanced tumor stage (P < 0.001 and P < 0.04, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P < 0.02) and PRSS3 (P < 0.1) but not p16INK4A promoter methylation, in models adjusted for stage and other factors. Cigarette smoking was associated with a >2-fold increased risk of promoter methylation of the p16INK4A gene only, with greater risk seen in patients with exposures more recent to disease diagnosis. These results, from human bladder tumors, add to the body of animal and in vitro evidence that suggests a role in epigenetic alterations for bladder carcinogens."
306,Dakeishi et al. 2006,Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder," Arsenic toxicity is a global health problem affecting many millions of people. The main source of exposure is drinking water contaminated by natural geological sources. Current risk assessment is based on the recognized carcinogenicity of arsenic, but neurotoxic risks have been overlooked. In 1955, an outbreak of arsenic poisoning occurred among Japanese infants, with more than 100 deaths. The source was contaminated milk powder produced by the Morinaga company. Detailed accounts of the Morinaga dried milk poisoning were published in Japanese only, and an overview of this poisoning incident and its long-term consequences is therefore presented. From analyses available, the arsenic concentration in milk made from the Morinaga milk powder is calculated to be about 4–7 mg/L, corresponding to daily doses slightly above 500 ?g/kg body weight. Lower exposures would result from using diluted milk. Clinical poisoning cases occurred after a few weeks of exposure, with a total dose of about 60 mg. This experience provides clear-cut evidence for hazard assessment of the developmental neurotoxicity. At the present time, more than 600 surviving victims, now in their 50s, have been reported to suffer from severe sequelae, such as mental retardation, neurological diseases, and other disabilities. Along with more recent epidemiological studies of children with environmental arsenic exposures, the data amply demonstrate the need to consider neurotoxicity as a key concern in risk assessment of inorganic arsenic exposure.","Long-term consequences of arsenic poisoning during infancy due to contaminated milk powderAbs: Arsenic toxicity is a global health problem affecting many millions of people. The main source of exposure is drinking water contaminated by natural geological sources. Current risk assessment is based on the recognized carcinogenicity of arsenic, but neurotoxic risks have been overlooked. In 1955, an outbreak of arsenic poisoning occurred among Japanese infants, with more than 100 deaths. The source was contaminated milk powder produced by the Morinaga company. Detailed accounts of the Morinaga dried milk poisoning were published in Japanese only, and an overview of this poisoning incident and its long-term consequences is therefore presented. From analyses available, the arsenic concentration in milk made from the Morinaga milk powder is calculated to be about 4–7 mg/L, corresponding to daily doses slightly above 500 ?g/kg body weight. Lower exposures would result from using diluted milk. Clinical poisoning cases occurred after a few weeks of exposure, with a total dose of about 60 mg. This experience provides clear-cut evidence for hazard assessment of the developmental neurotoxicity. At the present time, more than 600 surviving victims, now in their 50s, have been reported to suffer from severe sequelae, such as mental retardation, neurological diseases, and other disabilities. Along with more recent epidemiological studies of children with environmental arsenic exposures, the data amply demonstrate the need to consider neurotoxicity as a key concern in risk assessment of inorganic arsenic exposure."
307,Danaee et al. 2004,Low dose exposure to sodium arsenite synergistically interacts with UV radiation to induce mutations and alter DNA repair in human cells," Inorganic arsenic is a known human carcinogen, yet its mechanism of action remains poorly understood. Epidemiological data suggest that arsenic exposure interacts with UV radiation exposure to increase the risk of skin cancer. Studies have suggested that arsenic is able to impair DNA repair enzymes and alter the repair of UV-induced DNA damage. Here we have tested the hypothesis that arsenite [As(III)] and UV interact synergistically to enhance mutagenesis. TK6 human lymphoblastoid cells that are functionally heterozygous at the thymidine kinase (TK) locus were pre-exposed to As(III) alone and in combination with UV. Our data suggest that As(III) is mutagenic only at high doses at the TK locus. As(III) enhanced UV mutagenesis in a more than additive fashion. To investigate the mechanism underlying this synergy we assessed the removal of UV-induced dimers in TK6 cells using the T4 endonuclease-incorporated Comet assay. Pre-treatment with As(III) specifically inhibited the repair of UV-induced pyrimidine dimer-related DNA damage. Taken together, these data suggest that pre-treatment of human cells with arsenic impairs the nucleotide excision repair pathway and leads to enhanced UV mutagenesis.","Low dose exposure to sodium arsenite synergistically interacts with UV radiation to induce mutations and alter DNA repair in human cellsAbs: Inorganic arsenic is a known human carcinogen, yet its mechanism of action remains poorly understood. Epidemiological data suggest that arsenic exposure interacts with UV radiation exposure to increase the risk of skin cancer. Studies have suggested that arsenic is able to impair DNA repair enzymes and alter the repair of UV-induced DNA damage. Here we have tested the hypothesis that arsenite [As(III)] and UV interact synergistically to enhance mutagenesis. TK6 human lymphoblastoid cells that are functionally heterozygous at the thymidine kinase (TK) locus were pre-exposed to As(III) alone and in combination with UV. Our data suggest that As(III) is mutagenic only at high doses at the TK locus. As(III) enhanced UV mutagenesis in a more than additive fashion. To investigate the mechanism underlying this synergy we assessed the removal of UV-induced dimers in TK6 cells using the T4 endonuclease-incorporated Comet assay. Pre-treatment with As(III) specifically inhibited the repair of UV-induced pyrimidine dimer-related DNA damage. Taken together, these data suggest that pre-treatment of human cells with arsenic impairs the nucleotide excision repair pathway and leads to enhanced UV mutagenesis."
308,Das et al. 1996,"Arsenic in groundwater in six districts of West Bengal, India"," Arsenic in groundwater above the WHO maximum permissible limit of 0.05 mg l–1 has been found in six districts of West Bengal covering an area of 34 000 km2 with a population of 30 million. At present, 37 administrative blocks by the side of the River Ganga and adjoining areas are affected. Areas affected by arsenic contamination in groundwater are all located in the upper delta plain, and are mostly in the abandoned meander belt. More than 800 000 people from 312 villages/wards are drinking arsenic contaminated water and amongst them at least 175 000 people show arsenical skin lesions. Thousands of tube-well water in these six districts have been analysed for arsenic species. Hair, nails, scales, urine, liver tissue analyses show elevated concentrations of arsenic in people drinking arsenic-contaminated water for a longer period. The source of the arsenic is geological. Bore-hole sediment analyses show high arsenic concentrations in only few soil layers which is found to be associated with iron-pyrites. Various social problems arise due to arsenical skin lesions in these districts. Malnutrition, poor socio-economic conditions, illiteracy, food habits and intake of arsenic-contaminated water for many years have aggravated the arsenic toxicity. In all these districts, major water demands are met from groundwater and the geochemical reaction, caused by high withdrawal of water may be the cause of arsenic leaching from the source. If alternative water resources are not utilised, a good percentage of the 30 million people of these six districts may suffer from arsenic toxicity in the near future.","Arsenic in groundwater in six districts of West Bengal, IndiaAbs: Arsenic in groundwater above the WHO maximum permissible limit of 0.05 mg l–1 has been found in six districts of West Bengal covering an area of 34 000 km2 with a population of 30 million. At present, 37 administrative blocks by the side of the River Ganga and adjoining areas are affected. Areas affected by arsenic contamination in groundwater are all located in the upper delta plain, and are mostly in the abandoned meander belt. More than 800 000 people from 312 villages/wards are drinking arsenic contaminated water and amongst them at least 175 000 people show arsenical skin lesions. Thousands of tube-well water in these six districts have been analysed for arsenic species. Hair, nails, scales, urine, liver tissue analyses show elevated concentrations of arsenic in people drinking arsenic-contaminated water for a longer period. The source of the arsenic is geological. Bore-hole sediment analyses show high arsenic concentrations in only few soil layers which is found to be associated with iron-pyrites. Various social problems arise due to arsenical skin lesions in these districts. Malnutrition, poor socio-economic conditions, illiteracy, food habits and intake of arsenic-contaminated water for many years have aggravated the arsenic toxicity. In all these districts, major water demands are met from groundwater and the geochemical reaction, caused by high withdrawal of water may be the cause of arsenic leaching from the source. If alternative water resources are not utilised, a good percentage of the 30 million people of these six districts may suffer from arsenic toxicity in the near future."
309,Jackson and Grainge 1975,Arsenic and cancer," Palmar and plantar keratoses developed in seven patients many years after ingeston of trivalent inorganic arsenic. Six had basal cell carcinoma (superficial multicentric type in five), carcinoma &quot;in situ&quot; or squamous cell carcinoma of the skin. Two had systemic carcinoma--one, bilateral breast adenocarcinoma and one, carcinoma of the colon. From these observations and from the findings of a review of the literature, there seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso. It is suspected but not proved to cause other cancers. Although over the last 50 years general exposure to arsenic has greatly decreased, particularly that from insecticides, this element is still found occasionally in drinking water (naturally or as a smelter byproduct), in certain foods and in cigarette smoke.","Arsenic and cancerAbs: Palmar and plantar keratoses developed in seven patients many years after ingeston of trivalent inorganic arsenic. Six had basal cell carcinoma (superficial multicentric type in five), carcinoma &quot;in situ&quot; or squamous cell carcinoma of the skin. Two had systemic carcinoma--one, bilateral breast adenocarcinoma and one, carcinoma of the colon. From these observations and from the findings of a review of the literature, there seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso. It is suspected but not proved to cause other cancers. Although over the last 50 years general exposure to arsenic has greatly decreased, particularly that from insecticides, this element is still found occasionally in drinking water (naturally or as a smelter byproduct), in certain foods and in cigarette smoke."
310,De Chaudhuri et al. 2006,"Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India"," Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and G > A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR = 2.086; 95% CI = 1.318–3.299 and OR = 2.086; 95% CI = 1.257–3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis.","Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, IndiaAbs: Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and G > A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR = 2.086; 95% CI = 1.318–3.299 and OR = 2.086; 95% CI = 1.257–3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis."
311,De et al. 2004,Pulmonary involvement in chronic arsenic poisoning from drinking contaminated ground-water," OBJECTIVES: Chronic arsenic poisoning, due to ingestion of contaminated ground-water, is a major public health problem in West Bengal. It causes multiorgan damage. The present study attempts to objectively investigate the pulmonary involvement by examining the lung function. The nature of lung changes was also evaluated. MATERIAL AND METHODS: One hundred and seven subjects with (cases) and 52 subjects without (controls) chronic arsenic poisoning were examined by spirometry. Forced expiratory volume-I second (FEVI), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were measured. Bronchoalveolar lavage (BAL) was performed in five cases with and five cases without pulmonary involvement. RESULTS: Thirty three (30.8%) cases and four (7.6%) controls (p<0.01) had respiratory involvement. The pattern of involvement in cases was: obstructive- 20(68.9%) (including three (10%) with bronchiectasis), restrictive- 1(3.5%), mixed- 8(27.6%), malignancy- 4(12.1%) (adenocarcinoma-I, squamous cell- 2, undifferentiated- I). FEVI (69.7+/-25.9 [n=105] vs 83.7+/-15.19 [n=51], p=0.0005), FVC (77.4+/-22.7 [n=105] vs 85.6+/-18.23 [n=51], p=0.025), FEVI/FVC (73.6+/-13.38 [n=105] vs 79.1+/-18.65 [n=52], p=0.007) and PEFR (53.9+/-21.52 [n= 103] vs 67.3+/-18.36 [n=51], p=0.0002) (percent of predicted) were all reduced more in cases compared to controls. Worsening of these parameters correlated with increasing degree of arsenic toxicity. Markers of inflammation (macrophage, lactate dehydrogenase, nitric oxide) were apparently more in the BAL fluid of those with lung involvement than in those without, though the arsenic content did not differ significantly. CONCLUSION: Chronic arsenic poisoning causes pulmonary involvement, predominantly obstructive, the degree of which worsens with increasing degree of arsenic toxicity. Inflammation, rather than direct toxicity, appears to be the underlying mechanism.","Pulmonary involvement in chronic arsenic poisoning from drinking contaminated ground-waterAbs: OBJECTIVES: Chronic arsenic poisoning, due to ingestion of contaminated ground-water, is a major public health problem in West Bengal. It causes multiorgan damage. The present study attempts to objectively investigate the pulmonary involvement by examining the lung function. The nature of lung changes was also evaluated. MATERIAL AND METHODS: One hundred and seven subjects with (cases) and 52 subjects without (controls) chronic arsenic poisoning were examined by spirometry. Forced expiratory volume-I second (FEVI), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were measured. Bronchoalveolar lavage (BAL) was performed in five cases with and five cases without pulmonary involvement. RESULTS: Thirty three (30.8%) cases and four (7.6%) controls (p<0.01) had respiratory involvement. The pattern of involvement in cases was: obstructive- 20(68.9%) (including three (10%) with bronchiectasis), restrictive- 1(3.5%), mixed- 8(27.6%), malignancy- 4(12.1%) (adenocarcinoma-I, squamous cell- 2, undifferentiated- I). FEVI (69.7+/-25.9 [n=105] vs 83.7+/-15.19 [n=51], p=0.0005), FVC (77.4+/-22.7 [n=105] vs 85.6+/-18.23 [n=51], p=0.025), FEVI/FVC (73.6+/-13.38 [n=105] vs 79.1+/-18.65 [n=52], p=0.007) and PEFR (53.9+/-21.52 [n= 103] vs 67.3+/-18.36 [n=51], p=0.0002) (percent of predicted) were all reduced more in cases compared to controls. Worsening of these parameters correlated with increasing degree of arsenic toxicity. Markers of inflammation (macrophage, lactate dehydrogenase, nitric oxide) were apparently more in the BAL fluid of those with lung involvement than in those without, though the arsenic content did not differ significantly. CONCLUSION: Chronic arsenic poisoning causes pulmonary involvement, predominantly obstructive, the degree of which worsens with increasing degree of arsenic toxicity. Inflammation, rather than direct toxicity, appears to be the underlying mechanism."
312,De Kimpe et al. 1993,More than tenfold increase of arsenic in serum and packed cells of chronic hemodialysis patients," Arsenic concentrations were determined in serum and packed cells of 7 chronic hemodialysis patients, in fresh dialysate and in a heparin solution. The analytical technique was radiochemical neutron activation analysis. The accuracy of the method was tested by the analysis of As in certified reference materials. Patients showed elevated serum and packed cell arsenic concentrations compared with controls (serum, range: 2.3-79.8 ng As/ml, median: 11.5 ng As/ml; versus range: 0.132-4.783 ng As/ml, median: 0.38 ng As/ml; packed cells, range: 2.1-68.4 ng As/g, median: 9.5 ng As/g; versus range: 0.51-14.44 ng As/g, median: 3.17 ng As/g). Arsenic concentrations remained unaltered, before versus after a single hemodialysis treatment. The arsenic contents of serum and packed cells were significantly correlated (n = 7, r = 0.96, p < 0.05). No arsenic could be detected in the heparin solution or in the dialysate.","More than tenfold increase of arsenic in serum and packed cells of chronic hemodialysis patientsAbs: Arsenic concentrations were determined in serum and packed cells of 7 chronic hemodialysis patients, in fresh dialysate and in a heparin solution. The analytical technique was radiochemical neutron activation analysis. The accuracy of the method was tested by the analysis of As in certified reference materials. Patients showed elevated serum and packed cell arsenic concentrations compared with controls (serum, range: 2.3-79.8 ng As/ml, median: 11.5 ng As/ml; versus range: 0.132-4.783 ng As/ml, median: 0.38 ng As/ml; packed cells, range: 2.1-68.4 ng As/g, median: 9.5 ng As/g; versus range: 0.51-14.44 ng As/g, median: 3.17 ng As/g). Arsenic concentrations remained unaltered, before versus after a single hemodialysis treatment. The arsenic contents of serum and packed cells were significantly correlated (n = 7, r = 0.96, p < 0.05). No arsenic could be detected in the heparin solution or in the dialysate."
313,Jiang et al. 2003,Interaction of trivalent arsenicals with metallothionein," Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data are available on arsenic-containing proteins in biological systems. This study reports on arsenic interaction with metallothionein and established binding stoichiometries between metallothionein and the recently discovered trivalent metabolites of arsenic metabolism. Size exclusion chromatography with inductively coupled plasma mass spectrometry analysis of reaction mixtures between trivalent arsenicals and metallothionein clearly demonstrated the formation of complexes of arsenic with metallothionein. Analysis of the complexes using electrospray quadrupole time-of-flight tandem mass spectrometry revealed the detailed binding stoichiometry between arsenic and the 20 Cys residues in the metallothionein molecule. Inorganic arsenite (As(III)) and its two trivalent methylation metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), readily bind with metallothionein. Each metallothionein molecule could bind with up to six As(III), 10 MMA(III), and 20 DMA(III) molecules, consistent with the coordination chemistry of these arsenicals. The findings on arsenic interaction with proteins are useful for a better understanding of arsenic health effects.","Interaction of trivalent arsenicals with metallothioneinAbs: Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data are available on arsenic-containing proteins in biological systems. This study reports on arsenic interaction with metallothionein and established binding stoichiometries between metallothionein and the recently discovered trivalent metabolites of arsenic metabolism. Size exclusion chromatography with inductively coupled plasma mass spectrometry analysis of reaction mixtures between trivalent arsenicals and metallothionein clearly demonstrated the formation of complexes of arsenic with metallothionein. Analysis of the complexes using electrospray quadrupole time-of-flight tandem mass spectrometry revealed the detailed binding stoichiometry between arsenic and the 20 Cys residues in the metallothionein molecule. Inorganic arsenite (As(III)) and its two trivalent methylation metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), readily bind with metallothionein. Each metallothionein molecule could bind with up to six As(III), 10 MMA(III), and 20 DMA(III) molecules, consistent with the coordination chemistry of these arsenicals. The findings on arsenic interaction with proteins are useful for a better understanding of arsenic health effects."
314,Del Razo et al. 2002,"Arsenic levels in cooked food and assessment of adult dietary intake of arsenic in the Region Lagunera, Mexico"," The aim of this paper is to estimate the levels of arsenic (As) ingestion through cooked foods consumed in an arsenic endemic area and the assessment of their dietary intake of As. The study was conducted in two villages: a population chronically exposed to a high concentration of As via drinking water (410±35 ?g/l) and to a low-exposure group (12±4 ?g/l). A 24-h dietary recall questionnaire was applied to about 25 adult participants in each community. Samples of cooked food, ready for intake, were collected separately from each family's participants. To obtain the As estimate for each food item consumed, the mean quantity of food ingested in grams (wet weight) was calculated and the concentrations of total arsenic (TAs) in each cooked food were determined. The estimations of TAs intake were based on the sum over mean of As ingested from each food item consumed during the 24-h period for each participant. For the estimation of total daily As intake, we summed the mean obtained from food, plain water and hot beverage intakes. The TAs average intakes calculated for low-As-exposure group were 0.94 and 0.76 ?g/kg body weight/day, for both summer and winter exposure scenarios, respectively. These values are 44.7 and 36% of the provisional tolerable daily intake (PTDI) for inorganic arsenic (2.14 ?g/kg body weight/day), established by the World Health Organization (WHO) in 1989. The WHO reference value was obtained on a weekly basis intake estimation assuming an average body weight of 68 kg in adults. In contrast, for the high-exposure group the TAs average intakes were 16.6 and 12.3 ?g/kg body weight/day for summer and winter, respectively. Ingestion via cooked food represented 32.5 and 43.9% of the total daily As intake in the high-exposure group; for summer and winter, respectively. None the less, the bioavailability of As through food can be different than via drinking water.","Arsenic levels in cooked food and assessment of adult dietary intake of arsenic in the Region Lagunera, MexicoAbs: The aim of this paper is to estimate the levels of arsenic (As) ingestion through cooked foods consumed in an arsenic endemic area and the assessment of their dietary intake of As. The study was conducted in two villages: a population chronically exposed to a high concentration of As via drinking water (410±35 ?g/l) and to a low-exposure group (12±4 ?g/l). A 24-h dietary recall questionnaire was applied to about 25 adult participants in each community. Samples of cooked food, ready for intake, were collected separately from each family's participants. To obtain the As estimate for each food item consumed, the mean quantity of food ingested in grams (wet weight) was calculated and the concentrations of total arsenic (TAs) in each cooked food were determined. The estimations of TAs intake were based on the sum over mean of As ingested from each food item consumed during the 24-h period for each participant. For the estimation of total daily As intake, we summed the mean obtained from food, plain water and hot beverage intakes. The TAs average intakes calculated for low-As-exposure group were 0.94 and 0.76 ?g/kg body weight/day, for both summer and winter exposure scenarios, respectively. These values are 44.7 and 36% of the provisional tolerable daily intake (PTDI) for inorganic arsenic (2.14 ?g/kg body weight/day), established by the World Health Organization (WHO) in 1989. The WHO reference value was obtained on a weekly basis intake estimation assuming an average body weight of 68 kg in adults. In contrast, for the high-exposure group the TAs average intakes were 16.6 and 12.3 ?g/kg body weight/day for summer and winter, respectively. Ingestion via cooked food represented 32.5 and 43.9% of the total daily As intake in the high-exposure group; for summer and winter, respectively. None the less, the bioavailability of As through food can be different than via drinking water."
315,Coronado-Gonzalez et al. 2007,Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico," Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values 126 mg/100 ml (7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied, subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5–104 ?g/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic.","Inorganic arsenic exposure and type 2 diabetes mellitus in MexicoAbs: Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values 126 mg/100 ml (7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied, subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5–104 ?g/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic."
316,Josyula et al. 2006,Environmental arsenic exposure and sputum metalloproteinase concentrations," Exposure to arsenic in drinking water is associated with an increased rate of lung cancer. The objective of this study was to determine whether arsenic exposure at relatively low concentrations (approximately 20 microg/L) is associated with changes in biomarkers of lung inflammation, as measured by the ratio of sputum metalloproteinase and antiproteinase activity. A total of 73 subjects residing in Ajo and Tucson, Arizona were recruited for this cross-sectional study. Tap water and first morning void urine were analyzed for arsenic. Matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in induced sputum. Household tap water arsenic levels in Ajo (20.3+/-3.7 microg/L) were higher than in those Tucson (4.0+/-2.3 microg/L), as were mean urinary total inorganic arsenic levels (29.1+/-20.4 and 11.0+/-12.0 microg/L, respectively). Log-normalized MMP-2, MMP-9, and TIMP-1 concentrations in sputum were not significantly different between towns. However, after adjusting for town, asthma, diabetes, urinary monomethylarsonic acid/inorganic arsenic, and smoking history, total urinary arsenic was negatively associated with MMP-2 and TIMP-1 levels in sputum and positively associated with the ratio of MMP-2/TIMP-1 and MMP-9/TIMP-1 in sputum. Increased sputum proteinase/antiproteinase activity suggests a potential toxic mechanism for low-level arsenic exposure.","Environmental arsenic exposure and sputum metalloproteinase concentrationsAbs: Exposure to arsenic in drinking water is associated with an increased rate of lung cancer. The objective of this study was to determine whether arsenic exposure at relatively low concentrations (approximately 20 microg/L) is associated with changes in biomarkers of lung inflammation, as measured by the ratio of sputum metalloproteinase and antiproteinase activity. A total of 73 subjects residing in Ajo and Tucson, Arizona were recruited for this cross-sectional study. Tap water and first morning void urine were analyzed for arsenic. Matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in induced sputum. Household tap water arsenic levels in Ajo (20.3+/-3.7 microg/L) were higher than in those Tucson (4.0+/-2.3 microg/L), as were mean urinary total inorganic arsenic levels (29.1+/-20.4 and 11.0+/-12.0 microg/L, respectively). Log-normalized MMP-2, MMP-9, and TIMP-1 concentrations in sputum were not significantly different between towns. However, after adjusting for town, asthma, diabetes, urinary monomethylarsonic acid/inorganic arsenic, and smoking history, total urinary arsenic was negatively associated with MMP-2 and TIMP-1 levels in sputum and positively associated with the ratio of MMP-2/TIMP-1 and MMP-9/TIMP-1 in sputum. Increased sputum proteinase/antiproteinase activity suggests a potential toxic mechanism for low-level arsenic exposure."
317,Ding et al. 2005,Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing ROS and RNS generation in human keratinocytes," Arsenic is a naturally occurring element that is present in food, soil, and water. Inorganic arsenic can accumulate in human skin and is associated with increased risk of skin cancer. Oxidative stress due to arsenic exposure is proposed as one potential mode of carcinogenic action. The purpose of this study is to investigate the specific reactive oxygen and nitrogen species that are responsible for the arsenic-induced oxidative damage to DNA and protein. Our results demonstrated that exposure of human keratinocytes to trivalent arsenite caused the generation of 8-hydroxyl-2'-deoxyguanine (8-OHdG) and 3-nitrotyrosine (3-NT) in a concentration- and time-dependent manner. Pentavalent arsenate had similar effects, but to a significantly less extent. The observed oxidative damage can be suppressed by pre-treating cells with specific antioxidants. Furthermore, we found that pre-treating cells with Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), or with 5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphinato iron (III) chloride (FeTMPyP), a decomposition catalyst of peroxynitrite, suppressed the generation of both 8-OHdG and 3-NT, which indicated that peroxynitrite, a product of the reaction of nitric oxide and superoxide, played an important role in arsenic-induced oxidative damage to both DNA and protein. These findings highlight the involvement of peroxynitrite in the molecular mechanism underlying arsenic-induced human skin carcinogenesis.","Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing ROS and RNS generation in human keratinocytesAbs: Arsenic is a naturally occurring element that is present in food, soil, and water. Inorganic arsenic can accumulate in human skin and is associated with increased risk of skin cancer. Oxidative stress due to arsenic exposure is proposed as one potential mode of carcinogenic action. The purpose of this study is to investigate the specific reactive oxygen and nitrogen species that are responsible for the arsenic-induced oxidative damage to DNA and protein. Our results demonstrated that exposure of human keratinocytes to trivalent arsenite caused the generation of 8-hydroxyl-2'-deoxyguanine (8-OHdG) and 3-nitrotyrosine (3-NT) in a concentration- and time-dependent manner. Pentavalent arsenate had similar effects, but to a significantly less extent. The observed oxidative damage can be suppressed by pre-treating cells with specific antioxidants. Furthermore, we found that pre-treating cells with Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), or with 5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphinato iron (III) chloride (FeTMPyP), a decomposition catalyst of peroxynitrite, suppressed the generation of both 8-OHdG and 3-NT, which indicated that peroxynitrite, a product of the reaction of nitric oxide and superoxide, played an important role in arsenic-induced oxidative damage to both DNA and protein. These findings highlight the involvement of peroxynitrite in the molecular mechanism underlying arsenic-induced human skin carcinogenesis."
318,Dopp et al. 2005,Forced uptake of trivalent and pentavalent methylated and inorganic arsenic and its cyto-/genotoxicity in fibroblasts and hepatoma cells," Mammals are able to convert inorganic arsenic to mono-, di-, and trimethylated metabolites. In previous studies we have shown that the trivalent organoarsenic compounds are more toxic than their inorganic counterparts and that the toxicity is associated with the cellular uptake of the arsenicals. In the present study, we investigated cyto-/genotoxic effects of the arsenic compounds arsenate [As(i)(V)], arsenite [As(i)(III)], monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], dimethylarsinous acid [DMA(III)], and trimethylarsine oxide [TMAO(V)] after an extended exposure time (24 h) and compared the uptake capabilities of fibroblasts (CHO-9 cells: Chinese hamster ovary) used for genotoxicity studies, with those of hepatic cells (Hep G2: hepatoma cell-line). To find out whether the arsenic compounds are bound to membranes or if they are present in the cytosol, the amount of arsenic was measured in whole-cell extracts and in membrane-removed cell extracts by inductively coupled plasma-mass spectrometry (ICP-MS). In addition, we forced the cellular uptake of the arsenic compounds into CHO-9 cells by electroporation and measured the intracellular arsenic concentrations before and after this procedure. Our results show that organic and inorganic arsenicals are taken up to a higher degree by fibroblasts compared to hepatoma cells. The arsenic metabolite DMA(III) was the most membrane permeable species in both cell lines and induced strong genotoxic effects in CHO-9 cells after an exposure time of 24 h. The uptake of all other arsenic species was relatively low (<1% by Hep G2 and <4% by CHO cells), but was dose-dependent. Electroporation increased the intracellular arsenic levels as well as the number of induced MN in CHO-9 cells. With the exception of As(i)(III) and DMA(III) in CHO-9 cells, the tested arsenic compounds were not bound to cell membranes, but were present in the cytosol. This may indicate the existence of DMA(III)-specific exporter proteins as are known for As(i)(III). Our results indicate that the uptake capabilities of arsenic compounds are highly dependent upon the cell type. It may be hypothesized that the arsenic-induced genotoxic effects observed in fibroblasts are due to the high uptake of arsenicals into this cell type. This may explain the high susceptibility of skin fibroblasts to arsenic exposure.","Forced uptake of trivalent and pentavalent methylated and inorganic arsenic and its cyto-/genotoxicity in fibroblasts and hepatoma cellsAbs: Mammals are able to convert inorganic arsenic to mono-, di-, and trimethylated metabolites. In previous studies we have shown that the trivalent organoarsenic compounds are more toxic than their inorganic counterparts and that the toxicity is associated with the cellular uptake of the arsenicals. In the present study, we investigated cyto-/genotoxic effects of the arsenic compounds arsenate [As(i)(V)], arsenite [As(i)(III)], monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], dimethylarsinous acid [DMA(III)], and trimethylarsine oxide [TMAO(V)] after an extended exposure time (24 h) and compared the uptake capabilities of fibroblasts (CHO-9 cells: Chinese hamster ovary) used for genotoxicity studies, with those of hepatic cells (Hep G2: hepatoma cell-line). To find out whether the arsenic compounds are bound to membranes or if they are present in the cytosol, the amount of arsenic was measured in whole-cell extracts and in membrane-removed cell extracts by inductively coupled plasma-mass spectrometry (ICP-MS). In addition, we forced the cellular uptake of the arsenic compounds into CHO-9 cells by electroporation and measured the intracellular arsenic concentrations before and after this procedure. Our results show that organic and inorganic arsenicals are taken up to a higher degree by fibroblasts compared to hepatoma cells. The arsenic metabolite DMA(III) was the most membrane permeable species in both cell lines and induced strong genotoxic effects in CHO-9 cells after an exposure time of 24 h. The uptake of all other arsenic species was relatively low (<1% by Hep G2 and <4% by CHO cells), but was dose-dependent. Electroporation increased the intracellular arsenic levels as well as the number of induced MN in CHO-9 cells. With the exception of As(i)(III) and DMA(III) in CHO-9 cells, the tested arsenic compounds were not bound to cell membranes, but were present in the cytosol. This may indicate the existence of DMA(III)-specific exporter proteins as are known for As(i)(III). Our results indicate that the uptake capabilities of arsenic compounds are highly dependent upon the cell type. It may be hypothesized that the arsenic-induced genotoxic effects observed in fibroblasts are due to the high uptake of arsenicals into this cell type. This may explain the high susceptibility of skin fibroblasts to arsenic exposure."
319,Karagas et al. 2001,Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study," Arsenic is a known carcinogen specifically linked to skin cancer occurrence in regions with highly contaminated drinking water or in individuals who took arsenic-containing medicines. Presently, it is unknown whether such effects occur at environmental levels found in the United States. To address this question, the authors used data collected on 587 basal cell and 284 squamous cell skin cancer cases and 524 controls interviewed as part of a case-control study conducted in New Hampshire between 1993 and 1996. Arsenic was determined in toenail clippings using instrumental neutron activation analysis. The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were close to unity in all but the highest category. Among individuals with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI: 0.74, 2.81) for BCC, compared with those with concentrations at or below the median. While the risks of SCC and BCC did not appear elevated at the toenail arsenic concentrations detected in most study subjects, the authors cannot exclude the possibility of a dose-related increase at the highest levels of exposure experienced in the New Hampshire population.","Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control studyAbs: Arsenic is a known carcinogen specifically linked to skin cancer occurrence in regions with highly contaminated drinking water or in individuals who took arsenic-containing medicines. Presently, it is unknown whether such effects occur at environmental levels found in the United States. To address this question, the authors used data collected on 587 basal cell and 284 squamous cell skin cancer cases and 524 controls interviewed as part of a case-control study conducted in New Hampshire between 1993 and 1996. Arsenic was determined in toenail clippings using instrumental neutron activation analysis. The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were close to unity in all but the highest category. Among individuals with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI: 0.74, 2.81) for BCC, compared with those with concentrations at or below the median. While the risks of SCC and BCC did not appear elevated at the toenail arsenic concentrations detected in most study subjects, the authors cannot exclude the possibility of a dose-related increase at the highest levels of exposure experienced in the New Hampshire population."
320,Karagas et al. 2004,Incidence of transitional cell carcinoma of the bladder and arsenic exposure in New Hampshire," Arsenic is a known bladder carcinogen and populations exposed to high arsenic levels in their water supply have reported elevated bladder cancer mortality and incidence rates. To examine the effects of lower levels of arsenic exposure on bladder cancer incidence, we conducted a case-control study in New Hampshire, USA where levels above 10 micro/l are commonly found in private wells.<br /><br /> We studied 383 cases of transitional cell carcinoma of the bladder cancer, newly diagnosed between July 1, 1994 and June 30, 1998 and 641 general population controls. Individual exposure to arsenic was determined in toenail clippings using instrumental neutron activation analysis.<br /><br /> Among smokers, an elevated odds ratio (OR) for bladder cancer was observed for the uppermost category of arsenic (OR: 2.17, 95% CI: 0.92-5.11 for greater than 0.330 mcg/g compared to less than 0.06 micro/g). Among never smokers, there was no association between arsenic and bladder cancer risk.<br /><br /> These, and other data, suggest that ingestion of low to moderate arsenic levels may affect bladder cancer incidence, and that cigarette smoking may act as a co-carcinogen.","Incidence of transitional cell carcinoma of the bladder and arsenic exposure in New HampshireAbs: Arsenic is a known bladder carcinogen and populations exposed to high arsenic levels in their water supply have reported elevated bladder cancer mortality and incidence rates. To examine the effects of lower levels of arsenic exposure on bladder cancer incidence, we conducted a case-control study in New Hampshire, USA where levels above 10 micro/l are commonly found in private wells.<br /><br /> We studied 383 cases of transitional cell carcinoma of the bladder cancer, newly diagnosed between July 1, 1994 and June 30, 1998 and 641 general population controls. Individual exposure to arsenic was determined in toenail clippings using instrumental neutron activation analysis.<br /><br /> Among smokers, an elevated odds ratio (OR) for bladder cancer was observed for the uppermost category of arsenic (OR: 2.17, 95% CI: 0.92-5.11 for greater than 0.330 mcg/g compared to less than 0.06 micro/g). Among never smokers, there was no association between arsenic and bladder cancer risk.<br /><br /> These, and other data, suggest that ingestion of low to moderate arsenic levels may affect bladder cancer incidence, and that cigarette smoking may act as a co-carcinogen."
321,Kazi et al. 2008,The correlation of arsenic levels in drinking water with the biological samples of skin disorders," Arsenic (As) poisoning has become a worldwide public health concern. The skin is quite sensitive to As and skin lesions are the most common and earliest nonmalignant effects associated to chronic As exposure. In 2005–2007, a survey was carried out on surface and groundwater arsenic contamination and relationships between As exposure via the drinking water and related adverse health effects (melanosis and keratosis) on villagers resides on the banks of Manchar lake, southern part of Sindh, Pakistan. We screened the population from arsenic-affected villages, 61 to 73% population were identified patients suffering from chronic arsenic toxicity. The effects of As toxicity via drinking water were estimated by biological samples (scalp hair and blood) of adults (males and females), have or have not skin problem (n=187). The referent samples of both genders were also collected from the areas having low level of As (b10 ?g/L) in drinking water (n=121). Arsenic concentration in drinking water and biological samples were analyzed using electrothermal atomic absorption spectrometry. The range of arsenic concentrations in lake surface water was 35.2–158 ?g/L, which is 3–15 folds higher than World Health Organization [WHO, 2004. Guidelines for drinking-water quality third ed., WHO Geneva Switzerland.]. It was observed that As concentration in the scalp hair and blood samples were above the range of permissible values 0.034–0.319 ?g As/g for hair and b0.5–4.2 ?g/L for blood. The linear regressions showed good correlations between arsenic concentrations in water versus hair and blood samples of exposed skin diseased subjects (R2=0.852 and 0.718) as compared to non-diseased subjects (R2=0.573 and 0.351), respectively.","The correlation of arsenic levels in drinking water with the biological samples of skin disordersAbs: Arsenic (As) poisoning has become a worldwide public health concern. The skin is quite sensitive to As and skin lesions are the most common and earliest nonmalignant effects associated to chronic As exposure. In 2005–2007, a survey was carried out on surface and groundwater arsenic contamination and relationships between As exposure via the drinking water and related adverse health effects (melanosis and keratosis) on villagers resides on the banks of Manchar lake, southern part of Sindh, Pakistan. We screened the population from arsenic-affected villages, 61 to 73% population were identified patients suffering from chronic arsenic toxicity. The effects of As toxicity via drinking water were estimated by biological samples (scalp hair and blood) of adults (males and females), have or have not skin problem (n=187). The referent samples of both genders were also collected from the areas having low level of As (b10 ?g/L) in drinking water (n=121). Arsenic concentration in drinking water and biological samples were analyzed using electrothermal atomic absorption spectrometry. The range of arsenic concentrations in lake surface water was 35.2–158 ?g/L, which is 3–15 folds higher than World Health Organization [WHO, 2004. Guidelines for drinking-water quality third ed., WHO Geneva Switzerland.]. It was observed that As concentration in the scalp hair and blood samples were above the range of permissible values 0.034–0.319 ?g As/g for hair and b0.5–4.2 ?g/L for blood. The linear regressions showed good correlations between arsenic concentrations in water versus hair and blood samples of exposed skin diseased subjects (R2=0.852 and 0.718) as compared to non-diseased subjects (R2=0.573 and 0.351), respectively."
322,Kile and Christiani 2008,Environmental arsenic exposure and diabetes,0,Environmental arsenic exposure and diabetesAbs:0
323,Kile et al. 2009,Variability in biomarkers of arsenic exposure and metabolism in adults over time," Background: Urinary arsenic metabolites (UAs) are used as biomarkers of exposure and metabolism. O b jectives: To characterize inter- and intraindividual variability in UAs in healthy individuals. Methods: In a longitudinal study conducted in Bangladesh, we collected water and spot urine samples from 196 participants every 3 months for 2 years. Water arsenic (As) was measured by inductively coupled plasma–mass spectrometry and urinary As [arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were detected using high-performance liquid chromatography–hydride-generated atomic absorption spectrometry. We used linear mixed-effects models to compute variance components and evaluate the association between UAs and selected factors. R esults: The concentrations of UAs were fairly reproducible within individuals, with intraclass correlation coefficients (ICCs) of 0.41, 0.35, 0.47, and 0.49 for inorganic As (InAs), MMA, DMA, and total urinary As (TUA). However, when expressed as a ratio, the percent InAs (%InAs), %MMA, and %DMA were poorly reproducible within individuals, with ICCs of 0.16, 0.16, and 0.17, respectively. Arsenic metabolism was significantly associated with sex, exposure, age, smoking, chewing betel nut, urinary creatinine, and season. Specificity and sensitivity analyses showed that a single urine sample adequately classified a participant’s urinary As profile as high or low, but TUA had only moderate specificity for correctly classifying drinking water exposures. C onclusions: Epidemiologic studies should use both urinary As concentrations and the relative proportion of UAs to minimize measurement error and to facilitate interpretation of factors that influence As metabolism.","Variability in biomarkers of arsenic exposure and metabolism in adults over timeAbs: Background: Urinary arsenic metabolites (UAs) are used as biomarkers of exposure and metabolism. O b jectives: To characterize inter- and intraindividual variability in UAs in healthy individuals. Methods: In a longitudinal study conducted in Bangladesh, we collected water and spot urine samples from 196 participants every 3 months for 2 years. Water arsenic (As) was measured by inductively coupled plasma–mass spectrometry and urinary As [arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were detected using high-performance liquid chromatography–hydride-generated atomic absorption spectrometry. We used linear mixed-effects models to compute variance components and evaluate the association between UAs and selected factors. R esults: The concentrations of UAs were fairly reproducible within individuals, with intraclass correlation coefficients (ICCs) of 0.41, 0.35, 0.47, and 0.49 for inorganic As (InAs), MMA, DMA, and total urinary As (TUA). However, when expressed as a ratio, the percent InAs (%InAs), %MMA, and %DMA were poorly reproducible within individuals, with ICCs of 0.16, 0.16, and 0.17, respectively. Arsenic metabolism was significantly associated with sex, exposure, age, smoking, chewing betel nut, urinary creatinine, and season. Specificity and sensitivity analyses showed that a single urine sample adequately classified a participant’s urinary As profile as high or low, but TUA had only moderate specificity for correctly classifying drinking water exposures. C onclusions: Epidemiologic studies should use both urinary As concentrations and the relative proportion of UAs to minimize measurement error and to facilitate interpretation of factors that influence As metabolism."
324,Kile et al. 2005,"Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water"," Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (Asin) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 Mg As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dosedependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (b = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (b = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between Asin exposure and toenail Asin content.","Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking waterAbs: Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (Asin) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 Mg As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dosedependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (b = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (b = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between Asin exposure and toenail Asin content."
325,Kile et al. 2007,Dietary arsenic exposure in Bangladesh," BACKGROUND: Millions of people in Bangladesh are at risk of chronic arsenic toxicity from drinking contaminated groundwater, but little is known about diet as an additional source of As exposure. METHODS: We employed a duplicate diet survey to quantify daily As intake in 47 women residing in Pabna, Bangladesh. All samples were analyzed for total As, and a subset of 35 samples were measured for inorganic arsenic (iAs) using inductively coupled plasma mass spectrometry equipped with a dynamic reaction cell. RESULTS: Median daily total As intake was 48 ?g As/day [interquartile range (IQR), 33–67) from food and 4 ?g As/day (IQR, 2–152) from drinking water. On average, iAs comprised 82% of the total As detected in dietary samples. After adjusting for the estimated inorganic fraction, 34% [95% confidence interval (CI), 21–49%] of all participants exceeded the World Health Organization’s provisional tolerable daily intake (PTDI) of 2.1 ?g As/kg-day. Two of the 33 women who used a well with < 50 ?g As/L exceeded this recommendation. CONCLUSIONS: When drinking water concentrations exceeded the Bangladesh drinking water standard of 50 ?g As/L, ingested water was the dominant source of exposure. However, as drinking water As concentrations decrease, the relative contribution of dietary As sources becomes more important to ingested dose. The combined intake from both diet and drinking water can cause some individuals to exceed the PTDI in spite of using a tube well that contains < 50 ?g As/L.","Dietary arsenic exposure in BangladeshAbs: BACKGROUND: Millions of people in Bangladesh are at risk of chronic arsenic toxicity from drinking contaminated groundwater, but little is known about diet as an additional source of As exposure. METHODS: We employed a duplicate diet survey to quantify daily As intake in 47 women residing in Pabna, Bangladesh. All samples were analyzed for total As, and a subset of 35 samples were measured for inorganic arsenic (iAs) using inductively coupled plasma mass spectrometry equipped with a dynamic reaction cell. RESULTS: Median daily total As intake was 48 ?g As/day [interquartile range (IQR), 33–67) from food and 4 ?g As/day (IQR, 2–152) from drinking water. On average, iAs comprised 82% of the total As detected in dietary samples. After adjusting for the estimated inorganic fraction, 34% [95% confidence interval (CI), 21–49%] of all participants exceeded the World Health Organization’s provisional tolerable daily intake (PTDI) of 2.1 ?g As/kg-day. Two of the 33 women who used a well with < 50 ?g As/L exceeded this recommendation. CONCLUSIONS: When drinking water concentrations exceeded the Bangladesh drinking water standard of 50 ?g As/L, ingested water was the dominant source of exposure. However, as drinking water As concentrations decrease, the relative contribution of dietary As sources becomes more important to ingested dose. The combined intake from both diet and drinking water can cause some individuals to exceed the PTDI in spite of using a tube well that contains < 50 ?g As/L."
326,Ettinger et al. 2009,Maternal arsenic exposure and impaired glucose tolerance during pregnancy,"<div>&nbsp;Background: Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives: We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods: Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results: Arsenic concentrations ranged from 0.2 to 24.1 mg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (&gt; 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions: Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD.</div>","Maternal arsenic exposure and impaired glucose tolerance during pregnancyAbs:<div>&nbsp;Background: Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives: We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods: Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results: Arsenic concentrations ranged from 0.2 to 24.1 mg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (&gt; 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions: Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD.</div>"
327,Mazumder et al. 2005,Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water," Background: Arsenic is a unique human carcinogen in that it causes lung cancer by exposure through ingestion (in drinking water) as well as through inhalation. Less is known about nonmalignant pulmonary disease after exposure to arsenic in drinking water. Methods: We recruited 108 subjects with arsenic-caused skin lesions and 150 subjects without lesions from a population survey of over 7000 people in an arsenic-exposed region in West Bengal, India. Thirty-eight study participants who reported at least 2 years of chronic cough underwent high-resolution computed tomography (CT); these scans were read by investigators in India and the United States without knowledge of the presence or absence of skin lesions. Results: The mean (± standard deviation) bronchiectasis severity score was 3.4 (± 3.6) in the 27 participants with skin lesions and 0.9 (± 1.6) in the 11 participants without these lesions. In subjects who reported chronic cough, CT evidence of bronchiectasis was found in 18 (67%) participants with skin lesions and 3 (27%) subjects without skin lesions. Overall, subjects with arsenic-caused skin lesions had a 10-fold increased prevalence of bronchiectasis compared with subjects who did not have skin lesions (adjusted odds ratio = 10; 95% confidence interval = 2.7-37). Conclusions: These results suggest that, in addition to being a cause of lung cancer, ingestion of high concentrations of arsenic in drinking water may be a cause of bronchiectasis.","Bronchiectasis in persons with skin lesions resulting from arsenic in drinking waterAbs: Background: Arsenic is a unique human carcinogen in that it causes lung cancer by exposure through ingestion (in drinking water) as well as through inhalation. Less is known about nonmalignant pulmonary disease after exposure to arsenic in drinking water. Methods: We recruited 108 subjects with arsenic-caused skin lesions and 150 subjects without lesions from a population survey of over 7000 people in an arsenic-exposed region in West Bengal, India. Thirty-eight study participants who reported at least 2 years of chronic cough underwent high-resolution computed tomography (CT); these scans were read by investigators in India and the United States without knowledge of the presence or absence of skin lesions. Results: The mean (± standard deviation) bronchiectasis severity score was 3.4 (± 3.6) in the 27 participants with skin lesions and 0.9 (± 1.6) in the 11 participants without these lesions. In subjects who reported chronic cough, CT evidence of bronchiectasis was found in 18 (67%) participants with skin lesions and 3 (27%) subjects without skin lesions. Overall, subjects with arsenic-caused skin lesions had a 10-fold increased prevalence of bronchiectasis compared with subjects who did not have skin lesions (adjusted odds ratio = 10; 95% confidence interval = 2.7-37). Conclusions: These results suggest that, in addition to being a cause of lung cancer, ingestion of high concentrations of arsenic in drinking water may be a cause of bronchiectasis."
328,Fangstrom et al. 2008,Breast-feeding protects against arsenic exposure in Bangladeshi infants," BACKGROUND: Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. AIM: Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. METHODS: We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. RESULTS: Arsenic concentrations in breast-milk samples were low (median, 1 microg/kg; range, 0.25-19 microg/kg), despite high arsenic exposures via drinking water (10-1,100 microg/L in urine and 2-40 microg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 microg/L; range, 0.3-29 microg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 microg/L (median 1.9 microg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. CONCLUSION: Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic.","Breast-feeding protects against arsenic exposure in Bangladeshi infantsAbs: BACKGROUND: Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. AIM: Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. METHODS: We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. RESULTS: Arsenic concentrations in breast-milk samples were low (median, 1 microg/kg; range, 0.25-19 microg/kg), despite high arsenic exposures via drinking water (10-1,100 microg/L in urine and 2-40 microg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 microg/L; range, 0.3-29 microg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 microg/L (median 1.9 microg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. CONCLUSION: Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic."
329,Kimura et al. 2006,Evaluation of urinary 8-hydroxydeoxyguanine in healthy japanese people," The urinary concentration of 8-hydroxydeoxyguanine (8-0HdG), which is a biomarker of oxidative DNA damage, was measured in 248 healthy Japanese, and its correlations with life style, urinary metal elements, serum antioxidants, and other plasma or serum factors were investigated. The mean urinary concentration of 8-0HdG was 15.2±5.71 ng/mg creatinine. Mean urinary 8-0HdG was not signiiicantly different in terms of age «45, ?-45), gender, smoking (no, <20, ?-20), and alcohol consumption (no, occasionally, sometimes and usually). Moreover, multiple regression analysis showed a signi[icant association between urinary 8-0HdG and urinary arsenic (As) or chromium (Cr), and a tendency for association between the former and aluminum (AI) and nickel (Ni). Age, gender and plasma or serum factors including antioxidants, lipid peroxide, HbAlc, BUN, and iron did not show such an association. The present study suggests that natural exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative DNA damage in healthy people under usual environmental management. Therefore, the measurement of urinary metals such as As, Ni and Cr is prerequisite for the study of the relationship between urinary 8-0HdG and other variable factors.","Evaluation of urinary 8-hydroxydeoxyguanine in healthy japanese peopleAbs: The urinary concentration of 8-hydroxydeoxyguanine (8-0HdG), which is a biomarker of oxidative DNA damage, was measured in 248 healthy Japanese, and its correlations with life style, urinary metal elements, serum antioxidants, and other plasma or serum factors were investigated. The mean urinary concentration of 8-0HdG was 15.2±5.71 ng/mg creatinine. Mean urinary 8-0HdG was not signiiicantly different in terms of age «45, ?-45), gender, smoking (no, <20, ?-20), and alcohol consumption (no, occasionally, sometimes and usually). Moreover, multiple regression analysis showed a signi[icant association between urinary 8-0HdG and urinary arsenic (As) or chromium (Cr), and a tendency for association between the former and aluminum (AI) and nickel (Ni). Age, gender and plasma or serum factors including antioxidants, lipid peroxide, HbAlc, BUN, and iron did not show such an association. The present study suggests that natural exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative DNA damage in healthy people under usual environmental management. Therefore, the measurement of urinary metals such as As, Ni and Cr is prerequisite for the study of the relationship between urinary 8-0HdG and other variable factors."
330,Ferreccio et al. 2000,Lung cancer and arsenic concentrations in drinking water in Chile," Cities in northern Chile had arsenic concentrations of 860 microg/liter in drinking water in the period 1958-1970. Concentrations have since been reduced to 40 microg/liter. We investigated the relation between lung cancer and arsenic in drinking water in northern Chile in a case-control study involving patients diagnosed with lung cancer between 1994 and 1996 and frequency-matched hospital controls. The study identified 152 lung cancer cases and 419 controls. Participants were interviewed regarding drinking water sources, cigarette smoking, and other variables. Logistic regression analysis revealed a clear trend in lung cancer odds ratios and 95% confidence intervals (CIs) with increasing concentration of arsenic in drinking water, as follows: 1, 1.6 (95% CI = 0.5-5.3), 3.9 (95% CI = 1.2-12.3), 5.2 (95% CI = 2.3-11.7), and 8.9 (95% CI = 4.0-19.6), for arsenic concentrations ranging from less than 10 microg/liter to a 65-year average concentration of 200-400 microg/liter. There was evidence of synergy between cigarette smoking and ingestion of arsenic in drinking water; the odds ratio for lung cancer was 32.0 (95% CI = 7.2-198.0) among smokers exposed to more than 200 microg/liter of arsenic in drinking water (lifetime average) compared with nonsmokers exposed to less than 50 microg/liter. This study provides strong evidence that ingestion of inorganic arsenic is associated with human lung cancer.","Lung cancer and arsenic concentrations in drinking water in ChileAbs: Cities in northern Chile had arsenic concentrations of 860 microg/liter in drinking water in the period 1958-1970. Concentrations have since been reduced to 40 microg/liter. We investigated the relation between lung cancer and arsenic in drinking water in northern Chile in a case-control study involving patients diagnosed with lung cancer between 1994 and 1996 and frequency-matched hospital controls. The study identified 152 lung cancer cases and 419 controls. Participants were interviewed regarding drinking water sources, cigarette smoking, and other variables. Logistic regression analysis revealed a clear trend in lung cancer odds ratios and 95% confidence intervals (CIs) with increasing concentration of arsenic in drinking water, as follows: 1, 1.6 (95% CI = 0.5-5.3), 3.9 (95% CI = 1.2-12.3), 5.2 (95% CI = 2.3-11.7), and 8.9 (95% CI = 4.0-19.6), for arsenic concentrations ranging from less than 10 microg/liter to a 65-year average concentration of 200-400 microg/liter. There was evidence of synergy between cigarette smoking and ingestion of arsenic in drinking water; the odds ratio for lung cancer was 32.0 (95% CI = 7.2-198.0) among smokers exposed to more than 200 microg/liter of arsenic in drinking water (lifetime average) compared with nonsmokers exposed to less than 50 microg/liter. This study provides strong evidence that ingestion of inorganic arsenic is associated with human lung cancer."
331,Fischer et al. 2006,Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous mice," Exposure to inorganic arsenic in drinking water is linked to cancer in humans, but the mechanism of arsenic-induced cancer is not clear. Arsenic is not a powerful point mutagen, but can cause chromosome malsegregation and mitotic recombination, two events that can cause loss of tumor suppressor alleles and thereby contribute to the evolution of cancerous cells. To determine whether arsenic increases the frequency of allele loss due to either malsegregation or mitotic recombination in vivo, Aprt(+/-) hybrid mice were exposed to sodium arsenite (10 mg/L) in their drinking water for 10 weeks. To determine whether arsenic enhances the action of a known mutagen, half of the arsenic-treated mice were exposed to benzo[a]pyrene (BaP) for 8 weeks by skin painting (500 nmoles/week). Cells were taken from painted dorsal skin and cultured in the presence of 2,6-diaminopurine (DAP), to select colonies lacking adenosine phosphoribosyl transferase (Aprt) activity. The frequency of DAP-resistant (DAP(r)) colonies varied substantially within the treatment groups, but there was no significant difference between the groups. Analysis of DNA from DAP(r) colonies suggested that mitotic recombination contributed to the loss of wild-type Aprt allele. Whether arsenic or BaP enhanced or diminished the frequency of this process could not be deduced from these data.","Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous miceAbs: Exposure to inorganic arsenic in drinking water is linked to cancer in humans, but the mechanism of arsenic-induced cancer is not clear. Arsenic is not a powerful point mutagen, but can cause chromosome malsegregation and mitotic recombination, two events that can cause loss of tumor suppressor alleles and thereby contribute to the evolution of cancerous cells. To determine whether arsenic increases the frequency of allele loss due to either malsegregation or mitotic recombination in vivo, Aprt(+/-) hybrid mice were exposed to sodium arsenite (10 mg/L) in their drinking water for 10 weeks. To determine whether arsenic enhances the action of a known mutagen, half of the arsenic-treated mice were exposed to benzo[a]pyrene (BaP) for 8 weeks by skin painting (500 nmoles/week). Cells were taken from painted dorsal skin and cultured in the presence of 2,6-diaminopurine (DAP), to select colonies lacking adenosine phosphoribosyl transferase (Aprt) activity. The frequency of DAP-resistant (DAP(r)) colonies varied substantially within the treatment groups, but there was no significant difference between the groups. Analysis of DNA from DAP(r) colonies suggested that mitotic recombination contributed to the loss of wild-type Aprt allele. Whether arsenic or BaP enhanced or diminished the frequency of this process could not be deduced from these data."
332,Fischer et al. 2005,Co-mutagenic activity of arsenic and benzo[a]pyrene in mouse skin," Exposure to inorganic arsenic in drinking water is linked to skin, lung and bladder cancer in humans. The mechanism of arsenic-induced cancer is not clear, but exposure to arsenic and polycyclic arylhydrocarbons (PAH) is more carcinogenic than exposure to either type of carcinogen alone. Arsenic can also generate reactive oxygen species, suggesting that oxidation of DNA may play a role in carcinogenesis. Oxidization of guanosines in polyG tracts is known to cause frameshift mutations, and such events can be detected in situ using the G11 placental alkaline phosphatase (PLAP) transgenic mouse model, which reports frameshift mutations in a run of 11 G:C basepairs by generating cells containing heat-resistant alkaline phosphatase activity. PAH can also induce frameshift mutations. In the study described here, FVB/N mice carrying the G11 PLAP transgene were crossed to C57Bl/6 mice. Half of the hybrid mice were given drinking water with sodium arsenite (10 mg/L) for 10 weeks. Half of the arsenic treated mice were also exposed to benzo[a]pyrene (BaP) by skin painting (500 nmol/week) for 8 weeks. Another group of mice was exposed to BaP but not arsenic. The effect on frameshift mutation was assessed by staining sections of skin tissue to detect cells with PLAP activity. Arsenic alone had no significant effect. On average, mice given BaP alone had approximately three times more PLAP-positive (PLAP+) cells. By contrast, mice exposed to both arsenic and BaP exhibited 10-fold more PLAP+ cells in the skin, and these cells were often arranged in large clusters, suggesting derivation from stem cells. Whereas combined treatment produced more PLAP+ cells, stable BaP adduct levels and arsenic burdens were not higher in mice exposed to both agents compared to mice exposed to either one agent or the other.","Co-mutagenic activity of arsenic and benzo[a]pyrene in mouse skinAbs: Exposure to inorganic arsenic in drinking water is linked to skin, lung and bladder cancer in humans. The mechanism of arsenic-induced cancer is not clear, but exposure to arsenic and polycyclic arylhydrocarbons (PAH) is more carcinogenic than exposure to either type of carcinogen alone. Arsenic can also generate reactive oxygen species, suggesting that oxidation of DNA may play a role in carcinogenesis. Oxidization of guanosines in polyG tracts is known to cause frameshift mutations, and such events can be detected in situ using the G11 placental alkaline phosphatase (PLAP) transgenic mouse model, which reports frameshift mutations in a run of 11 G:C basepairs by generating cells containing heat-resistant alkaline phosphatase activity. PAH can also induce frameshift mutations. In the study described here, FVB/N mice carrying the G11 PLAP transgene were crossed to C57Bl/6 mice. Half of the hybrid mice were given drinking water with sodium arsenite (10 mg/L) for 10 weeks. Half of the arsenic treated mice were also exposed to benzo[a]pyrene (BaP) by skin painting (500 nmol/week) for 8 weeks. Another group of mice was exposed to BaP but not arsenic. The effect on frameshift mutation was assessed by staining sections of skin tissue to detect cells with PLAP activity. Arsenic alone had no significant effect. On average, mice given BaP alone had approximately three times more PLAP-positive (PLAP+) cells. By contrast, mice exposed to both arsenic and BaP exhibited 10-fold more PLAP+ cells in the skin, and these cells were often arranged in large clusters, suggesting derivation from stem cells. Whereas combined treatment produced more PLAP+ cells, stable BaP adduct levels and arsenic burdens were not higher in mice exposed to both agents compared to mice exposed to either one agent or the other."
333,Knobeloch et al. 2006,Association of arsenic-contaminated drinking-water with prevalence of skin cancer in Wisconsin's Fox River Valley," During July 2000-January 2002, the Wisconsin Division of Public Health conducted a study in 19 rural townships. A high percentage of private drinking-water wells in these townships contained traces of arsenic. Residents were asked to collect well-water samples and complete a questionnaire regarding residential history, consumption of drinking-water, and family health. In total, 2,233 household wells were tested, and 6,669 residents, aged less than one year to 100 years, provided information on water consumption and health. The well-water arsenic levels ranged from less than 1.0 to 3,100 microg/L. The median arsenic level was 2.0 microg/L. The arsenic levels were below the federal drinking-water standard of 10 microg/L in 80% of the wells, while 11% had an arsenic level of above 20 microg/L. Of residents aged over 35 years, those who had consumed arsenic-contaminated water for at least 10 years were significantly more likely to report a history of skin cancer than others. Tobacco use was also associated with higher rates of skin cancer and appeared to synergize the effect of arsenic on the development of skin cancer.","Association of arsenic-contaminated drinking-water with prevalence of skin cancer in Wisconsin's Fox River ValleyAbs: During July 2000-January 2002, the Wisconsin Division of Public Health conducted a study in 19 rural townships. A high percentage of private drinking-water wells in these townships contained traces of arsenic. Residents were asked to collect well-water samples and complete a questionnaire regarding residential history, consumption of drinking-water, and family health. In total, 2,233 household wells were tested, and 6,669 residents, aged less than one year to 100 years, provided information on water consumption and health. The well-water arsenic levels ranged from less than 1.0 to 3,100 microg/L. The median arsenic level was 2.0 microg/L. The arsenic levels were below the federal drinking-water standard of 10 microg/L in 80% of the wells, while 11% had an arsenic level of above 20 microg/L. Of residents aged over 35 years, those who had consumed arsenic-contaminated water for at least 10 years were significantly more likely to report a history of skin cancer than others. Tobacco use was also associated with higher rates of skin cancer and appeared to synergize the effect of arsenic on the development of skin cancer."
334,Franzblau and Lilis 1989,Acute arsenic intoxication from environmental arsenic exposure," Reports of acute arsenic poisoning arising from environmental exposure are rare. Two cases of acute arsenic intoxication resulting from ingestion of contaminated well water are described. These patients experienced a variety of problems: acute gastrointestinal symptoms, central and peripheral neurotoxicity, bone marrow suppression, hepatic toxicity, and mild mucous membrane and cutaneous changes. Although located adjacent to an abandoned mine, the well water had been tested for microorganisms only and was found to be ""safe."" Regulations for testing of water from private wells for fitness to drink are frequently nonexistent, or only mandate biologic tests for microorganisms. Well water, particularly in areas near mining activity, should be tested for metals.","Acute arsenic intoxication from environmental arsenic exposureAbs: Reports of acute arsenic poisoning arising from environmental exposure are rare. Two cases of acute arsenic intoxication resulting from ingestion of contaminated well water are described. These patients experienced a variety of problems: acute gastrointestinal symptoms, central and peripheral neurotoxicity, bone marrow suppression, hepatic toxicity, and mild mucous membrane and cutaneous changes. Although located adjacent to an abandoned mine, the well water had been tested for microorganisms only and was found to be ""safe."" Regulations for testing of water from private wells for fitness to drink are frequently nonexistent, or only mandate biologic tests for microorganisms. Well water, particularly in areas near mining activity, should be tested for metals."
335,Frazer 2005,Metal attraction: an ironclad solution to arsenic contamination?," Inorganic arsenic-the more acutely toxic form of this metalloid element-contaminates drinking water supplies around the world. In the United States, the most serious arsenic contamination occurs in the West, Midwest, Southwest, and Northeast; as many as 20 million people-many getting their water from unregulated private wells-may be exposed to excess arsenic in their drinking water. In Bangladesh, it's estimated that as many as 40 million people may be suffering from arsenic poisoning; contaminated drinking water is also a problem in many other countries, including Argentina, China, Chile, Ghana, Hungary, India, and Mexico.","Metal attraction: an ironclad solution to arsenic contamination?Abs: Inorganic arsenic-the more acutely toxic form of this metalloid element-contaminates drinking water supplies around the world. In the United States, the most serious arsenic contamination occurs in the West, Midwest, Southwest, and Northeast; as many as 20 million people-many getting their water from unregulated private wells-may be exposed to excess arsenic in their drinking water. In Bangladesh, it's estimated that as many as 40 million people may be suffering from arsenic poisoning; contaminated drinking water is also a problem in many other countries, including Argentina, China, Chile, Ghana, Hungary, India, and Mexico."
336,Kozul et al. 2009,Low dose arsenic compromises the immune response to influenza A infection in vivo," Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.<br /><br /> We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.<br /><br /> In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.<br /><br /> Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.<br /><br /> Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.","Low dose arsenic compromises the immune response to influenza A infection in vivoAbs: Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.<br /><br /> We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.<br /><br /> In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.<br /><br /> Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.<br /><br /> Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies."
337,Kreiss et al. 1983,Neurologic evaluation of a population exposed to arsenic in Alaskan well water," One hundred forty-seven persons exposed to arsenic from well water were evaluated by neurologic examination and nerve conduction studies. Total arsenic concentrations in well water ranged from 1 to 4781 micrograms/L and from 6 to 4964 micrograms/L in urine; a calculated index of arsenic ingestion ranged from 1 to 4521 micrograms/day. No dose-response relationship existed between arsenic ingestion and symptoms or physical findings compatible with peripheral neuropathy. Five of six persons with symptoms or physical findings suggestive of sensory neuropathy had normal nerve conduction velocities. Thirteen persons with elevated arsenic ingestion but no signs or symptoms of neuropathy had one or more abnormal nerve conduction velocities. No dose-response relationship, however, existed between arsenic ingestion and nerve conduction velocities. The authors concluded that arsenic ingestion from well water at the concentrations found in this Alaskan community did not result in clinical or subclinical neuropathy.","Neurologic evaluation of a population exposed to arsenic in Alaskan well waterAbs: One hundred forty-seven persons exposed to arsenic from well water were evaluated by neurologic examination and nerve conduction studies. Total arsenic concentrations in well water ranged from 1 to 4781 micrograms/L and from 6 to 4964 micrograms/L in urine; a calculated index of arsenic ingestion ranged from 1 to 4521 micrograms/day. No dose-response relationship existed between arsenic ingestion and symptoms or physical findings compatible with peripheral neuropathy. Five of six persons with symptoms or physical findings suggestive of sensory neuropathy had normal nerve conduction velocities. Thirteen persons with elevated arsenic ingestion but no signs or symptoms of neuropathy had one or more abnormal nerve conduction velocities. No dose-response relationship, however, existed between arsenic ingestion and nerve conduction velocities. The authors concluded that arsenic ingestion from well water at the concentrations found in this Alaskan community did not result in clinical or subclinical neuropathy."
338,Krishnamohan et al. 2007,Urinary arsenic methylation and porphyrin profile of C57Bl/6J mice chronically exposed to sodium arsenate," Arsenic interferes with the function of enzymes responsible for haem biosynthesis leading to alteration in the porphyrin profile. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg As(V)/L as sodium arsenate ad libitum for 24 months. 24 h pooled urine samples were collected bimonthly for urinary arsenic methylation and porphyrin analyses by HPLC-ICP-MS and HPLC respectively. The levels of total arsenic were significantly dose related except for the 2nd month interval. No significant differences in the urinary arsenic methylation pattern between control and test groups were observed. Coproporphyrin I (Copro I) showed a significant dose-response relationship after 12, 14 and 20 months of exposure. Significant differences in the levels of coproporphyrin III (Copro III) were observed in the 8th month in 250 and 500 microg/L treatment groups and the dose-response pattern was maintained after 10 and 12 months. Our results suggest that urinary arsenic is a useful biomarker for internal dose, and that urinary coproporphyrin can be used as an early warning biomarker of effects before the onset of cancer.","Urinary arsenic methylation and porphyrin profile of C57Bl/6J mice chronically exposed to sodium arsenateAbs: Arsenic interferes with the function of enzymes responsible for haem biosynthesis leading to alteration in the porphyrin profile. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg As(V)/L as sodium arsenate ad libitum for 24 months. 24 h pooled urine samples were collected bimonthly for urinary arsenic methylation and porphyrin analyses by HPLC-ICP-MS and HPLC respectively. The levels of total arsenic were significantly dose related except for the 2nd month interval. No significant differences in the urinary arsenic methylation pattern between control and test groups were observed. Coproporphyrin I (Copro I) showed a significant dose-response relationship after 12, 14 and 20 months of exposure. Significant differences in the levels of coproporphyrin III (Copro III) were observed in the 8th month in 250 and 500 microg/L treatment groups and the dose-response pattern was maintained after 10 and 12 months. Our results suggest that urinary arsenic is a useful biomarker for internal dose, and that urinary coproporphyrin can be used as an early warning biomarker of effects before the onset of cancer."
339,Fujihara et al. 2007,Population differences in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene polymorphism detected by using genotyping method," Arsenic poisoning from drinking groundwater is a serious problem, particularly in developing Asian countries. Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. Recently, a single nucleotide polymorphism (SNPs; rs17885947, M287T (T860C)) in the AS3MT gene was shown to be related to enzyme activity and considered to be related to genetic susceptibility to arsenic. In the present study, a useful genotyping method for M287T was developed using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Applying this method, the genotype distribution of M287T in Ovambo (n=185), Turkish (n=191), Mongolian (n=233), Korean (n=200), and Japanese (n=370) populations were investigated. The mutation frequencies in Asian populations were relatively lower than those of African and Caucasian populations, including those from previous studies: the frequencies of mutation in the Mongolian, Korean, and Japanese populations were 0.040, 0.010, and 0.010, respectively. In the course of this study, a PCR-based genotyping method that is inexpensive and does not require specialized equipment was developed. This method could be applied to a large number of residents at risk for arsenic poisoning.","Population differences in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene polymorphism detected by using genotyping methodAbs: Arsenic poisoning from drinking groundwater is a serious problem, particularly in developing Asian countries. Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. Recently, a single nucleotide polymorphism (SNPs; rs17885947, M287T (T860C)) in the AS3MT gene was shown to be related to enzyme activity and considered to be related to genetic susceptibility to arsenic. In the present study, a useful genotyping method for M287T was developed using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Applying this method, the genotype distribution of M287T in Ovambo (n=185), Turkish (n=191), Mongolian (n=233), Korean (n=200), and Japanese (n=370) populations were investigated. The mutation frequencies in Asian populations were relatively lower than those of African and Caucasian populations, including those from previous studies: the frequencies of mutation in the Mongolian, Korean, and Japanese populations were 0.040, 0.010, and 0.010, respectively. In the course of this study, a PCR-based genotyping method that is inexpensive and does not require specialized equipment was developed. This method could be applied to a large number of residents at risk for arsenic poisoning."
340,Gamble et al. 2005,"Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh"," Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = ?0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = ?0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = ?0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = ?0.45 for males, p < 0.0001; ?0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.","Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in BangladeshAbs: Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = ?0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = ?0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = ?0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = ?0.45 for males, p < 0.0001; ?0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high."
341,Kwok et al. 2006,Arsenic in drinking-water and reproductive health outcomes: A study of participants in the bangladesh integrated nutrition programme," This study examined 2,006 pregnant women chronically exposed to a range of naturally-occurring concentrations of arsenic in drinking-water in three upazilas in Bangladesh to find out relationships between arsenic exposure and selected reproductive health outcomes. While there was a small but statistically significant association between arsenic exposure and birth-defects (odds ratio=1.005, 95% confidence interval 1.001-1.010), other outcomes, such as stillbirth, low birth-weight, childhood stunting, and childhood under-weight, were not associated with arsenic exposure. It is possible that the association between arsenic exposure from drinking-water and birth-defects may be a statistical anomaly due to the small number of birth-defects observed. Future studies should look more closely at birth-defects, especially neural tube defects, to elucidate any potential health effects associated with arsenic exposure from drinking-water. Further, given the knowledge that serious health effects can result from chronic arsenic exposure, efforts to find alternatives of safe drinking-water for the population must continue.","Arsenic in drinking-water and reproductive health outcomes: A study of participants in the bangladesh integrated nutrition programmeAbs: This study examined 2,006 pregnant women chronically exposed to a range of naturally-occurring concentrations of arsenic in drinking-water in three upazilas in Bangladesh to find out relationships between arsenic exposure and selected reproductive health outcomes. While there was a small but statistically significant association between arsenic exposure and birth-defects (odds ratio=1.005, 95% confidence interval 1.001-1.010), other outcomes, such as stillbirth, low birth-weight, childhood stunting, and childhood under-weight, were not associated with arsenic exposure. It is possible that the association between arsenic exposure from drinking-water and birth-defects may be a statistical anomaly due to the small number of birth-defects observed. Future studies should look more closely at birth-defects, especially neural tube defects, to elucidate any potential health effects associated with arsenic exposure from drinking-water. Further, given the knowledge that serious health effects can result from chronic arsenic exposure, efforts to find alternatives of safe drinking-water for the population must continue."
342,La Porte 2005,Mytilus trossulus hsp70 as a biomarker for arsenic exposure in the marine environment: Laboratory and real-world results," The highly conserved heat shock protein 70 (hsp70) is induced by heat and chemical toxins, particularly heavy metals such as arsenic (As). The use of Mytilus trossulus (bay mussel) hsp70 as a 'screening' biomarker for marine heavy metals contamination was assessed. Some studies have found high hsp70 sensitivity to heavy metals, while others have found the opposite. Few studies have realistically used low heavy metals exposures, and fewer have used real-world contamination exposures. Clean sub-tidal mussels from the Puget Sound, Washington State (WA), USA, were acclimatized for 2 weeks and exposed for 24 h to As-spiked seawater (n=9) or to contaminated seawater from an arsenical pesticide plant in Tacoma, WA (n=10) followed by a Western blot for hsp70. Hsp70 inductions were insignificant at 10 microg l(-1) As(III), but were strong at 100 microg l(-1) (p&lt;0.05) and 1000 microg l(-1) (p&lt;0.01), with the induction threshold estimated at 30-50 microg l(-1) As(III). Hsp70 induction roughly correlated with arsenical toxicity, with As(III) &gt; As(V) &gt; (CH(3))(2)As(V). Altogether, the inter-individual variability of hsp70 levels tends to mask inductions at low As concentrations, making it a crude toxicity biomarker. In addressing this problem, the following options could prove promising: (1) pre- or post-stressing specimens for greater hsp70 sensitivity, (2) use of internal protein controls such as actin, (3) use of hsp70-reporter gene constructs, and (4) detection with hsp60, heme oxygenase-1, metallothionein, CYP450, MXR or GPx.","Mytilus trossulus hsp70 as a biomarker for arsenic exposure in the marine environment: Laboratory and real-world resultsAbs: The highly conserved heat shock protein 70 (hsp70) is induced by heat and chemical toxins, particularly heavy metals such as arsenic (As). The use of Mytilus trossulus (bay mussel) hsp70 as a 'screening' biomarker for marine heavy metals contamination was assessed. Some studies have found high hsp70 sensitivity to heavy metals, while others have found the opposite. Few studies have realistically used low heavy metals exposures, and fewer have used real-world contamination exposures. Clean sub-tidal mussels from the Puget Sound, Washington State (WA), USA, were acclimatized for 2 weeks and exposed for 24 h to As-spiked seawater (n=9) or to contaminated seawater from an arsenical pesticide plant in Tacoma, WA (n=10) followed by a Western blot for hsp70. Hsp70 inductions were insignificant at 10 microg l(-1) As(III), but were strong at 100 microg l(-1) (p&lt;0.05) and 1000 microg l(-1) (p&lt;0.01), with the induction threshold estimated at 30-50 microg l(-1) As(III). Hsp70 induction roughly correlated with arsenical toxicity, with As(III) &gt; As(V) &gt; (CH(3))(2)As(V). Altogether, the inter-individual variability of hsp70 levels tends to mask inductions at low As concentrations, making it a crude toxicity biomarker. In addressing this problem, the following options could prove promising: (1) pre- or post-stressing specimens for greater hsp70 sensitivity, (2) use of internal protein controls such as actin, (3) use of hsp70-reporter gene constructs, and (4) detection with hsp60, heme oxygenase-1, metallothionein, CYP450, MXR or GPx."
343,Garcia-Chavez et al. 2007,Functional and morphological effects of repeated sodium arsenite exposure on rat peripheral sensory nerves," Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy. To better understand the functional and morphological consequences of iAs exposure, we examined the electrophysiological and histological characteristics of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels in the peripheral nerves of exposed animals were about 150 times greater than those in controls. Lipid peroxidation was also increased in iAs-exposed animals. Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also showed a trend towards a decreased CAP area ( approximately 35%). These electrophysiological changes were consistent with histological alterations such as a approximately 56% decrease in myelin thickness. In addition, the perimeter and transverse area of axons were reduced to 29% and 45% of control, respectively. Our results suggest that accumulation of As produced by iAs exposure induces oxidative damage, severe demyelination, and other morphological alterations in axons of peripheral nerves. These changes may, in turn, induce changes in the generation and propagation of action potentials in peripheral nerves, leading to decreased transmission of information from peripheral sensory organs to the central nervous system.","Functional and morphological effects of repeated sodium arsenite exposure on rat peripheral sensory nervesAbs: Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy. To better understand the functional and morphological consequences of iAs exposure, we examined the electrophysiological and histological characteristics of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels in the peripheral nerves of exposed animals were about 150 times greater than those in controls. Lipid peroxidation was also increased in iAs-exposed animals. Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also showed a trend towards a decreased CAP area ( approximately 35%). These electrophysiological changes were consistent with histological alterations such as a approximately 56% decrease in myelin thickness. In addition, the perimeter and transverse area of axons were reduced to 29% and 45% of control, respectively. Our results suggest that accumulation of As produced by iAs exposure induces oxidative damage, severe demyelination, and other morphological alterations in axons of peripheral nerves. These changes may, in turn, induce changes in the generation and propagation of action potentials in peripheral nerves, leading to decreased transmission of information from peripheral sensory organs to the central nervous system."
344,Garcia-Medina et al. 2007,Conditioned flavor aversion and brain Fos expression following exposure to arsenic," Recent advances in the knowledge of the cellular effects of arsenic have provided insights into the molecular mechanisms of arsenic-associated carcinogenesis, immunotoxicity and cardiovascular disease. In the present experiments we tested the hypothesis that the arrival of arsenic to the gastrointestinal (GI) tract is detected by the gut-brain axis, which includes hindbrain and forebrain nuclei activated by GI stimulation. As a marker of neuronal activation we measured Fos expression using immunohistochemistry. Because Fos expression in these nuclei is closely linked to the development of conditioned flavor aversion (CFA) we also tested the effect of arsenic on CFA. Our experiments indicate that arsenic ingestion is readily detected by the brain, as shown by increased Fos expression after oral administration of arsenic. Furthermore, the vagus nerve, which supplies information from the GI tract to the brain, is not involved in this response because a complete subdiaphragmatic vagotomy did not reduce the effect of arsenic on brain Fos expression, but enhanced this response. In parallel, arsenic ingestion is associated with a robust, dose-dependent CFA, which started at doses as low as 0.1 mg/kg body weight. In summary, these data indicate that arsenic given by oral administration is detected by the brain in low concentrations, and activates specific nuclei, which might trigger behavioral responses, such as CFA.","Conditioned flavor aversion and brain Fos expression following exposure to arsenicAbs: Recent advances in the knowledge of the cellular effects of arsenic have provided insights into the molecular mechanisms of arsenic-associated carcinogenesis, immunotoxicity and cardiovascular disease. In the present experiments we tested the hypothesis that the arrival of arsenic to the gastrointestinal (GI) tract is detected by the gut-brain axis, which includes hindbrain and forebrain nuclei activated by GI stimulation. As a marker of neuronal activation we measured Fos expression using immunohistochemistry. Because Fos expression in these nuclei is closely linked to the development of conditioned flavor aversion (CFA) we also tested the effect of arsenic on CFA. Our experiments indicate that arsenic ingestion is readily detected by the brain, as shown by increased Fos expression after oral administration of arsenic. Furthermore, the vagus nerve, which supplies information from the GI tract to the brain, is not involved in this response because a complete subdiaphragmatic vagotomy did not reduce the effect of arsenic on brain Fos expression, but enhanced this response. In parallel, arsenic ingestion is associated with a robust, dose-dependent CFA, which started at doses as low as 0.1 mg/kg body weight. In summary, these data indicate that arsenic given by oral administration is detected by the brain in low concentrations, and activates specific nuclei, which might trigger behavioral responses, such as CFA."
345,Gault et al. 2008,"Arsenic in hair and nails of individuals exposed to arsenic-rich groundwaters in Kandal province, Cambodia"," The health implications of the consumption of high arsenic groundwater in Bangladesh and West Bengal are well-documented, however, little is known about the level of arsenic exposure elsewhere in Southeast Asia, where widespread exploitation of groundwater resources is less well established. We measured the arsenic concentrations of nail and hair samples collected from residents of Kandal province, Cambodia, an area recently identified to host arsenic-rich groundwaters, in order to evaluate the extent of arsenic exposure. Nail and hair arsenic concentrations ranged from 0.20 to 6.50 microg g(-1) (n=70) and 0.10 to 7.95 microg g(-1) (n=40), respectively, in many cases exceeding typical baseline levels. The arsenic content of the groundwater used for drinking water purposes (0.21-943 microg L(-1) (n=31)) was positively correlated with both nail (r=0.74, p<0.0001) and hair (r=0.86, p<0.0001) arsenic concentrations. In addition, the nail and hair samples collected from inhabitants using groundwater that exceeded the Cambodian drinking water legal limit of 50 microg L(-1) arsenic contained significantly more arsenic than those of individuals using groundwater containing <50 microg L(-1) arsenic. X-ray absorption near edge structure (XANES) spectroscopy suggested that sulfur-coordinated arsenic was the dominant species in the bulk of the samples analysed, with additional varying degrees of As(III)-O character. Tentative linear least squares fitting of the XANES data pointed towards differences in the pattern of arsenic speciation between the nail and hair samples analysed, however, mismatches in sample and standard absorption peak intensity prevented us from unambiguously determining the arsenic species distribution. The good correlation with the groundwater arsenic concentration, allied with the relative ease of sampling such tissues, indicate that the arsenic content of hair and nail samples may be used as an effective biomarker of arsenic intake in this relatively recently exposed population.","Arsenic in hair and nails of individuals exposed to arsenic-rich groundwaters in Kandal province, CambodiaAbs: The health implications of the consumption of high arsenic groundwater in Bangladesh and West Bengal are well-documented, however, little is known about the level of arsenic exposure elsewhere in Southeast Asia, where widespread exploitation of groundwater resources is less well established. We measured the arsenic concentrations of nail and hair samples collected from residents of Kandal province, Cambodia, an area recently identified to host arsenic-rich groundwaters, in order to evaluate the extent of arsenic exposure. Nail and hair arsenic concentrations ranged from 0.20 to 6.50 microg g(-1) (n=70) and 0.10 to 7.95 microg g(-1) (n=40), respectively, in many cases exceeding typical baseline levels. The arsenic content of the groundwater used for drinking water purposes (0.21-943 microg L(-1) (n=31)) was positively correlated with both nail (r=0.74, p<0.0001) and hair (r=0.86, p<0.0001) arsenic concentrations. In addition, the nail and hair samples collected from inhabitants using groundwater that exceeded the Cambodian drinking water legal limit of 50 microg L(-1) arsenic contained significantly more arsenic than those of individuals using groundwater containing <50 microg L(-1) arsenic. X-ray absorption near edge structure (XANES) spectroscopy suggested that sulfur-coordinated arsenic was the dominant species in the bulk of the samples analysed, with additional varying degrees of As(III)-O character. Tentative linear least squares fitting of the XANES data pointed towards differences in the pattern of arsenic speciation between the nail and hair samples analysed, however, mismatches in sample and standard absorption peak intensity prevented us from unambiguously determining the arsenic species distribution. The good correlation with the groundwater arsenic concentration, allied with the relative ease of sampling such tissues, indicate that the arsenic content of hair and nail samples may be used as an effective biomarker of arsenic intake in this relatively recently exposed population."
346,Lamm et al. 2004,Arsenic in drinking water and bladder cancer mortality in the United States: An analysis based on 133 U.S. counties and 30 years of observation," This study analyzes the relationship between arsenic exposure through drinking water and bladder cancer mortality. The county-specific white male bladder cancer mortality data (1950-1979) and county-specific groundwater arsenic concentration data were obtained for 133 U.S. counties known to be exclusively dependent on groundwater for their public drinking water supply. No arsenic-related increase in bladder cancer mortality was found over the exposure range of 3 to 60 microg/L using stratified analysis and regression analyses (both unweighted and weighted by county population and using both mean and median arsenic concentrations). These results, which provide a direct estimate of arsenic-related cancer risk for U.S. residents, exclude the National Research Council's 2001 risk estimate that was based on Southwest Taiwan data and required adjusting for differences between the body mass and water consumption rates of U.S. and Taiwanese residents.","Arsenic in drinking water and bladder cancer mortality in the United States: An analysis based on 133 U.S. counties and 30 years of observationAbs: This study analyzes the relationship between arsenic exposure through drinking water and bladder cancer mortality. The county-specific white male bladder cancer mortality data (1950-1979) and county-specific groundwater arsenic concentration data were obtained for 133 U.S. counties known to be exclusively dependent on groundwater for their public drinking water supply. No arsenic-related increase in bladder cancer mortality was found over the exposure range of 3 to 60 microg/L using stratified analysis and regression analyses (both unweighted and weighted by county population and using both mean and median arsenic concentrations). These results, which provide a direct estimate of arsenic-related cancer risk for U.S. residents, exclude the National Research Council's 2001 risk estimate that was based on Southwest Taiwan data and required adjusting for differences between the body mass and water consumption rates of U.S. and Taiwanese residents."
347,Lamm et al. 2007,"An epidemiologic study of arsenic-related skin disorders and skin cancer and the consumption of arsenic-contaminated well Waters in Huhhot, Inner Mongolia, China", ,"An epidemiologic study of arsenic-related skin disorders and skin cancer and the consumption of arsenic-contaminated well Waters in Huhhot, Inner Mongolia, ChinaAbs: "
348,Germolec et al. 1998,Arsenic enhancement of skin neoplasia by chronic stimulation of growth factors," Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors, such as transforming growth factor (TGF)-a, promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA), a marked increase in the number of skin papillomas occurred in Tg.AC mice, which carry the v-Ha-ras oncogene, that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings, increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and TGF-a mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-a overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter.","Arsenic enhancement of skin neoplasia by chronic stimulation of growth factorsAbs: Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors, such as transforming growth factor (TGF)-a, promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA), a marked increase in the number of skin papillomas occurred in Tg.AC mice, which carry the v-Ha-ras oncogene, that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings, increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and TGF-a mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-a overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter."
349,Lamm et al. 2006,Arsenic cancer risk confounder in southwest Taiwan data set," Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)–endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose–response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 ?g/L (95% confidence interval, 42 to 229 ?g/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose–response relationship with arsenic exposure by separating out township as a confounding factor. Key words: arsenic, blackfoot disease, bladder cancer, cancer risk, confounder, dose–response relationship, southwest Taiwan, threshold model.","Arsenic cancer risk confounder in southwest Taiwan data setAbs: Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)–endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose–response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 ?g/L (95% confidence interval, 42 to 229 ?g/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose–response relationship with arsenic exposure by separating out township as a confounding factor. Key words: arsenic, blackfoot disease, bladder cancer, cancer risk, confounder, dose–response relationship, southwest Taiwan, threshold model."
350,Lamm et al. 2003,Bladder cancer and arsenic exposure: Differences in the two populations enrolled in a study in southwest Taiwan," Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 mg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought. Methods Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so . Underlying data for the Morales et al. study were obtained from the appendix to the NRC report. Bladder cancer mortality rates were calculated from case counts and person-years of observation for each study village. Villages were categorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source. Results The median village well arsenic levels ranged from 350 to 934 mg/L for villages solely dependent on artesian well water and from 10 to 717 mg/L for villages not solely dependent on artesian well water. Bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. Bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources. Conclusions The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be explained either by arsenic acting as a high-dose carcinogen or in artesian well water as a co-carcinogen with some other aspect of artesian well water (possibly humic acid). Arsenic exposure level alone appears to be an insufficient exposure measure to describe the risk of bladder cancer mortality in the BFD-endemic area. Risk analyses that fail to take water source into account are likely to misrepresent the risk characterization, particularly at low arsenic levels.","Bladder cancer and arsenic exposure: Differences in the two populations enrolled in a study in southwest TaiwanAbs: Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 mg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought. Methods Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so . Underlying data for the Morales et al. study were obtained from the appendix to the NRC report. Bladder cancer mortality rates were calculated from case counts and person-years of observation for each study village. Villages were categorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source. Results The median village well arsenic levels ranged from 350 to 934 mg/L for villages solely dependent on artesian well water and from 10 to 717 mg/L for villages not solely dependent on artesian well water. Bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. Bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources. Conclusions The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be explained either by arsenic acting as a high-dose carcinogen or in artesian well water as a co-carcinogen with some other aspect of artesian well water (possibly humic acid). Arsenic exposure level alone appears to be an insufficient exposure measure to describe the risk of bladder cancer mortality in the BFD-endemic area. Risk analyses that fail to take water source into account are likely to misrepresent the risk characterization, particularly at low arsenic levels."
351,Lantz et al. 2007,Pulmonary biomarkers based on alterations in protein expression after exposure to arsenic," OBJECTIVE: Environmental exposure to arsenic results in multiple adverse effects in the lung. Our objective was to identify potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose As and to validate these protein changes in human populations exposed to As. METHODS: Mice were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4 weeks. Proteins in the lung-lining fluid were identified using two-dimensional gel electrophoresis (n = 3) or multidimensional protein identification technology (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were collected from 57 individuals (tap water As ranged from ~ 5 to 20 ppb). Protein levels in sputum were determined by ELISA, and As species were analyzed in first morning void urine. RESULTS: Proteins in mouse lung-lining fluid whose expression was consistently altered by As included glutathione-S-transferase (GST)-omega-1, contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6, and receptor for advanced glycation end products (RAGE). Validation of the putative biomarkers was carried out by evaluating As-induced alterations in RAGE in humans. Regression analysis demonstrated a significant negative correlation (p = 0.016) between sputum levels of RAGE and total urinary inorganic As, similar to results seen in our animal model. CONCLUSION: Combinations of proteomic analyses of animal models followed by specific analysis of human samples provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease.","Pulmonary biomarkers based on alterations in protein expression after exposure to arsenicAbs: OBJECTIVE: Environmental exposure to arsenic results in multiple adverse effects in the lung. Our objective was to identify potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose As and to validate these protein changes in human populations exposed to As. METHODS: Mice were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4 weeks. Proteins in the lung-lining fluid were identified using two-dimensional gel electrophoresis (n = 3) or multidimensional protein identification technology (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were collected from 57 individuals (tap water As ranged from ~ 5 to 20 ppb). Protein levels in sputum were determined by ELISA, and As species were analyzed in first morning void urine. RESULTS: Proteins in mouse lung-lining fluid whose expression was consistently altered by As included glutathione-S-transferase (GST)-omega-1, contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6, and receptor for advanced glycation end products (RAGE). Validation of the putative biomarkers was carried out by evaluating As-induced alterations in RAGE in humans. Regression analysis demonstrated a significant negative correlation (p = 0.016) between sputum levels of RAGE and total urinary inorganic As, similar to results seen in our animal model. CONCLUSION: Combinations of proteomic analyses of animal models followed by specific analysis of human samples provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease."
352,Ghosh et al. 2007,"Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India"," A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.","Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, IndiaAbs: A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic."
353,Ghosh et al. 2007,Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus," The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 microM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of ""IL-4 like factors"" from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.","Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachusAbs: The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 microM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of ""IL-4 like factors"" from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge."
354,Ghosh et al. 2006,Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water," In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity.","Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking waterAbs: In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity."
355,Goessler et al. 1997,Can humans metabolize arsenic compounds to arsenobetaine?," Arsenic compounds were determined in 21 urine samples collected from a male volunteer. The volunteer was exposed to arsenic through either consumption of codfish or inhalation of small amounts of (CH3)3As present in the laboratory air. The arsenic compounds in the urine were separated and quantified with an HPLC-ICP-MS system equipped with a hydraulic high-pressure nebulizer. This method has a determination limit of 0.5 ug As dm-3 urine. To eliminate the influence of the density of the urine, creatinine was determined and all concentrations of arsenic compounds were expressed in ug As g-1 creatinine. The concentrations of arsenite, arsenate and methylarsonic acid in the urine were not influenced by the consumption of seafood. Exposure to trimethylarsine doubled the concentration of arsenate and increased the concentration of methylarsonic acid drastically (0.5 to 5 ug As g-1 creatinine). The concentration of dimethylarsinic acid was elevated after the first consumption of fish (2.8 to 4.3 ug As g-1 creatinine), after the second consumption of fish (4.9 to 26.5 ug As g-1 creatinine) and after exposure to trimethyl- arsine (2.9 to 9.6 ug As g-1 creatinine). As expected, the concentration of arsenobetaine in the urine increased 30- to 50-fold after the first consumption of codfish. Surprisingly, the concentration of arsenobetaine also increased after exposure to trimethylarsine, from a background of approximately 1 ug As g-1 creatinine up to 33.1 ug As g-1 creatinine. Arsenobetaine was detected in all the urine samples investigated. The arsenobetaine in the urine not ascribable to consumed seafood could come from food items of terrestrial origin that - unknown to us - contain arsenobetaine. The possibility that the human body is capable of metabolizing trimethyl- arsine to arsenobetaine must be considered.","Can humans metabolize arsenic compounds to arsenobetaine?Abs: Arsenic compounds were determined in 21 urine samples collected from a male volunteer. The volunteer was exposed to arsenic through either consumption of codfish or inhalation of small amounts of (CH3)3As present in the laboratory air. The arsenic compounds in the urine were separated and quantified with an HPLC-ICP-MS system equipped with a hydraulic high-pressure nebulizer. This method has a determination limit of 0.5 ug As dm-3 urine. To eliminate the influence of the density of the urine, creatinine was determined and all concentrations of arsenic compounds were expressed in ug As g-1 creatinine. The concentrations of arsenite, arsenate and methylarsonic acid in the urine were not influenced by the consumption of seafood. Exposure to trimethylarsine doubled the concentration of arsenate and increased the concentration of methylarsonic acid drastically (0.5 to 5 ug As g-1 creatinine). The concentration of dimethylarsinic acid was elevated after the first consumption of fish (2.8 to 4.3 ug As g-1 creatinine), after the second consumption of fish (4.9 to 26.5 ug As g-1 creatinine) and after exposure to trimethyl- arsine (2.9 to 9.6 ug As g-1 creatinine). As expected, the concentration of arsenobetaine in the urine increased 30- to 50-fold after the first consumption of codfish. Surprisingly, the concentration of arsenobetaine also increased after exposure to trimethylarsine, from a background of approximately 1 ug As g-1 creatinine up to 33.1 ug As g-1 creatinine. Arsenobetaine was detected in all the urine samples investigated. The arsenobetaine in the urine not ascribable to consumed seafood could come from food items of terrestrial origin that - unknown to us - contain arsenobetaine. The possibility that the human body is capable of metabolizing trimethyl- arsine to arsenobetaine must be considered."
356,Adonis et al. 2005,Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic," In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 microg/m3, presently declining to 40 microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure.","Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenicAbs: In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 microg/m3, presently declining to 40 microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure."
357,Adonis et al. 2005,CYP1A1 and GSTM1 genetic polymorphisms in lung cancer populations exposed to arsenic in drinking water," Region II of Chile is the most important copper mining area in the world and it shows the highest lung cancer mortality rate in the country (35/100,000). The population in Antofagasta, the main city of Region II, was exposed from 1958 to 1970 to 860 microg m(-3) arsenic (As) in drinking water and has currently been declining to 40 microg m(-3). Glutathione serves as a reducing agent and glutathione S-transferase (GST) may have an important role in As methylation capacity and body retention. In the current study, the null genotype of GSTM1 and the MspI polymorphism of CYP450 1A1 were investigated in lung cancer patients and in healthy volunteers of Region II. In males, the 2A genotype of MspI represented a highly significant estimated relative lung cancer risk (OR=2.60). Relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habit (OR=2.98). In Region II, the cancer mortality rate for As-associated cancers at least partly might be related to differences in As biotransformation. Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health.","CYP1A1 and GSTM1 genetic polymorphisms in lung cancer populations exposed to arsenic in drinking waterAbs: Region II of Chile is the most important copper mining area in the world and it shows the highest lung cancer mortality rate in the country (35/100,000). The population in Antofagasta, the main city of Region II, was exposed from 1958 to 1970 to 860 microg m(-3) arsenic (As) in drinking water and has currently been declining to 40 microg m(-3). Glutathione serves as a reducing agent and glutathione S-transferase (GST) may have an important role in As methylation capacity and body retention. In the current study, the null genotype of GSTM1 and the MspI polymorphism of CYP450 1A1 were investigated in lung cancer patients and in healthy volunteers of Region II. In males, the 2A genotype of MspI represented a highly significant estimated relative lung cancer risk (OR=2.60). Relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habit (OR=2.98). In Region II, the cancer mortality rate for As-associated cancers at least partly might be related to differences in As biotransformation. Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health."
358,Lee et al. 2006,Defective Î²1-integrins expression in arsenical keratosis and arsenic-treated cultured human keratinocytes," <strong>BACKGROUND: </strong>beta1-integrins, which localize to the basolateral surface of basal keratinocytes, are important in the differentiation control and proliferation of the epidermis. Many cutaneous diseases with perturbed differentiation, including arsenical keratosis, show altered patterns of integrin distribution and expression. Arsenic may induce arsenical keratosis through the differentiation and apoptosis aberration by integrins. The purpose of this study is to investigate the role of integrin and arsenic in the pathogenesis of arsenical keratosis.<br /><br /><strong>METHODS: </strong>Twenty-five specimens obtained from 25 patients with arsenical keratosis disease were studied. Immunohistochemistry staining to beta1, alpha2beta1, or alpha3beta1 integrins was performed in arsenical keratosis and clinically normal perilesional skin. Western blotting was used to assess the expression of integrin beta1 and focal adhesion kinase (FAK) in arsenic-treated cultured keratinocytes.<br /><br /><strong>RESULTS: </strong>A decreased expression of beta1, alpha2beta1, or alpha3beta1 integrins was demonstrated in arsenical keratosis and clinical normal perilesional skin in a large proportion of arsenical keratosis cases studied. The expressions of integrin beta1 and FAK were both decreased in arsenic-treated keratinocytes.<br /><br /><strong>CONCLUSIONS: </strong>Our results suggest that arsenic induces abnormal differentiation in arsenical keratosis via the effects of integrin expression in keratinocytes.","Defective Î²1-integrins expression in arsenical keratosis and arsenic-treated cultured human keratinocytesAbs: <strong>BACKGROUND: </strong>beta1-integrins, which localize to the basolateral surface of basal keratinocytes, are important in the differentiation control and proliferation of the epidermis. Many cutaneous diseases with perturbed differentiation, including arsenical keratosis, show altered patterns of integrin distribution and expression. Arsenic may induce arsenical keratosis through the differentiation and apoptosis aberration by integrins. The purpose of this study is to investigate the role of integrin and arsenic in the pathogenesis of arsenical keratosis.<br /><br /><strong>METHODS: </strong>Twenty-five specimens obtained from 25 patients with arsenical keratosis disease were studied. Immunohistochemistry staining to beta1, alpha2beta1, or alpha3beta1 integrins was performed in arsenical keratosis and clinically normal perilesional skin. Western blotting was used to assess the expression of integrin beta1 and focal adhesion kinase (FAK) in arsenic-treated cultured keratinocytes.<br /><br /><strong>RESULTS: </strong>A decreased expression of beta1, alpha2beta1, or alpha3beta1 integrins was demonstrated in arsenical keratosis and clinical normal perilesional skin in a large proportion of arsenical keratosis cases studied. The expressions of integrin beta1 and FAK were both decreased in arsenic-treated keratinocytes.<br /><br /><strong>CONCLUSIONS: </strong>Our results suggest that arsenic induces abnormal differentiation in arsenical keratosis via the effects of integrin expression in keratinocytes."
359,Lee et al. 2004,Effects and Interactions of low doses of arsenic and UVB on keratinocyte apoptosis," Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions of arsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play a modulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluate the effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Cultured human keratinocytes were treated with sodium arsenite (1 microM) and/or UVB (50 mJ/cm(2)) irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followed by UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysis and BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared to that of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression. In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressed as compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increased in the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activities in UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group. Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenic treatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our results provide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skin and the potential therapeutic role of UVB in arsenic-induced Bowen's disease.","Effects and Interactions of low doses of arsenic and UVB on keratinocyte apoptosisAbs: Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions of arsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play a modulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluate the effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Cultured human keratinocytes were treated with sodium arsenite (1 microM) and/or UVB (50 mJ/cm(2)) irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followed by UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysis and BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared to that of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression. In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressed as compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increased in the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activities in UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group. Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenic treatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our results provide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skin and the potential therapeutic role of UVB in arsenic-induced Bowen's disease."
360,Gordon et al. 2002,In vitro bioavailability of heavy metals in pressure-treated wood dust," Pressure treatment with chromium, copper, and arsenic (CCA) is the most prevalent method for protecting wood used in outdoor construction projects. Although these metals are tightly bound to the wood fibers and are not released under most conditions of use, we examined the bioavailability of metals in CCA pressure-treated wood dust in vitro. Cytotoxicity and metallothionein (MT) mRNA expression were examined in V79 Chinese hamster lung fibroblast cells incubated with respirable-size wood dust generated by sanding CCA-treated and untreated (control) Southern yellow pine. In colony survival studies, increased cytotoxicity (p < 0.05) occurred in V79 cells treated with CCA wood dust (351 +/- 77 microg/ml, mean +/- SE) compared with control wood dust (883 +/- 91 microg/ml). Increased cytotoxicity with CCA wood dust also occurred in an arsenic resistant subline of V79 cells, thus suggesting that arsenic was not responsible for the increased cytotoxicity. Metallothionein mRNA was significantly increased after 48 h of treatment with CCA wood dust compared with control wood dust. Incubation of CCA wood dust in cell culture media resulted in the transfer of copper, but not chromium or arsenic, into the media. Moreover, the treatment of cells with this filtered extract resulted in significantly increased metallothionein mRNA, suggesting that bioavailable copper is responsible for inducing metallothionein mRNA in V79 cells. Thus, these bioassays suggest that metals become bioavailable during in vitro culture of phagocytic V79 cells with CCA wood dust.","In vitro bioavailability of heavy metals in pressure-treated wood dustAbs: Pressure treatment with chromium, copper, and arsenic (CCA) is the most prevalent method for protecting wood used in outdoor construction projects. Although these metals are tightly bound to the wood fibers and are not released under most conditions of use, we examined the bioavailability of metals in CCA pressure-treated wood dust in vitro. Cytotoxicity and metallothionein (MT) mRNA expression were examined in V79 Chinese hamster lung fibroblast cells incubated with respirable-size wood dust generated by sanding CCA-treated and untreated (control) Southern yellow pine. In colony survival studies, increased cytotoxicity (p < 0.05) occurred in V79 cells treated with CCA wood dust (351 +/- 77 microg/ml, mean +/- SE) compared with control wood dust (883 +/- 91 microg/ml). Increased cytotoxicity with CCA wood dust also occurred in an arsenic resistant subline of V79 cells, thus suggesting that arsenic was not responsible for the increased cytotoxicity. Metallothionein mRNA was significantly increased after 48 h of treatment with CCA wood dust compared with control wood dust. Incubation of CCA wood dust in cell culture media resulted in the transfer of copper, but not chromium or arsenic, into the media. Moreover, the treatment of cells with this filtered extract resulted in significantly increased metallothionein mRNA, suggesting that bioavailable copper is responsible for inducing metallothionein mRNA in V79 cells. Thus, these bioassays suggest that metals become bioavailable during in vitro culture of phagocytic V79 cells with CCA wood dust."
361,Guha Mazumder et al. 1988,Chronic arsenic toxicity from drinking tubewell water in rural West Bengal," Hepatic damage caused by chronic exposure to arsenic has been frequently described. Here we report on 13 patients from West Bengal, India, who consumed large amounts of arsenic in drinking water. An epidemiological investigation of the study area showed evidence of chronic arsenical dermatosis and hepatomegaly in 62 (92.5%) of 67 members of families who drank contaminated water (arsenic level, 0.2-2 mg/l). In contrast, only six (6.25%) of 96 persons from the same area who drank safe water (arsenic level, <0.05 mg/l) had non-specific hepatomegaly, while none had skin lesions. Hepatomegaly occurred in all the 13 patients who were studied in detail, although five had splenomegaly. Biopsy of samples of liver from these patients revealed various degrees of fibrosis and expansion of the portal zone that resembled non-cirrhotic portal fibrosis (NCPF).","Chronic arsenic toxicity from drinking tubewell water in rural West BengalAbs: Hepatic damage caused by chronic exposure to arsenic has been frequently described. Here we report on 13 patients from West Bengal, India, who consumed large amounts of arsenic in drinking water. An epidemiological investigation of the study area showed evidence of chronic arsenical dermatosis and hepatomegaly in 62 (92.5%) of 67 members of families who drank contaminated water (arsenic level, 0.2-2 mg/l). In contrast, only six (6.25%) of 96 persons from the same area who drank safe water (arsenic level, <0.05 mg/l) had non-specific hepatomegaly, while none had skin lesions. Hepatomegaly occurred in all the 13 patients who were studied in detail, although five had splenomegaly. Biopsy of samples of liver from these patients revealed various degrees of fibrosis and expansion of the portal zone that resembled non-cirrhotic portal fibrosis (NCPF)."
362,Guo et al. 1997,Arsenic in drinking water and incidence of urinary cancers," The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific.","Arsenic in drinking water and incidence of urinary cancersAbs: The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific."
363,Guo et al. 2001,"Arsenic in drinking water and skin cancers: Cell-type specificity (Taiwan, ROC)"," OBJECTIVE: The association between arsenic ingestion and cancer has been documented for more than a century. Previous studies showed that the carcinogenic effects of arsenic on the urinary system are cell-type specific. To evaluate whether this is also true for skin cancers, we conducted an ecological study in 243 townships in Taiwan. METHODS: The arsenic exposure was assessed on the basis of measurement reports from a previous survey, and cases of skin cancer were identified using the information gathered by the National Cancer Registry Program. We analyzed the data by regression models using multiple variables to describe the exposure status, and an urbanization index was also included in the models to adjust for the effects of urbanization. RESULTS: A total of 2369 patients with skin cancer, comprising 1415 men and 954 women, were registered between 1 January 1980 and 31 December 1989. Among the three major cell types of skin cancer, squamous cell carcinoma and basal cell carcinoma appear to be associated with ingestion of arsenic. Such an association was not observed for malignant melanoma. CONCLUSIONS: The results suggested that the carcinogenicity of arsenic on skin is cell-type specific, which is compatible with the findings in previous studies on urinary cancers.","Arsenic in drinking water and skin cancers: Cell-type specificity (Taiwan, ROC)Abs: OBJECTIVE: The association between arsenic ingestion and cancer has been documented for more than a century. Previous studies showed that the carcinogenic effects of arsenic on the urinary system are cell-type specific. To evaluate whether this is also true for skin cancers, we conducted an ecological study in 243 townships in Taiwan. METHODS: The arsenic exposure was assessed on the basis of measurement reports from a previous survey, and cases of skin cancer were identified using the information gathered by the National Cancer Registry Program. We analyzed the data by regression models using multiple variables to describe the exposure status, and an urbanization index was also included in the models to adjust for the effects of urbanization. RESULTS: A total of 2369 patients with skin cancer, comprising 1415 men and 954 women, were registered between 1 January 1980 and 31 December 1989. Among the three major cell types of skin cancer, squamous cell carcinoma and basal cell carcinoma appear to be associated with ingestion of arsenic. Such an association was not observed for malignant melanoma. CONCLUSIONS: The results suggested that the carcinogenicity of arsenic on skin is cell-type specific, which is compatible with the findings in previous studies on urinary cancers."
364,Guo 2003,The lack of a specific association between arsenic in drinking water and hepatocellular carcinoma," BACKGROUND/AIMS: Liver cancers, particularly angiosarcomas, among patients with arsenic intoxication have been reported for more than half a century. Studies on cancers of urinary system and skin showed the carcinogenic effect of arsenic was cell-type specific. To evaluate whether this is also true for liver cancers, a study was conducted in 243 townships in Taiwan. METHODS: Cases of liver cancer were identified through the National Cancer Registry Program. The distribution of major cell-types was compared between an endemic area of arsenic intoxication, including 5 of the 243 townships, and the rest of the townships. RESULTS: A total of 40,832 patients with liver cancer, including 32,034 men and 8798 women, were diagnosed between January 1, 1980 and December 31, 1999 in the study townships. Distributions of the two major cell-types, hepatocellular carcinoma and cholangiocarcinoma, did not appear to be different between the arsenic intoxication endemic area and the other areas. The rest of the cell-types did not have enough cases to provide stable estimates. CONCLUSIONS: Convincing evidence in the literature has suggested a specific association between angiosarcoma of liver and arsenic ingestion, but the current study did not find such an association for hepatocellular carcinoma, although it is the major cell-type.","The lack of a specific association between arsenic in drinking water and hepatocellular carcinomaAbs: BACKGROUND/AIMS: Liver cancers, particularly angiosarcomas, among patients with arsenic intoxication have been reported for more than half a century. Studies on cancers of urinary system and skin showed the carcinogenic effect of arsenic was cell-type specific. To evaluate whether this is also true for liver cancers, a study was conducted in 243 townships in Taiwan. METHODS: Cases of liver cancer were identified through the National Cancer Registry Program. The distribution of major cell-types was compared between an endemic area of arsenic intoxication, including 5 of the 243 townships, and the rest of the townships. RESULTS: A total of 40,832 patients with liver cancer, including 32,034 men and 8798 women, were diagnosed between January 1, 1980 and December 31, 1999 in the study townships. Distributions of the two major cell-types, hepatocellular carcinoma and cholangiocarcinoma, did not appear to be different between the arsenic intoxication endemic area and the other areas. The rest of the cell-types did not have enough cases to provide stable estimates. CONCLUSIONS: Convincing evidence in the literature has suggested a specific association between angiosarcoma of liver and arsenic ingestion, but the current study did not find such an association for hepatocellular carcinoma, although it is the major cell-type."
365,Lewis et al. 1999,Drinking water arsenic in Utah: A cohort mortality study," The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted.","Drinking water arsenic in Utah: A cohort mortality studyAbs: The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted."
366,Guo 2004,Arsenic level in drinking water and mortality of lung cancer (Taiwan)," OBJECTIVE: Lung cancers have been observed among patients of arsenic intoxication since the 1950s, but data on the dose-response relationship were limited. In order to obtain such data, a study was conducted in ten townships in Taiwan. METHODS: Measurements of arsenic levels in drinking water were available for 138 villages from a census survey conducted by the government. Certificates of deaths that occurred in the villages between January 1, 1971 and December 31, 1990 were reviewed, and 673 male and 405 female mortality cases of lung cancer were identified. Multi-variate regression models were applied to assess associations between arsenic levels in drinking water and mortality of lung cancer using village as the unit. RESULTS: After adjusting for age, arsenic levels above 0.64 mg/l were associated with a significant increase in the mortality of lung cancer in both genders, but no significant effect was observed at lower levels. Post-hoc analyses confirmed such a dose-response relationship. CONCLUSIONS: The results indicate a prominent carcinogenic effect of high arsenic levels in drinking water on the lung and suggest the new 'maximum contaminant level' of 10 micro g/l published by the US Environmental Protection Agency provides sufficient protection against lung cancer. Nonetheless, further studies with exposure data on individuals are warranted to confirm these findings.","Arsenic level in drinking water and mortality of lung cancer (Taiwan)Abs: OBJECTIVE: Lung cancers have been observed among patients of arsenic intoxication since the 1950s, but data on the dose-response relationship were limited. In order to obtain such data, a study was conducted in ten townships in Taiwan. METHODS: Measurements of arsenic levels in drinking water were available for 138 villages from a census survey conducted by the government. Certificates of deaths that occurred in the villages between January 1, 1971 and December 31, 1990 were reviewed, and 673 male and 405 female mortality cases of lung cancer were identified. Multi-variate regression models were applied to assess associations between arsenic levels in drinking water and mortality of lung cancer using village as the unit. RESULTS: After adjusting for age, arsenic levels above 0.64 mg/l were associated with a significant increase in the mortality of lung cancer in both genders, but no significant effect was observed at lower levels. Post-hoc analyses confirmed such a dose-response relationship. CONCLUSIONS: The results indicate a prominent carcinogenic effect of high arsenic levels in drinking water on the lung and suggest the new 'maximum contaminant level' of 10 micro g/l published by the US Environmental Protection Agency provides sufficient protection against lung cancer. Nonetheless, further studies with exposure data on individuals are warranted to confirm these findings."
367,Li et al. 2001,Formamidopyrimidine-DNA glycosylase enhances arsenic-Induced DNA strand breaks in PHA-stimulated and unstimulated human lymphocytes," To confirm that arsenic (As) induces oxidative DNA damage in phytohemagglutinin (PHA)-stimulated and unstimulated human lymphocytes, we used the alkaline comet assay combined with specific enzyme [formamidopyrimidine-DNA glycosylase (FPG)] digestion to measure As-induced base damage. The results showed that the enzyme-sensitive sites were readily detected with the alkaline comet assay after the cells were treated with 10 microM As for 2 hr. The repair patterns observed for FPG-created DNA single strand breaks (SSBs) in As-treated cells were comparable to those in hydrogen peroxide (H(2)O(2))-treated cells. The enzyme-created SSBs, As-induced base damage, were more significant in PHA-stimulated lymphocytes. About 63% and 68% of SSBs induced by As and H(2)O(2), respectively, were repaired in PHA-stimulated lymphocytes by 2-hr repair incubation, but about 34% and 43%, respectively, were repaired in unstimulated cells. About 40% and 49% of base damage induced by As and H(2)O(2), respectively, were repaired in PHA-stimulated lymphocytes, but about 19% and 21%, respectively, were repaired in unstimulated cells. These results indicated that As induced oxidative DNA damage in human lymphocytes at micromolar concentrations. The damaged bases could be chiefly purines or formamidopyrimidines. Like the damage induced by H(2)O(2), As-induced DNA damage was repaired more slowly in unstimulated lymphocytes.","Formamidopyrimidine-DNA glycosylase enhances arsenic-Induced DNA strand breaks in PHA-stimulated and unstimulated human lymphocytesAbs: To confirm that arsenic (As) induces oxidative DNA damage in phytohemagglutinin (PHA)-stimulated and unstimulated human lymphocytes, we used the alkaline comet assay combined with specific enzyme [formamidopyrimidine-DNA glycosylase (FPG)] digestion to measure As-induced base damage. The results showed that the enzyme-sensitive sites were readily detected with the alkaline comet assay after the cells were treated with 10 microM As for 2 hr. The repair patterns observed for FPG-created DNA single strand breaks (SSBs) in As-treated cells were comparable to those in hydrogen peroxide (H(2)O(2))-treated cells. The enzyme-created SSBs, As-induced base damage, were more significant in PHA-stimulated lymphocytes. About 63% and 68% of SSBs induced by As and H(2)O(2), respectively, were repaired in PHA-stimulated lymphocytes by 2-hr repair incubation, but about 34% and 43%, respectively, were repaired in unstimulated cells. About 40% and 49% of base damage induced by As and H(2)O(2), respectively, were repaired in PHA-stimulated lymphocytes, but about 19% and 21%, respectively, were repaired in unstimulated cells. These results indicated that As induced oxidative DNA damage in human lymphocytes at micromolar concentrations. The damaged bases could be chiefly purines or formamidopyrimidines. Like the damage induced by H(2)O(2), As-induced DNA damage was repaired more slowly in unstimulated lymphocytes."
368,Guo et al. 2006,Association between multi-level inorganic arsenic exposure from drinking water and skin lesions in China," Arsenic is one of the most important toxicants in the environment. In Inner Mongolia of China, 300,000 residents are believed to be drinking water containing >50 microg/liter. Skin lesions have been known as the most common consequences resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic-induced skin lesions, it is important to assess the impact of this problem among the target population, and to make future planning. We evaluated the association between multi-levels inorganic arsenic exposure from drinking water and skin lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine and 32 subjects in high (>50 microg/liter) and low (<50 microg/liter) arsenic-affected villages were recruited and had the detailed physical examination with special emphasis on arsenic-related skin lesions. Arsenic exposure was measured for each participant with respect to iAs concentration of primary well and the duration using the well. Arsenic-induced skin lesions including keratosis, pigmentation, and/or depigmentation were diagnosed in 56 and 3 subjects in the two villages, respectively. Logistic regression was conducted to calculate odd ratios of skin lesions associated with arsenic exposure with adjustments for sex, age group, smoking and duration of exposure. A consistent dose-response relationship between arsenic exposure level and skin lesion risk was observed. Compared to those with iAs concentration <50 microg/liter, the adjusted odds ratios of skin lesions for the subjects with 51-99, 100-149 and >150 microg/liter were 33.3% (OR =15.50, 95% CI: 1.53-248.70), 46.7% (OR =16.10, 95% CI: 3.73-69.63) and 55.7% (OR= 25.70, 95% CI: 6.43-102.87), respectively. Duration of using well was not associated with increased risk of skin lesions in this population; (OR =1.68, 95% CI: 0.40-6.91 for 6-15 years, OR = 2.30, 95% CI: 0.58-9.14 for over 15 years) compared with the duration of less than 5 years.","Association between multi-level inorganic arsenic exposure from drinking water and skin lesions in ChinaAbs: Arsenic is one of the most important toxicants in the environment. In Inner Mongolia of China, 300,000 residents are believed to be drinking water containing >50 microg/liter. Skin lesions have been known as the most common consequences resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic-induced skin lesions, it is important to assess the impact of this problem among the target population, and to make future planning. We evaluated the association between multi-levels inorganic arsenic exposure from drinking water and skin lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine and 32 subjects in high (>50 microg/liter) and low (<50 microg/liter) arsenic-affected villages were recruited and had the detailed physical examination with special emphasis on arsenic-related skin lesions. Arsenic exposure was measured for each participant with respect to iAs concentration of primary well and the duration using the well. Arsenic-induced skin lesions including keratosis, pigmentation, and/or depigmentation were diagnosed in 56 and 3 subjects in the two villages, respectively. Logistic regression was conducted to calculate odd ratios of skin lesions associated with arsenic exposure with adjustments for sex, age group, smoking and duration of exposure. A consistent dose-response relationship between arsenic exposure level and skin lesion risk was observed. Compared to those with iAs concentration <50 microg/liter, the adjusted odds ratios of skin lesions for the subjects with 51-99, 100-149 and >150 microg/liter were 33.3% (OR =15.50, 95% CI: 1.53-248.70), 46.7% (OR =16.10, 95% CI: 3.73-69.63) and 55.7% (OR= 25.70, 95% CI: 6.43-102.87), respectively. Duration of using well was not associated with increased risk of skin lesions in this population; (OR =1.68, 95% CI: 0.40-6.91 for 6-15 years, OR = 2.30, 95% CI: 0.58-9.14 for over 15 years) compared with the duration of less than 5 years."
369,Ahmad et al. 2001,Arsenic in drinking water and pregnancy outcomes," We studied a group of women of reproductive age (15-49 years) who were chronically exposed to arsenic through drinking water to identify the pregnancy outcomes in terms of live birth, stillbirth, spontaneous abortion, and preterm birth. We compared pregnancy outcomes of exposed respondents with pregnancy outcomes of women of reproductive age (15-49 years) who were not exposed to arsenic-contaminated water. In a cross-sectional study, we matched the women in both exposed and nonexposed groups for age, socioeconomic status, education, and age at marriage. The total sample size was 192, with 96 women in each group (i.e., exposed and nonexposed). Of the respondents in the exposed group, 98% had been drinking water containing [Greater and equal to] 0.10 mg/L arsenic and 43.8% had been drinking arsenic-contaminated water for 5-10 years. Skin manifestation due to chronic arsenic exposure was present in 22.9% of the respondents. Adverse pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm birth rates were significantly higher in the exposed group than those in the nonexposed group (p = 0.008, p = 0.046, and p = 0.018, respectively).","Arsenic in drinking water and pregnancy outcomesAbs: We studied a group of women of reproductive age (15-49 years) who were chronically exposed to arsenic through drinking water to identify the pregnancy outcomes in terms of live birth, stillbirth, spontaneous abortion, and preterm birth. We compared pregnancy outcomes of exposed respondents with pregnancy outcomes of women of reproductive age (15-49 years) who were not exposed to arsenic-contaminated water. In a cross-sectional study, we matched the women in both exposed and nonexposed groups for age, socioeconomic status, education, and age at marriage. The total sample size was 192, with 96 women in each group (i.e., exposed and nonexposed). Of the respondents in the exposed group, 98% had been drinking water containing [Greater and equal to] 0.10 mg/L arsenic and 43.8% had been drinking arsenic-contaminated water for 5-10 years. Skin manifestation due to chronic arsenic exposure was present in 22.9% of the respondents. Adverse pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm birth rates were significantly higher in the exposed group than those in the nonexposed group (p = 0.008, p = 0.046, and p = 0.018, respectively)."
370,Li et al. 2007,Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh," Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p&lt;or=0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p &lt;or= 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions.","Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in BangladeshAbs: Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p&lt;or=0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p &lt;or= 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions."
371,Hafeman et al. 2005,Association between arsenic exposure and a measure of subclinical sensory neuropathy in Bangladesh," OBJECTIVES: We examined the association between arsenic exposure and peripheral neuropathy in Bangladesh, where the population has been chronically exposed to arsenic in drinking water. METHODS: We conducted a cross-sectional study of 137 subjects derived from a larger cohort. Exposure measures included individual water arsenic concentration, cumulative arsenic index, and urinary arsenic concentration taken at two time points (2001 and 2003). The primary outcome measurement was elevated vibrotactile threshold, as measured by a vibration sensitivity tester (Vibratron II). RESULTS: Arsenic exposure was associated with elevated toe vibration threshold (TVT). Specifically, cumulative arsenic index and urinary arsenic (2001) were both significantly associated with elevated TVT (P = 0.02 and P = 0.009, respectively) after adjustment for age and gender. CONCLUSIONS: Increased arsenic exposure, as measured by both cumulative and urinary measures, was associated with evidence of subclinical sensory neuropathy.","Association between arsenic exposure and a measure of subclinical sensory neuropathy in BangladeshAbs: OBJECTIVES: We examined the association between arsenic exposure and peripheral neuropathy in Bangladesh, where the population has been chronically exposed to arsenic in drinking water. METHODS: We conducted a cross-sectional study of 137 subjects derived from a larger cohort. Exposure measures included individual water arsenic concentration, cumulative arsenic index, and urinary arsenic concentration taken at two time points (2001 and 2003). The primary outcome measurement was elevated vibrotactile threshold, as measured by a vibration sensitivity tester (Vibratron II). RESULTS: Arsenic exposure was associated with elevated toe vibration threshold (TVT). Specifically, cumulative arsenic index and urinary arsenic (2001) were both significantly associated with elevated TVT (P = 0.02 and P = 0.009, respectively) after adjustment for age and gender. CONCLUSIONS: Increased arsenic exposure, as measured by both cumulative and urinary measures, was associated with evidence of subclinical sensory neuropathy."
372,Hall et al. 2006,Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study," Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r=0.85) and with water As (WAs) (r=0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population.","Blood arsenic as a biomarker of arsenic exposure: Results from a prospective studyAbs: Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r=0.85) and with water As (WAs) (r=0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population."
373,Hamadeh et al. 2002,Coordination of altered DNA repair and damage pathways in arsenite-exposed keratinocytes," Human exposure to arsenic, a ubiquitous and toxic environmental pollutant, is associated with an increased incidence of skin cancer. However, the mechanism(s) associated with AsIII-mediated toxicity and carcinogenesis at low levels of exposure remains elusive. Aberrations in cell proliferation, oxidative damage, and DNA-repair fidelity have been implicated in sodium arsenite (AsIII)-mediated carcinogenicity and toxicity, but these events have been examined in isolation in the majority of biological models of arsenic exposure. We hypothesized that the simultaneous interaction of these effects may be important in arsenic-mediated neoplasia in the skin. To evaluate this, normal human epidermal keratinocytes (NHEK) were exposed to nontoxic doses (0.005-5 micro M) of AsIII and monitored for several physiological endpoints at the times when cells were harvested for gene expression measurements (1-24 h). Two-fluor cDNA microarray analyses indicated that AsIII treatment decreased the expression of genes associated with DNA repair (e.g., p53 and Damage-specific DNA-binding protein 2) and increased the expression of genes indicative of the cellular response to oxidative stress (e.g., Superoxide dismutase 1, NAD(P)H quinone oxidoreductase, and Serine/threonine kinase 25). AsIII also modulated the expression of certain transcripts associated with increased cell proliferation (e.g., Cyclin G1, Protein kinase C delta), oncogenes, and genes associated with cellular transformation (e.g., Gro-1 and V-yes). These observations correlated with measurements of cell proliferation and mitotic measurements as AsIII treatment resulted in a dose-dependent increase in cellular mitoses at 24 h and an increase in cell proliferation at 48 h of exposure. Data in this manuscript demonstrates that AsIII exposure simultaneously modulates DNA repair, cell proliferation, and redox-related gene expression in nontransformed, normal NHEK. It is anticipated that data in this report will serve as a foundation for furthering our knowledge of AsIII-regulated gene expression in skin and other tissues and contribute to a better understanding of arsenic toxicity and carcinogenesis.","Coordination of altered DNA repair and damage pathways in arsenite-exposed keratinocytesAbs: Human exposure to arsenic, a ubiquitous and toxic environmental pollutant, is associated with an increased incidence of skin cancer. However, the mechanism(s) associated with AsIII-mediated toxicity and carcinogenesis at low levels of exposure remains elusive. Aberrations in cell proliferation, oxidative damage, and DNA-repair fidelity have been implicated in sodium arsenite (AsIII)-mediated carcinogenicity and toxicity, but these events have been examined in isolation in the majority of biological models of arsenic exposure. We hypothesized that the simultaneous interaction of these effects may be important in arsenic-mediated neoplasia in the skin. To evaluate this, normal human epidermal keratinocytes (NHEK) were exposed to nontoxic doses (0.005-5 micro M) of AsIII and monitored for several physiological endpoints at the times when cells were harvested for gene expression measurements (1-24 h). Two-fluor cDNA microarray analyses indicated that AsIII treatment decreased the expression of genes associated with DNA repair (e.g., p53 and Damage-specific DNA-binding protein 2) and increased the expression of genes indicative of the cellular response to oxidative stress (e.g., Superoxide dismutase 1, NAD(P)H quinone oxidoreductase, and Serine/threonine kinase 25). AsIII also modulated the expression of certain transcripts associated with increased cell proliferation (e.g., Cyclin G1, Protein kinase C delta), oncogenes, and genes associated with cellular transformation (e.g., Gro-1 and V-yes). These observations correlated with measurements of cell proliferation and mitotic measurements as AsIII treatment resulted in a dose-dependent increase in cellular mitoses at 24 h and an increase in cell proliferation at 48 h of exposure. Data in this manuscript demonstrates that AsIII exposure simultaneously modulates DNA repair, cell proliferation, and redox-related gene expression in nontransformed, normal NHEK. It is anticipated that data in this report will serve as a foundation for furthering our knowledge of AsIII-regulated gene expression in skin and other tissues and contribute to a better understanding of arsenic toxicity and carcinogenesis."
374,Hamadeh et al. 1999,Arsenic disrupts cellular levels of p53 and mdm2: A potential mechanism of carcinogenesis," The antitumor protein p53 plays a critical role in DNA repair. Inorganic arsenic exposure is associated with a wide variety of human tumors, particularly of the skin. To investigate how inorganic arsenic might interfere with DNA repair and lead to greater incidence of hyperkeratosis and skin tumors, we exposed human keratinocytes (HaCaT) to environmentally relevant concentrations of arsenite for 14 days. Arsenite reduced p53 levels while concomitantly increasing the p53 regulatory protein mdm2 levels in a dose- and time-dependent manner. We propose the disruption of the p53-mdm2 loop regulating cell cycle arrest as a model for arsenic-related skin carcinogenesis and it may be important in tumors with elevated mdm2 levels.","Arsenic disrupts cellular levels of p53 and mdm2: A potential mechanism of carcinogenesisAbs: The antitumor protein p53 plays a critical role in DNA repair. Inorganic arsenic exposure is associated with a wide variety of human tumors, particularly of the skin. To investigate how inorganic arsenic might interfere with DNA repair and lead to greater incidence of hyperkeratosis and skin tumors, we exposed human keratinocytes (HaCaT) to environmentally relevant concentrations of arsenite for 14 days. Arsenite reduced p53 levels while concomitantly increasing the p53 regulatory protein mdm2 levels in a dose- and time-dependent manner. We propose the disruption of the p53-mdm2 loop regulating cell cycle arrest as a model for arsenic-related skin carcinogenesis and it may be important in tumors with elevated mdm2 levels."
375,Han et al. 2009,Arsenic levels in ground water and cancer incidence in Idaho: An ecologic study," PURPOSE: Long-term exposure to arsenic above 50 microg/L in drinking water has been related to multiple types of cancers. Few epidemiologic studies conducted in the US have detected an association between regional exposures below this level in drinking water and corresponding cancer occurrence rates. This county-level ecologic study evaluates arsenic levels in ground water and its association with targeted cancer incidence in Idaho, where some regions have been found to contain higher arsenic levels. METHODS: Using cancer incidence data (1991-2005) from the Cancer Data Registry of Idaho and arsenic data (1991-2005) from the Idaho Department of Environmental Quality, we calculated the age-adjusted incidence rate for cancers of the urinary bladder, kidney and renal pelvis, liver and bile duct, lung and bronchus, non-Hodgkin's lymphoma (NHL), and all malignant cancers according to arsenic levels in ground water. Multivariate regression analysis was applied to evaluate the relationship between arsenic levels in ground water and cancer incidence. RESULTS: For males, but not for females, age-adjusted incidence for lung cancer and all malignant cancers was significantly higher in the intermediate arsenic counties (2-9 microg/L, n = 16) and the high arsenic counties (>or=10 microg/L, n = 5) compared to the low arsenic counties (<2.0 microg/L, n = 23). When adjusted for race, gender, population density, smoking and body mass index (BMI), no relationship was found between arsenic levels in ground water and cancer incidence. CONCLUSIONS: In this ecological design, exposure to low-level arsenic in ground water is not associated with cancer incidence when adjusting for salient variables. For populations residing in southwestern Idaho, where arsenic has been found to exceed 10 microg/L in ground water, individual risk assessment is required in order to determine whether there is a link between long-term arsenic exposure at these levels and cancer risk.","Arsenic levels in ground water and cancer incidence in Idaho: An ecologic studyAbs: PURPOSE: Long-term exposure to arsenic above 50 microg/L in drinking water has been related to multiple types of cancers. Few epidemiologic studies conducted in the US have detected an association between regional exposures below this level in drinking water and corresponding cancer occurrence rates. This county-level ecologic study evaluates arsenic levels in ground water and its association with targeted cancer incidence in Idaho, where some regions have been found to contain higher arsenic levels. METHODS: Using cancer incidence data (1991-2005) from the Cancer Data Registry of Idaho and arsenic data (1991-2005) from the Idaho Department of Environmental Quality, we calculated the age-adjusted incidence rate for cancers of the urinary bladder, kidney and renal pelvis, liver and bile duct, lung and bronchus, non-Hodgkin's lymphoma (NHL), and all malignant cancers according to arsenic levels in ground water. Multivariate regression analysis was applied to evaluate the relationship between arsenic levels in ground water and cancer incidence. RESULTS: For males, but not for females, age-adjusted incidence for lung cancer and all malignant cancers was significantly higher in the intermediate arsenic counties (2-9 microg/L, n = 16) and the high arsenic counties (>or=10 microg/L, n = 5) compared to the low arsenic counties (<2.0 microg/L, n = 23). When adjusted for race, gender, population density, smoking and body mass index (BMI), no relationship was found between arsenic levels in ground water and cancer incidence. CONCLUSIONS: In this ecological design, exposure to low-level arsenic in ground water is not associated with cancer incidence when adjusting for salient variables. For populations residing in southwestern Idaho, where arsenic has been found to exceed 10 microg/L in ground water, individual risk assessment is required in order to determine whether there is a link between long-term arsenic exposure at these levels and cancer risk."
376,Ahsan et al. 2003,Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase," Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. We examined whether genetic susceptibility, as determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively, are associated with the risk of arsenic-induced hyperkeratotic skin lesions-precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7-6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after adjustment for arsenic exposure and other covariates. Subjects carrying the high-risk MPO genotype and with high arsenic exposure were at almost six times (OR 5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Similarly, highly exposed subjects carrying the high-risk CAT genotype were at more than four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Our findings, although based on small numbers, suggest that the oxidative stress genes MPO and CAT may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions.","Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalaseAbs: Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. We examined whether genetic susceptibility, as determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively, are associated with the risk of arsenic-induced hyperkeratotic skin lesions-precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7-6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after adjustment for arsenic exposure and other covariates. Subjects carrying the high-risk MPO genotype and with high arsenic exposure were at almost six times (OR 5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Similarly, highly exposed subjects carrying the high-risk CAT genotype were at more than four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Our findings, although based on small numbers, suggest that the oxidative stress genes MPO and CAT may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions."
377,Liao et al. 2009,Risk assessment of arsenic-induced internal cancer at long-term low dose exposure," Previous epidemiological studies have indicated that ingested inorganic arsenic is strongly associated with a wide spectrum of internal cancers. Little is conducted, however, to assess health effects at long-term low dose exposures by linking biologically based mechanistic models and arsenic epidemiological data. We present an integrated approach by linking the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate reference arsenic guideline. The proposed epidemiological data are based on an 8 years follow-up study of 10,138 residents in arseniasis-endemic areas in southwestern and northeastern Taiwan. The 0.01% and 1% excess lifetime cancer risk based point-of-departure analysis were adopted to quantify the internal cancer risks from arsenic in drinking water. Positive relationships between arsenic exposures and cumulative incidence ratios of bladder, lung, and urinary-related cancers were found using Weibull dose-response model r(2)=0.58-0.89). The result shows that the reference arsenic guideline is recommended to be 3.4 microg L(-1) based on male bladder cancer with an excess risk of 10(-4) for a 75-year lifetime exposure. The likelihood of reference arsenic guideline and excess lifetime cancer risk estimates range from 1.9-10.2 microg L(-1) and 2.84 x 10(-5) to 1.96 x 10(-4), respectively, based on the drinking water uptake rates of 1.08-6.52 L d(-1). This study implicates that the Weibull model-based arsenic epidemiological and the PBPK framework can provide a scientific basis to quantify internal cancer risks from arsenic in drinking water and to further recommend the reference drinking water arsenic guideline.","Risk assessment of arsenic-induced internal cancer at long-term low dose exposureAbs: Previous epidemiological studies have indicated that ingested inorganic arsenic is strongly associated with a wide spectrum of internal cancers. Little is conducted, however, to assess health effects at long-term low dose exposures by linking biologically based mechanistic models and arsenic epidemiological data. We present an integrated approach by linking the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate reference arsenic guideline. The proposed epidemiological data are based on an 8 years follow-up study of 10,138 residents in arseniasis-endemic areas in southwestern and northeastern Taiwan. The 0.01% and 1% excess lifetime cancer risk based point-of-departure analysis were adopted to quantify the internal cancer risks from arsenic in drinking water. Positive relationships between arsenic exposures and cumulative incidence ratios of bladder, lung, and urinary-related cancers were found using Weibull dose-response model r(2)=0.58-0.89). The result shows that the reference arsenic guideline is recommended to be 3.4 microg L(-1) based on male bladder cancer with an excess risk of 10(-4) for a 75-year lifetime exposure. The likelihood of reference arsenic guideline and excess lifetime cancer risk estimates range from 1.9-10.2 microg L(-1) and 2.84 x 10(-5) to 1.96 x 10(-4), respectively, based on the drinking water uptake rates of 1.08-6.52 L d(-1). This study implicates that the Weibull model-based arsenic epidemiological and the PBPK framework can provide a scientific basis to quantify internal cancer risks from arsenic in drinking water and to further recommend the reference drinking water arsenic guideline."
378,Liao et al. 2008,A Weibull-PBPK model for assessing risk of arsenic-induced skin lesions in children," Chronic arsenic exposure and skin lesions (keratosis and hyperpigmentation) are inextricably linked. This paper was to quantify the children skin lesions risks and to further recommend safe drinking water arsenic standard based on reported arsenic epidemiological data. We linked the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate safe drinking water arsenic concentrations and to perform the risk characterization. We calculated odds ratios (ORs) to assess the relative magnitude of the effect of the arsenic exposure on the likelihood of the prevalence of children skin lesions by calculating proposed Weibull-based prevalence ratios of exposed to control groups associated with the age group-specific PBPK model predicted dimethylarsinite (MMA(III)) levels in urine. Positive relationships between arsenic exposures and cumulative prevalence ratios of skin lesions were found using Weibull dose-response model (r2=0.91-0.96). We reported that the safe drinking water arsenic standards were recommended to be 2.2 and 1 microg/L for male and 6 and 2.8 microg/L for female in 0-6 and 7-18 years age groups, respectively, based on hyperpigmentation with an excess risk of 10(-3) for a 75 years lifetime exposure. Risk predictions indicate that estimated ORs have 95% confidence intervals of 1.33-5.12, 1.74-19.15, and 2.81-19.27 based on mean drinking water arsenic contents of 283.19, 282.65, and 468.81 microg/L, respectively, in West Bengal, India, Bangladesh, and southwestern Taiwan. Our findings also suggest that increasing urinary monomethylarsonic acid (MMA) levels are associated with an increase in risks of arsenic-induced children skin lesions.","A Weibull-PBPK model for assessing risk of arsenic-induced skin lesions in childrenAbs: Chronic arsenic exposure and skin lesions (keratosis and hyperpigmentation) are inextricably linked. This paper was to quantify the children skin lesions risks and to further recommend safe drinking water arsenic standard based on reported arsenic epidemiological data. We linked the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate safe drinking water arsenic concentrations and to perform the risk characterization. We calculated odds ratios (ORs) to assess the relative magnitude of the effect of the arsenic exposure on the likelihood of the prevalence of children skin lesions by calculating proposed Weibull-based prevalence ratios of exposed to control groups associated with the age group-specific PBPK model predicted dimethylarsinite (MMA(III)) levels in urine. Positive relationships between arsenic exposures and cumulative prevalence ratios of skin lesions were found using Weibull dose-response model (r2=0.91-0.96). We reported that the safe drinking water arsenic standards were recommended to be 2.2 and 1 microg/L for male and 6 and 2.8 microg/L for female in 0-6 and 7-18 years age groups, respectively, based on hyperpigmentation with an excess risk of 10(-3) for a 75 years lifetime exposure. Risk predictions indicate that estimated ORs have 95% confidence intervals of 1.33-5.12, 1.74-19.15, and 2.81-19.27 based on mean drinking water arsenic contents of 283.19, 282.65, and 468.81 microg/L, respectively, in West Bengal, India, Bangladesh, and southwestern Taiwan. Our findings also suggest that increasing urinary monomethylarsonic acid (MMA) levels are associated with an increase in risks of arsenic-induced children skin lesions."
379,Haque et al. 2003,"Arsenic in drinking water and skin lesions: Dose-response data from West Bengal, India"," BACKGROUND: Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. METHODS: We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. RESULTS: The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. CONCLUSIONS: The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.","Arsenic in drinking water and skin lesions: Dose-response data from West Bengal, IndiaAbs: BACKGROUND: Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. METHODS: We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. RESULTS: The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. CONCLUSIONS: The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions."
380,Lin et al. 1998,"Arsenic species in drinking water, hair, fingernails, and urine of patients with blackfoot disease"," A large number of residents on the southwest coast of Taiwan suffer from an endemic peripheral vascular disease called blackfoot disease. Although the etiology has been investigated since 1958, the cause of blackfoot disease remains unknown. Certain substances contained in artesian well water have been implicated as causal factors, including arsenic as the predominant element. Data in this study demonstrated that in the well water collected from blackfoot disease regions of Taiwan there was a marked increase in total arsenic concentrations, with the predominant species being inorganic arsenical compounds. The concentrations of organic methyl arsenicals were present in minimal amounts. The excretion of total arsenic, inorganic arsenic, monomethylarsonic acid, and trimethylarsenic acid in the urine of patients afflicted with blackfoot disease was significantly higher than for control subjects. Further, in patients with blackfoot disease the concentrations of total arsenic and inorganic arsenic were markedly elevated in the hair and fingernails. Data suggest that blackfoot disease is associated with individuals ingesting well, water contaminated with arsenic primarily in the inorganic form and that hair, fingernails, or urine specimens serve as equally effective biomarkers of exposure. The fact that arsenic intoxication as manifested by blackfoot disease is still prevalent despite the stoppage of well-water consumption for two decades illustrates the persistent nature of arsenic action.","Arsenic species in drinking water, hair, fingernails, and urine of patients with blackfoot diseaseAbs: A large number of residents on the southwest coast of Taiwan suffer from an endemic peripheral vascular disease called blackfoot disease. Although the etiology has been investigated since 1958, the cause of blackfoot disease remains unknown. Certain substances contained in artesian well water have been implicated as causal factors, including arsenic as the predominant element. Data in this study demonstrated that in the well water collected from blackfoot disease regions of Taiwan there was a marked increase in total arsenic concentrations, with the predominant species being inorganic arsenical compounds. The concentrations of organic methyl arsenicals were present in minimal amounts. The excretion of total arsenic, inorganic arsenic, monomethylarsonic acid, and trimethylarsenic acid in the urine of patients afflicted with blackfoot disease was significantly higher than for control subjects. Further, in patients with blackfoot disease the concentrations of total arsenic and inorganic arsenic were markedly elevated in the hair and fingernails. Data suggest that blackfoot disease is associated with individuals ingesting well, water contaminated with arsenic primarily in the inorganic form and that hair, fingernails, or urine specimens serve as equally effective biomarkers of exposure. The fact that arsenic intoxication as manifested by blackfoot disease is still prevalent despite the stoppage of well-water consumption for two decades illustrates the persistent nature of arsenic action."
381,Ahsan et al. 2006,Health Effects of Arsenic Longitudinal Study (HEALS): Description of a multidisciplinary epidemiologic investigation," Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and children's cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 microg/l, 25-100 microg/l, and <25 microg/l. Average urinary As concentrations were 140 and 136 microg/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure.","Health Effects of Arsenic Longitudinal Study (HEALS): Description of a multidisciplinary epidemiologic investigationAbs: Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and children's cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 microg/l, 25-100 microg/l, and <25 microg/l. Average urinary As concentrations were 140 and 136 microg/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure."
382,Lin et al. 2008,Associations between arsenic in drinking water and pterygium in southwestern Taiwan," Pterygium is a fibrovascular growth of the bulbar conjunctiva and underlying subconjunctival tissue that may cause blindness. The mechanism of pterygium formation is not yet fully understood, but pterygium has some tumorlike features.<br /><br /> The objective of this study was to evaluate the association between arsenic exposure through drinking water and the occurrence of pterygium in southwestern Taiwan.<br /><br /> We recruited participants &gt; 40 years of age from three villages in the arseniasis-endemic area in southwestern Taiwan (exposure villages) and four neighboring nonendemic villages (comparison villages). Each participant received an eye examination and a questionnaire interview. Photographs taken of both eyes were later graded by an ophthalmologist to determine pterygium status.<br /><br /> We included 223 participants from the exposure villages and 160 from the comparison villages. The prevalence of pterygium was higher in the exposure villages across all age groups in both sexes and increased with cumulative arsenic exposure. We found a significant association between cumulative arsenic exposure and the prevalence of pterygium. After adjusting for age, sex, working under sunlight, and working in sandy environments, we found that cumulative arsenic exposure of 0.1-15.0 mg/L-year and &gt; or = 15.1 mg/L-year were associated with increased risks of developing pterygium. The adjusted odds ratios were 2.04 [95% confidence interval (CI), 1.04-3.99] and 2.88 (95% CI, 1.42-5.83), respectively.<br /><br /> Chronic exposure to arsenic in drinking water was related to the occurrence of pterygium, and the association was still observed after adjusting for exposures to sunlight and sandy environments.","Associations between arsenic in drinking water and pterygium in southwestern TaiwanAbs: Pterygium is a fibrovascular growth of the bulbar conjunctiva and underlying subconjunctival tissue that may cause blindness. The mechanism of pterygium formation is not yet fully understood, but pterygium has some tumorlike features.<br /><br /> The objective of this study was to evaluate the association between arsenic exposure through drinking water and the occurrence of pterygium in southwestern Taiwan.<br /><br /> We recruited participants &gt; 40 years of age from three villages in the arseniasis-endemic area in southwestern Taiwan (exposure villages) and four neighboring nonendemic villages (comparison villages). Each participant received an eye examination and a questionnaire interview. Photographs taken of both eyes were later graded by an ophthalmologist to determine pterygium status.<br /><br /> We included 223 participants from the exposure villages and 160 from the comparison villages. The prevalence of pterygium was higher in the exposure villages across all age groups in both sexes and increased with cumulative arsenic exposure. We found a significant association between cumulative arsenic exposure and the prevalence of pterygium. After adjusting for age, sex, working under sunlight, and working in sandy environments, we found that cumulative arsenic exposure of 0.1-15.0 mg/L-year and &gt; or = 15.1 mg/L-year were associated with increased risks of developing pterygium. The adjusted odds ratios were 2.04 [95% confidence interval (CI), 1.04-3.99] and 2.88 (95% CI, 1.42-5.83), respectively.<br /><br /> Chronic exposure to arsenic in drinking water was related to the occurrence of pterygium, and the association was still observed after adjusting for exposures to sunlight and sandy environments."
383,Ahsan et al. 2003,DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis," Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers.","DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosisAbs: Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers."
384,Lindberg et al. 2005,"Arsenic exposure in Hungary, Romania and Slovakia"," Inorganic arsenic is a potent human carcinogen and toxicant which people are exposed to mainly via drinking water and food. The objective of the present study was to assess current exposure to arsenic via drinking water in three European countries. For this purpose, 520 individuals from four Hungarian, two Slovakian and two Romanian countries were investigated by measuring inorganic arsenic and methylated arsenic metabolites in urine by high performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry. Arsenic in drinking water was determined by atomic absorption spectrometry. Significantly higher concentrations of arsenic were found in both the water and the urine samples from the Hungarian counties (median: 11 and 15 microg dm(-3), respectively; p &lt; 0.001) than from the Slovakian (median: 0.94 and 4.5 microg dm(-3), respectively) and Romanian (median: 0.70 and 2.1 microg dm(-3), respectively) counties. A significant correlation was seen between arsenic in water and arsenic in urine (R(2)= 0.46). At low water arsenic concentrations, the relative amount of dimethylarsinic acid (DMA) in urine was increased, indicating exposure via food. Also, high body mass index was associated with higher concentrations of arsenic in urine (p= 0.03), mostly in the form of DMA. Smokers had significantly higher urinary arsenic concentrations than non-smokers (p= 0.03). In conclusion, elevated arsenic exposure via drinking water was prevalent in some of the counties. Exposure to arsenic from food, mainly as DMA, and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water.","Arsenic exposure in Hungary, Romania and SlovakiaAbs: Inorganic arsenic is a potent human carcinogen and toxicant which people are exposed to mainly via drinking water and food. The objective of the present study was to assess current exposure to arsenic via drinking water in three European countries. For this purpose, 520 individuals from four Hungarian, two Slovakian and two Romanian countries were investigated by measuring inorganic arsenic and methylated arsenic metabolites in urine by high performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry. Arsenic in drinking water was determined by atomic absorption spectrometry. Significantly higher concentrations of arsenic were found in both the water and the urine samples from the Hungarian counties (median: 11 and 15 microg dm(-3), respectively; p &lt; 0.001) than from the Slovakian (median: 0.94 and 4.5 microg dm(-3), respectively) and Romanian (median: 0.70 and 2.1 microg dm(-3), respectively) counties. A significant correlation was seen between arsenic in water and arsenic in urine (R(2)= 0.46). At low water arsenic concentrations, the relative amount of dimethylarsinic acid (DMA) in urine was increased, indicating exposure via food. Also, high body mass index was associated with higher concentrations of arsenic in urine (p= 0.03), mostly in the form of DMA. Smokers had significantly higher urinary arsenic concentrations than non-smokers (p= 0.03). In conclusion, elevated arsenic exposure via drinking water was prevalent in some of the counties. Exposure to arsenic from food, mainly as DMA, and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water."
385,Lindberg et al. 2008,Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh," Although genetic polymorphisms have been shown to explain some of the large variation observed in the metabolism of inorganic arsenic there may be several other factors playing an important role, e.g. nutrition. The objective of this study was to elucidate the influence of various factors on current arsenic exposure and metabolism in Matlab, a rural area in Bangladesh, where elevated water arsenic concentrations and malnutrition are prevalent. In total 1571 individuals, randomly selected from all inhabitants above 5 years of age, were investigated by measuring arsenic in urine and drinking water. In a subset of 526 randomly selected individuals, arsenic metabolites were speciated using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). A significant association was observed between arsenic in urine and drinking water (R2 ¼ 0.41). The contribution to urinary arsenic from arsenic exposure from food and other water sources was calculated to be almost 50 mg/L. The individuals in the present study had remarkably efficient methylation, in spite of high exposure and prevalence of malnutrition. Gender and age were major factors influencing arsenic metabolism in this population with a median of 77 mg/L of arsenic in urine (range: 0.5–1994 mg/L). Women had higher arsenic methylation efficiency than men, but only in childbearing age, supporting an influence of sex hormones. Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic.","Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in BangladeshAbs: Although genetic polymorphisms have been shown to explain some of the large variation observed in the metabolism of inorganic arsenic there may be several other factors playing an important role, e.g. nutrition. The objective of this study was to elucidate the influence of various factors on current arsenic exposure and metabolism in Matlab, a rural area in Bangladesh, where elevated water arsenic concentrations and malnutrition are prevalent. In total 1571 individuals, randomly selected from all inhabitants above 5 years of age, were investigated by measuring arsenic in urine and drinking water. In a subset of 526 randomly selected individuals, arsenic metabolites were speciated using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). A significant association was observed between arsenic in urine and drinking water (R2 ¼ 0.41). The contribution to urinary arsenic from arsenic exposure from food and other water sources was calculated to be almost 50 mg/L. The individuals in the present study had remarkably efficient methylation, in spite of high exposure and prevalence of malnutrition. Gender and age were major factors influencing arsenic metabolism in this population with a median of 77 mg/L of arsenic in urine (range: 0.5–1994 mg/L). Women had higher arsenic methylation efficiency than men, but only in childbearing age, supporting an influence of sex hormones. Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic."
386,Lindberg et al. 2008,The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure," It is known that a high fraction of methylarsonate (MA) in urine is a risk modifying factor for several arsenic induced health effects, including skin lesions, and that men are more susceptible for developing skin lesions than women. Thus, we aimed at elucidating the interaction between gender and arsenic metabolism for the risk of developing skin lesions. This study is part of a population-based case-referent study concerning the risk for skin lesions in relation to arsenic exposure via drinking water carried out in Matlab, a rural area 53km south-east of Dhaka, Bangladesh. We randomly selected 526 from 1579 referents and all 504 cases for analysis of arsenic metabolites in urine using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). The present study confirm previous studies, with the risk for skin lesions being almost three times higher in the highest tertile of %MA (adjusted OR 2.8, 95% CI: 1.9–4.2, p b 0.001) compared to the lowest tertile. The present study is the first to show that the well documented higher risk for men to develop arsenic-related skin lesions compared to women is mainly explained by the less efficient methylation of arsenic, as defined by a higher fraction of MA and lower fraction of DMA in the urine, among men. Our previously documented lower risk for skin lesions in individuals exposed since infancy, or before, was found to be independent of the observed arsenic methylation efficiency. Thus, it can be speculated that this is due to a programming effect of arsenic in utero.","The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposureAbs: It is known that a high fraction of methylarsonate (MA) in urine is a risk modifying factor for several arsenic induced health effects, including skin lesions, and that men are more susceptible for developing skin lesions than women. Thus, we aimed at elucidating the interaction between gender and arsenic metabolism for the risk of developing skin lesions. This study is part of a population-based case-referent study concerning the risk for skin lesions in relation to arsenic exposure via drinking water carried out in Matlab, a rural area 53km south-east of Dhaka, Bangladesh. We randomly selected 526 from 1579 referents and all 504 cases for analysis of arsenic metabolites in urine using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). The present study confirm previous studies, with the risk for skin lesions being almost three times higher in the highest tertile of %MA (adjusted OR 2.8, 95% CI: 1.9–4.2, p b 0.001) compared to the lowest tertile. The present study is the first to show that the well documented higher risk for men to develop arsenic-related skin lesions compared to women is mainly explained by the less efficient methylation of arsenic, as defined by a higher fraction of MA and lower fraction of DMA in the urine, among men. Our previously documented lower risk for skin lesions in individuals exposed since infancy, or before, was found to be independent of the observed arsenic methylation efficiency. Thus, it can be speculated that this is due to a programming effect of arsenic in utero."
387,Ahsan et al. 2006,Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: Baseline results from the Health Effects of Arsenic Longitudinal Study," Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.","Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: Baseline results from the Health Effects of Arsenic Longitudinal StudyAbs: Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions."
388,He et al. 2007,Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion," Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.","Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortionAbs: Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency."
389,Ahsan et al. 2000,Associations between drinking water and urinary arsenic levels and skin lesions in Bangladesh," The present study examined the associations between drinking water and urinary arsenic levels and skin lesions among 167 residents of three contiguous villages in Bangladesh. Thirty-six (21.6%) had skin lesions (melanosis, hyperkeratosis, or both), of which 13 (36.1%) occurred in subjects who were currently drinking water containing concentrations of arsenic < 50 micrograms/L. The risk for skin lesions in relation to the exposure estimates based on urinary arsenic was elevated more than 3-fold, with the odds ratios for the highest versus the lowest quartiles being 3.6 (95% confidence interval, 1.2 to 12.1) for urinary total arsenic and 3.2 (95% confidence interval, 1.1 to 10.0) for urinary creatinine-adjusted total arsenic. The risks for skin lesions in relation to the exposure estimates based on arsenic in drinking water were less strongly elevated, with the odds ratios for the highest versus the lowest quartiles of exposure being 1.7 (95% confidence interval, 0.6 to 5.1) for drinking-water arsenic and 2.3 for cumulative arsenic index. The study suggests that arsenic exposure is associated with skin lesions in the Bangladesh population and that urinary arsenic may be a stronger predictor of skin lesions than arsenic in drinking water in this population.","Associations between drinking water and urinary arsenic levels and skin lesions in BangladeshAbs: The present study examined the associations between drinking water and urinary arsenic levels and skin lesions among 167 residents of three contiguous villages in Bangladesh. Thirty-six (21.6%) had skin lesions (melanosis, hyperkeratosis, or both), of which 13 (36.1%) occurred in subjects who were currently drinking water containing concentrations of arsenic < 50 micrograms/L. The risk for skin lesions in relation to the exposure estimates based on urinary arsenic was elevated more than 3-fold, with the odds ratios for the highest versus the lowest quartiles being 3.6 (95% confidence interval, 1.2 to 12.1) for urinary total arsenic and 3.2 (95% confidence interval, 1.1 to 10.0) for urinary creatinine-adjusted total arsenic. The risks for skin lesions in relation to the exposure estimates based on arsenic in drinking water were less strongly elevated, with the odds ratios for the highest versus the lowest quartiles of exposure being 1.7 (95% confidence interval, 0.6 to 5.1) for drinking-water arsenic and 2.3 for cumulative arsenic index. The study suggests that arsenic exposure is associated with skin lesions in the Bangladesh population and that urinary arsenic may be a stronger predictor of skin lesions than arsenic in drinking water in this population."
390,Heck et al. 2007,Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh," BACKGROUND: Inorganic arsenic (InAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and this methylation facilitates urinary arsenic excretion. Previous studies suggest that persons with more complete methylation, characterized as greater proportions of DMA and lesser proportions of MMA and InAs in urine, have a lower risk of adverse arsenic-related health outcomes. OBJECTIVE: The purpose of this study was to examine whether the capacity to methylate arsenic differs by nutrient intake. DESIGN: Participants were 1016 Bangladeshi adults exposed to arsenic in drinking water. Nutrient intake was assessed with a validated food-frequency questionnaire. Multivariate regression analyses were used to examine associations of nutrients with urinary arsenic metabolite profiles. RESULTS: In multivariate analyses, higher intakes of cysteine, methionine, calcium, protein, and vitamin B-12 were associated with lower percentages of InAs and higher ratios of MMA to InAs in urine. Higher intakes of niacin (beta=0.22, P=0.02) and choline (beta=0.10, P=0.02) were associated with higher DMA-to-MMA ratios, after adjustment for age, sex, smoking, total urinary arsenic, and total energy intake. CONCLUSIONS: Findings from the current study show the influence of multiple nutrients on arsenic methylation. In particular, this study highlights the potential importance of dietary intakes of cysteine, methionine, niacin, vitamin B-12, and choline on health effects of arsenic by modulating its metabolism.","Consumption of folate-related nutrients and metabolism of arsenic in BangladeshAbs: BACKGROUND: Inorganic arsenic (InAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and this methylation facilitates urinary arsenic excretion. Previous studies suggest that persons with more complete methylation, characterized as greater proportions of DMA and lesser proportions of MMA and InAs in urine, have a lower risk of adverse arsenic-related health outcomes. OBJECTIVE: The purpose of this study was to examine whether the capacity to methylate arsenic differs by nutrient intake. DESIGN: Participants were 1016 Bangladeshi adults exposed to arsenic in drinking water. Nutrient intake was assessed with a validated food-frequency questionnaire. Multivariate regression analyses were used to examine associations of nutrients with urinary arsenic metabolite profiles. RESULTS: In multivariate analyses, higher intakes of cysteine, methionine, calcium, protein, and vitamin B-12 were associated with lower percentages of InAs and higher ratios of MMA to InAs in urine. Higher intakes of niacin (beta=0.22, P=0.02) and choline (beta=0.10, P=0.02) were associated with higher DMA-to-MMA ratios, after adjustment for age, sex, smoking, total urinary arsenic, and total energy intake. CONCLUSIONS: Findings from the current study show the influence of multiple nutrients on arsenic methylation. In particular, this study highlights the potential importance of dietary intakes of cysteine, methionine, niacin, vitamin B-12, and choline on health effects of arsenic by modulating its metabolism."
391,Heck et al. 2009,Lung cancer in a U.S. population with low to moderate arsenic exposure," BACKGROUND: Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water. OBJECTIVES: We examined associations between arsenic and lung cancer. METHODS: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level). RESULTS: Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease. CONCLUSION: Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.","Lung cancer in a U.S. population with low to moderate arsenic exposureAbs: BACKGROUND: Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water. OBJECTIVES: We examined associations between arsenic and lung cancer. METHODS: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level). RESULTS: Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease. CONCLUSION: Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies."
392,Heck et al. 2008,Arsenic exposure and anemia in Bangladesh: A population-based study," OBJECTIVE: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration. METHODS: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately. RESULTS: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin. CONCLUSIONS: The study suggests an association between high arsenic exposure and anemia in Bangladesh.","Arsenic exposure and anemia in Bangladesh: A population-based studyAbs: OBJECTIVE: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration. METHODS: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately. RESULTS: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin. CONCLUSIONS: The study suggests an association between high arsenic exposure and anemia in Bangladesh."
393,Hinwood et al. 1999,Cancer incidence and high environmental arsenic concentrations in rural populations: Results of an ecological study," Geographical areas of rural Victoria, Australia, with surface soil inorganic arsenic concentrations of >100 mg/kg and/or drinking water arsenic concentrations >0.01 mg/litre were selected and the relationship with cancer incidence was investigated. Standardized incidence rates (SIRs) for cancer were generated for 22 areas during 1982-91 using Victorian Cancer Registry data and Victorian cancer rates as a baseline. SIRs were also generated for combined areas according to environmental exposure type (whether an area had high soil and/or high water arsenic concentrations). The SIRs for both males and females for the combined 22 areas were increased for all cancers 1.06 (95% confidence interval, CI; 1.03-1.09), prostate cancer 1.14 (1.05-1.23), kidney cancer 1.16 (0.98-1.37), melanoma 1.36 (1.24-1.48), chronic myeloid leukaemia 1.54 (1.13-2.10) and breast cancer in females 1.10 (1.03-1.18). When stratifying into exposure categories, the SIR for prostate cancer was significant at 1.20 (1.06-1.36) for the high soil/high water category only. No significant dose-response relationship between drinking water and individual cancers was observed. It is concluded that of the cancers associated with environmental arsenic exposure, only prostate cancer incidence was significantly elevated in this study. This result was likely confounded by a number of factors and was limited by low power and exposure misclassification.","Cancer incidence and high environmental arsenic concentrations in rural populations: Results of an ecological studyAbs: Geographical areas of rural Victoria, Australia, with surface soil inorganic arsenic concentrations of >100 mg/kg and/or drinking water arsenic concentrations >0.01 mg/litre were selected and the relationship with cancer incidence was investigated. Standardized incidence rates (SIRs) for cancer were generated for 22 areas during 1982-91 using Victorian Cancer Registry data and Victorian cancer rates as a baseline. SIRs were also generated for combined areas according to environmental exposure type (whether an area had high soil and/or high water arsenic concentrations). The SIRs for both males and females for the combined 22 areas were increased for all cancers 1.06 (95% confidence interval, CI; 1.03-1.09), prostate cancer 1.14 (1.05-1.23), kidney cancer 1.16 (0.98-1.37), melanoma 1.36 (1.24-1.48), chronic myeloid leukaemia 1.54 (1.13-2.10) and breast cancer in females 1.10 (1.03-1.18). When stratifying into exposure categories, the SIR for prostate cancer was significant at 1.20 (1.06-1.36) for the high soil/high water category only. No significant dose-response relationship between drinking water and individual cancers was observed. It is concluded that of the cancers associated with environmental arsenic exposure, only prostate cancer incidence was significantly elevated in this study. This result was likely confounded by a number of factors and was limited by low power and exposure misclassification."
394,Andrew et al. 2006,Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic," The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown ; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action.","Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenicAbs: The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown ; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action."
395,Hopenhayn et al. 2003,Arsenic exposure from drinking water and birth weight," BACKGROUND: Arsenic exposures from drinking water increase the risk of various cancers and noncancer health endpoints. Limited evidence suggests that arsenic may have adverse human reproductive effects. We investigated the association between drinking water arsenic exposure and fetal growth, as manifest in birth weight. METHODS: We conducted a prospective cohort study in two Chilean cities with contrasting drinking water arsenic levels: Antofagasta (40 micro g/L) and Valparaíso (<1 micro g/L). Study subjects completed in-depth interviews and provided urine samples for exposure analysis. We obtained pregnancy and birth information from medical records. The birth weight analysis was restricted to liveborn, singleton infants born between December 1998 and February 2000. RESULTS: The final study group consisted of 424 infants from Antofagasta and 420 from Valparaíso. After controlling for confounders, results of the multivariable analysis indicated that Antofagasta infants had lower mean birth weight (-57 g; 95% confidence interval = -123 to 9). CONCLUSION: This study suggests that moderate arsenic exposures from drinking water (<50 micro g/L) during pregnancy are associated with reduction in birth weight, similar in magnitude to that resulting from other environmental exposures such as environmental tobacco smoke and benzene.","Arsenic exposure from drinking water and birth weightAbs: BACKGROUND: Arsenic exposures from drinking water increase the risk of various cancers and noncancer health endpoints. Limited evidence suggests that arsenic may have adverse human reproductive effects. We investigated the association between drinking water arsenic exposure and fetal growth, as manifest in birth weight. METHODS: We conducted a prospective cohort study in two Chilean cities with contrasting drinking water arsenic levels: Antofagasta (40 micro g/L) and Valparaíso (<1 micro g/L). Study subjects completed in-depth interviews and provided urine samples for exposure analysis. We obtained pregnancy and birth information from medical records. The birth weight analysis was restricted to liveborn, singleton infants born between December 1998 and February 2000. RESULTS: The final study group consisted of 424 infants from Antofagasta and 420 from Valparaíso. After controlling for confounders, results of the multivariable analysis indicated that Antofagasta infants had lower mean birth weight (-57 g; 95% confidence interval = -123 to 9). CONCLUSION: This study suggests that moderate arsenic exposures from drinking water (<50 micro g/L) during pregnancy are associated with reduction in birth weight, similar in magnitude to that resulting from other environmental exposures such as environmental tobacco smoke and benzene."
396,Hopenhayn et al. 2006,Association between arsenic exposure from drinking water and anemia during pregnancy," OBJECTIVE: Arsenic is associated with numerous health effects. We investigated the association between arsenic exposure from drinking water and anemia during pregnancy. METHODS: We conducted a prospective cohort pregnancy study in two Chilean cities with contrasting drinking water arsenic levels: 40 microg/L versus <1 microg/L. This analysis included 810 women who gave birth to live, singleton infants and had at least one hemoglobin determination during pregnancy. RESULTS: Arsenic exposed women were more likely to be anemic during pregnancy after adjusting for other factors. Furthermore, as pregnancy progressed, the prevalence of anemia rose more sharply among those in the exposed versus unexposed city: 49% versus 17%. CONCLUSION: This study suggests an association between moderate arsenic in drinking water and anemia during pregnancy. Further research is needed to identify the specific types of anemia underlying the association.","Association between arsenic exposure from drinking water and anemia during pregnancyAbs: OBJECTIVE: Arsenic is associated with numerous health effects. We investigated the association between arsenic exposure from drinking water and anemia during pregnancy. METHODS: We conducted a prospective cohort pregnancy study in two Chilean cities with contrasting drinking water arsenic levels: 40 microg/L versus <1 microg/L. This analysis included 810 women who gave birth to live, singleton infants and had at least one hemoglobin determination during pregnancy. RESULTS: Arsenic exposed women were more likely to be anemic during pregnancy after adjusting for other factors. Furthermore, as pregnancy progressed, the prevalence of anemia rose more sharply among those in the exposed versus unexposed city: 49% versus 17%. CONCLUSION: This study suggests an association between moderate arsenic in drinking water and anemia during pregnancy. Further research is needed to identify the specific types of anemia underlying the association."
397,Hopenhayn et al. 2003,Profile of urinary arsenic metabolites during pregnancy," Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.","Profile of urinary arsenic metabolites during pregnancyAbs: Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic."
398,Hopenhayn-Rich et al. 2000,Chronic arsenic exposure and risk of infant mortality in two areas of Chile," Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used a retrospective study design to examine time and location patterns in infant mortality between 1950 and 1996, using univariate statistics, graphical techniques, and Poisson regression analysis. Results of the study document the general declines in late fetal and infant mortality over the study period in both locations. The data also indicate an elevation of the late fetal, neonatal, and postneonatal mortality rates for Antofagasta, relative to Valparaíso, for specific time periods, which generally coincide with the period of highest arsenic concentration in the drinking water of Antofagasta. Poisson regression analysis yielded an elevated and significant association between arsenic exposure and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI), 1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The findings from this investigation may support a role for arsenic exposure in increasing the risk of late fetal and infant mortality.","Chronic arsenic exposure and risk of infant mortality in two areas of ChileAbs: Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used a retrospective study design to examine time and location patterns in infant mortality between 1950 and 1996, using univariate statistics, graphical techniques, and Poisson regression analysis. Results of the study document the general declines in late fetal and infant mortality over the study period in both locations. The data also indicate an elevation of the late fetal, neonatal, and postneonatal mortality rates for Antofagasta, relative to Valparaíso, for specific time periods, which generally coincide with the period of highest arsenic concentration in the drinking water of Antofagasta. Poisson regression analysis yielded an elevated and significant association between arsenic exposure and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI), 1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The findings from this investigation may support a role for arsenic exposure in increasing the risk of late fetal and infant mortality."
399,Andrew et al. 2003,Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water," Arsenic is well established as a human carcinogen, but its precise mechanism of action remains unknown. Arsenic does not directly damage DNA, but may act as a carcinogen through inhibition of DNA repair mechanisms, leading indirectly to increased mutations from other DNA damaging agents. The molecular mechanism underlying arsenic inhibition of nucleotide excision repair after UV irradiation (Hartwig et al., Carcinogenesis 1997;18:399-405) is unknown, but could be due to decreased expression of critical genes involved in nucleotide excision repair of damaged DNA. This hypothesis was tested by analyzing expression of repair genes and arsenic exposure in a subset of 16 individuals enrolled in a population based case-control study investigating arsenic exposure and cancer risk in New Hampshire. Toenail arsenic levels were inversely correlated with expression of critical members of the nucleotide excision repair complex, ERCC1 (r(2) = 0.82, p < 0.0001), XPF (r(2) = 0.56, p < 0.002), and XPB (r(2) = 0.75, p < 0.0001). The internal dose marker, toenail arsenic level, was more strongly associated with changes in expression of these genes than drinking water arsenic concentration. Our findings, based on human exposure to arsenic in a US population, show an association between biomarkers of arsenic exposure and expression of DNA repair genes. Although our findings need verification in a larger study group, they are consistent with the hypothesis that inhibition of DNA repair capacity is a potential mechanism for the co-carcinogenic activity of arsenic. Copyright 2003 Wiley-Liss, Inc.","Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking waterAbs: Arsenic is well established as a human carcinogen, but its precise mechanism of action remains unknown. Arsenic does not directly damage DNA, but may act as a carcinogen through inhibition of DNA repair mechanisms, leading indirectly to increased mutations from other DNA damaging agents. The molecular mechanism underlying arsenic inhibition of nucleotide excision repair after UV irradiation (Hartwig et al., Carcinogenesis 1997;18:399-405) is unknown, but could be due to decreased expression of critical genes involved in nucleotide excision repair of damaged DNA. This hypothesis was tested by analyzing expression of repair genes and arsenic exposure in a subset of 16 individuals enrolled in a population based case-control study investigating arsenic exposure and cancer risk in New Hampshire. Toenail arsenic levels were inversely correlated with expression of critical members of the nucleotide excision repair complex, ERCC1 (r(2) = 0.82, p < 0.0001), XPF (r(2) = 0.56, p < 0.002), and XPB (r(2) = 0.75, p < 0.0001). The internal dose marker, toenail arsenic level, was more strongly associated with changes in expression of these genes than drinking water arsenic concentration. Our findings, based on human exposure to arsenic in a US population, show an association between biomarkers of arsenic exposure and expression of DNA repair genes. Although our findings need verification in a larger study group, they are consistent with the hypothesis that inhibition of DNA repair capacity is a potential mechanism for the co-carcinogenic activity of arsenic. Copyright 2003 Wiley-Liss, Inc."
400,Lu et al. 2004,Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood," Four trivalent arsenic species, inorganic arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), and phenylarsine oxide (PhAs(III)O), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the alpha and beta chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAs(III), MMA(III), and DMA(III) showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the alpha chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.","Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat bloodAbs: Four trivalent arsenic species, inorganic arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), and phenylarsine oxide (PhAs(III)O), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the alpha and beta chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAs(III), MMA(III), and DMA(III) showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the alpha chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins."
401,Hopenhayn-Rich et al. 1998,"Lung and kidney cancer mortality associated with arsenic in drinking water in Cardoba, Argentina"," BACKGROUND: Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Córdoba, Argentina, which has a well-documented history of arsenic exposure from drinking water. METHODS: Mortality from lung, kidney, liver and skin cancers during the period 1986-1991 in Córdoba's 26 counties was investigated, expanding the authors' previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population. RESULTS: We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group. CONCLUSIONS: The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear.","Lung and kidney cancer mortality associated with arsenic in drinking water in Cardoba, ArgentinaAbs: BACKGROUND: Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Córdoba, Argentina, which has a well-documented history of arsenic exposure from drinking water. METHODS: Mortality from lung, kidney, liver and skin cancers during the period 1986-1991 in Córdoba's 26 counties was investigated, expanding the authors' previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population. RESULTS: We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group. CONCLUSIONS: The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear."
402,Andrewes et al. 2003,Dimethylarsine and trimethylarsine are potent genotoxins in vitro," The mechanism of arsenic carcinogenesis is unclear. A complicating factor receiving increasing attention is that arsenic is biomethylated to form various metabolites. Eleven different arsenicals were studied for in vitro genotoxicity to supercoiled DNA (pBR 322 and phiX174). Five arsenicals showed various degrees of positivity-monomethylarsonous acid, dimethylarsinous acid, monomethylarsine, dimethylarsine, and trimethylarsine. Supercoiled DNA, blotted on nitrocellulose filter paper, was exposed to gaseous arsines by suspending the filter paper above aqueous reaction mixtures of sodium borohydride and an appropriate arsenical. All three methylated arsines damaged DNA; inorganic arsine did not. Arsines were generated in situ in reaction mixtures containing DNA by reaction of sodium borohydride with arsenite, monomethylarsonous acid, dimethylarsinous acid, and trimethylarsine oxide, at pH 8.0. Both dimethylarsine and trimethylarsine (generated from 200 micro M dimethylarsinous acid and trimethylarsine oxide, respectively) damaged DNA in less than 30 min. Under certain conditions, the two most potent genotoxic arsines, trimethylarsine and dimethylarsine, are about 100 times more potent than dimethylarsinous acid (the most potent genotoxic arsenical previously known). There was no evidence to suggest that anything other than the arsines caused the DNA damage. Possible models for the biological production of arsines were examined. The coenzymes, NADH and NADPH, are biological hydride donors. When NADH or NADPH (5 mM) were incubated with dimethylarsinous acid (0-2 mM) for 2 h, DNA damage was increased by at least 10-fold. A possible explanation for this result is that these compounds react with dimethylarsinous acid to generate dimethylarsine. DNA was incubated with a dithiol compound, dithioerythritol (5 mM), and trimethylarsine oxide (0.5 mM) for 2 h, and the reduction of trimethylarsine oxide to trimethylarsine resulted in DNA damage.","Dimethylarsine and trimethylarsine are potent genotoxins in vitroAbs: The mechanism of arsenic carcinogenesis is unclear. A complicating factor receiving increasing attention is that arsenic is biomethylated to form various metabolites. Eleven different arsenicals were studied for in vitro genotoxicity to supercoiled DNA (pBR 322 and phiX174). Five arsenicals showed various degrees of positivity-monomethylarsonous acid, dimethylarsinous acid, monomethylarsine, dimethylarsine, and trimethylarsine. Supercoiled DNA, blotted on nitrocellulose filter paper, was exposed to gaseous arsines by suspending the filter paper above aqueous reaction mixtures of sodium borohydride and an appropriate arsenical. All three methylated arsines damaged DNA; inorganic arsine did not. Arsines were generated in situ in reaction mixtures containing DNA by reaction of sodium borohydride with arsenite, monomethylarsonous acid, dimethylarsinous acid, and trimethylarsine oxide, at pH 8.0. Both dimethylarsine and trimethylarsine (generated from 200 micro M dimethylarsinous acid and trimethylarsine oxide, respectively) damaged DNA in less than 30 min. Under certain conditions, the two most potent genotoxic arsines, trimethylarsine and dimethylarsine, are about 100 times more potent than dimethylarsinous acid (the most potent genotoxic arsenical previously known). There was no evidence to suggest that anything other than the arsines caused the DNA damage. Possible models for the biological production of arsines were examined. The coenzymes, NADH and NADPH, are biological hydride donors. When NADH or NADPH (5 mM) were incubated with dimethylarsinous acid (0-2 mM) for 2 h, DNA damage was increased by at least 10-fold. A possible explanation for this result is that these compounds react with dimethylarsinous acid to generate dimethylarsine. DNA was incubated with a dithiol compound, dithioerythritol (5 mM), and trimethylarsine oxide (0.5 mM) for 2 h, and the reduction of trimethylarsine oxide to trimethylarsine resulted in DNA damage."
403,Hore et al. 2007,Detecting arsenic-related skin lesions: Experiences from a large community-based survey in Bangladesh," A cross-sectional survey was conducted in Matlab, Bangladesh, to determine the prevalence of skin lesions (a three-step procedure) associated with arsenic exposure and discuss validity and feasibility in relation to recommended screening algorithms. Cases with skin lesions were identified by screening above 4 years of age (n = 166,934). Trained field teams conducted a careful house-to-house screening and identified 1682 individuals with skin lesions, who were referred to physicians for confirmation. Physicians diagnosed 579 cases as probable and documented all these with digital photographs. Two experts inspected all photographs for consensus agreement that was reached for 504 cases. Using the experts' opinions as reference, the positive predictive value of the physicians' diagnosis was 87% (male = 82% vs. female = 94%; p < 0.01). The physicians had difficulties in separating arsenic-induced keratosis from differential diagnoses, while probability for correct diagnosis was high for arsenic-related pigmentation changes. Including information on current arsenic concentration in drinking water (which was masked at time of skin examination) or urine in the diagnostic algorithm should have increased the number of false negative cases. In the present transition of drinking water sources these markers of current exposure levels provide no information on past exposure. A 2-3 step procedure with house-to-house screening and clinic-based confirmation of arsenic-induced skin lesions is a feasible approach. Information on arsenic concentration in current water sources or in urine should not have improved the precision in the diagnosis. These results may have policy implications for community screening of arsenic-related skin lesions in Bangladesh and elsewhere.","Detecting arsenic-related skin lesions: Experiences from a large community-based survey in BangladeshAbs: A cross-sectional survey was conducted in Matlab, Bangladesh, to determine the prevalence of skin lesions (a three-step procedure) associated with arsenic exposure and discuss validity and feasibility in relation to recommended screening algorithms. Cases with skin lesions were identified by screening above 4 years of age (n = 166,934). Trained field teams conducted a careful house-to-house screening and identified 1682 individuals with skin lesions, who were referred to physicians for confirmation. Physicians diagnosed 579 cases as probable and documented all these with digital photographs. Two experts inspected all photographs for consensus agreement that was reached for 504 cases. Using the experts' opinions as reference, the positive predictive value of the physicians' diagnosis was 87% (male = 82% vs. female = 94%; p < 0.01). The physicians had difficulties in separating arsenic-induced keratosis from differential diagnoses, while probability for correct diagnosis was high for arsenic-related pigmentation changes. Including information on current arsenic concentration in drinking water (which was masked at time of skin examination) or urine in the diagnostic algorithm should have increased the number of false negative cases. In the present transition of drinking water sources these markers of current exposure levels provide no information on past exposure. A 2-3 step procedure with house-to-house screening and clinic-based confirmation of arsenic-induced skin lesions is a feasible approach. Information on arsenic concentration in current water sources or in urine should not have improved the precision in the diagnosis. These results may have policy implications for community screening of arsenic-related skin lesions in Bangladesh and elsewhere."
404,Hou et al. 2005,Effects of glutamine on adhesion molecule expression and leukocyte transmigration in endothelial cells exposed to arsenic," This study evaluated whether glutamine (GLN) concentration was related to endothelial surface molecule expression and the migration of polymorphonuclear neutrophils (PMNs) through endothelial cells (ECs) stimulated by arsenic. Human umbilical vein endothelial cells (HUVECs) and PMNs were treated with different GLN concentrations (0, 300, 600 and 1000 microM) for 24 h. After that, we stimulated HUVECs for 3 h with 0.5 microM arsenic, and PMNs were allowed to transmigrate to ECs for 2 h. HUVEC surface expressions of cell adhesion molecules and integrin (CD11b) and interleukin (IL)-8 receptor expressions on PMNs were measured. The transendothelial migration of PMNs was also analyzed. The results showed that cell adhesion molecule (CAM) and integrin expressions in arsenic groups were higher than in those without arsenic. Among the arsenic groups, the expression of CAMs on ECs and CD11b, and IL-8 receptor on PMNs was lowest with 0 microM compared with the other GLN concentrations. Vascular CAM-1 on ECs and CD11b on PMN expression were higher with 300 microM than with 600 and 1000 microM GLN. IL-8 secretions from ECs and PMNs were higher with 300 muM than with 600 and 1000 microM GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. Polymorphonuclear neutrophil transmigration was significantly higher with 300 muM GLN than with other GLN concentrations. These results suggest that ECs and PMNs were activated after arsenic stimulation. Cell adhesion molecule expressions on ECs and PMNs were suppressed in the absence of GLN. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. Glutamine administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression; PMN transmigration was also decreased after stimulation with arsenic.","Effects of glutamine on adhesion molecule expression and leukocyte transmigration in endothelial cells exposed to arsenicAbs: This study evaluated whether glutamine (GLN) concentration was related to endothelial surface molecule expression and the migration of polymorphonuclear neutrophils (PMNs) through endothelial cells (ECs) stimulated by arsenic. Human umbilical vein endothelial cells (HUVECs) and PMNs were treated with different GLN concentrations (0, 300, 600 and 1000 microM) for 24 h. After that, we stimulated HUVECs for 3 h with 0.5 microM arsenic, and PMNs were allowed to transmigrate to ECs for 2 h. HUVEC surface expressions of cell adhesion molecules and integrin (CD11b) and interleukin (IL)-8 receptor expressions on PMNs were measured. The transendothelial migration of PMNs was also analyzed. The results showed that cell adhesion molecule (CAM) and integrin expressions in arsenic groups were higher than in those without arsenic. Among the arsenic groups, the expression of CAMs on ECs and CD11b, and IL-8 receptor on PMNs was lowest with 0 microM compared with the other GLN concentrations. Vascular CAM-1 on ECs and CD11b on PMN expression were higher with 300 microM than with 600 and 1000 microM GLN. IL-8 secretions from ECs and PMNs were higher with 300 muM than with 600 and 1000 microM GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. Polymorphonuclear neutrophil transmigration was significantly higher with 300 muM GLN than with other GLN concentrations. These results suggest that ECs and PMNs were activated after arsenic stimulation. Cell adhesion molecule expressions on ECs and PMNs were suppressed in the absence of GLN. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. Glutamine administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression; PMN transmigration was also decreased after stimulation with arsenic."
405,Hour et al. 2006,Differential expression of molecular markers in arsenic- and non-arsenic-related urothelial cancer," BACKGROUND: Little is known about the mechanisms of arsenic-related urothelial cancer (AsUC). The aim of this study was to reveal the differential expression of molecular markers between AsUC and non-arsenic-related UC (non-AsUC). MATERIALS AND METHODS: Tissues of AsUC (n=33), non-AsUC (n=20) and normal bladder urothelia from patients with benign diseases (n=4) were examined for multiple selected molecular markers responsible for various cellular functions, includingglutathione, GST-pi, Bcl-2, p53 and c-Fos. RESULTS: The mean cellular glutathione content of normal mucosal samples (33.4 +/- 7.2 microM/mg protein) was significantly higher than either non-AsUC (22.8 +/- 1.8, p = 0.04) or AsUC (16.4 +/- 1.6, p = 0.002). The glutathione content of non-AsUC was higher than that of AsUC (p = 0.012). The expressions of Bcl-2 and c-Fos in AsUC were significantly higher than those in non-AsUC (p = 0.004 and p = 0.02, respectively). CONCLUSION: The carcinogenic pathway for AsUC is different, in part, from that of non-AsUC. Cellular glutathione contents may be down-regulated during urothelial carcinogenesis. Bcl-2 and c-Fos may play important roles in arsenic-mediated carcinogenesis of the urothelium.","Differential expression of molecular markers in arsenic- and non-arsenic-related urothelial cancerAbs: BACKGROUND: Little is known about the mechanisms of arsenic-related urothelial cancer (AsUC). The aim of this study was to reveal the differential expression of molecular markers between AsUC and non-arsenic-related UC (non-AsUC). MATERIALS AND METHODS: Tissues of AsUC (n=33), non-AsUC (n=20) and normal bladder urothelia from patients with benign diseases (n=4) were examined for multiple selected molecular markers responsible for various cellular functions, includingglutathione, GST-pi, Bcl-2, p53 and c-Fos. RESULTS: The mean cellular glutathione content of normal mucosal samples (33.4 +/- 7.2 microM/mg protein) was significantly higher than either non-AsUC (22.8 +/- 1.8, p = 0.04) or AsUC (16.4 +/- 1.6, p = 0.002). The glutathione content of non-AsUC was higher than that of AsUC (p = 0.012). The expressions of Bcl-2 and c-Fos in AsUC were significantly higher than those in non-AsUC (p = 0.004 and p = 0.02, respectively). CONCLUSION: The carcinogenic pathway for AsUC is different, in part, from that of non-AsUC. Cellular glutathione contents may be down-regulated during urothelial carcinogenesis. Bcl-2 and c-Fos may play important roles in arsenic-mediated carcinogenesis of the urothelium."
406,Hsieh et al. 2008,Risk of erectile dysfunction induced by arsenic exposure through well water consumption in Taiwan," BACKGROUND: Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. OBJECTIVES: In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. METHODS: We recruited 177 males >or= 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone-binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). RESULTS: The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non-arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure <or= 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. CONCLUSIONS: Results suggested that chronic arsenic exposure has a negative impact on erectile function.","Risk of erectile dysfunction induced by arsenic exposure through well water consumption in TaiwanAbs: BACKGROUND: Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. OBJECTIVES: In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. METHODS: We recruited 177 males >or= 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone-binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). RESULTS: The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non-arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure <or= 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. CONCLUSIONS: Results suggested that chronic arsenic exposure has a negative impact on erectile function."
407,Applebaum et al. 2007,"Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New Hampshire"," BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.","Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New HampshireAbs: BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic."
408,Hsieh et al. 2008,Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan," Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) >or=1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with epsilon4 allele of APOE than those without epsilon4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level >10 microg/L or had arsenic exposure >0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1.","Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in TaiwanAbs: Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) >or=1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with epsilon4 allele of APOE than those without epsilon4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level >10 microg/L or had arsenic exposure >0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1."
409,Argos et al. 2007,Socioeconomic status and risk for arsenic-related skin lesions in Bangladesh," OBJECTIVES: Arsenic contamination of groundwater is a severe public health crisis in Bangladesh, where the population is exposed to arsenic in drinking water through tube wells used for groundwater collection. In this study, we explored the association between socioeconomic status and arsenic toxicity. METHODS: We used baseline data from 11438 men and women who were recruited into the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study on the health effects of arsenic exposure in Bangladesh. We conducted analyses with logistic regression and generalized estimating equations. RESULTS: We found a strong dose-response association with all measures of arsenic exposure and skin lesions. We also found that the effect of arsenic was modified by land ownership on a multiplicative scale, with an increased risk among non-land owners associated with well water arsenic (P=.04) and urinary total arsenic concentrations (P=.03). CONCLUSIONS: Our study provides insight into potentially modifiable host characteristics and identifies factors that may effectively target susceptible population subgroups for appropriate interventions.","Socioeconomic status and risk for arsenic-related skin lesions in BangladeshAbs: OBJECTIVES: Arsenic contamination of groundwater is a severe public health crisis in Bangladesh, where the population is exposed to arsenic in drinking water through tube wells used for groundwater collection. In this study, we explored the association between socioeconomic status and arsenic toxicity. METHODS: We used baseline data from 11438 men and women who were recruited into the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study on the health effects of arsenic exposure in Bangladesh. We conducted analyses with logistic regression and generalized estimating equations. RESULTS: We found a strong dose-response association with all measures of arsenic exposure and skin lesions. We also found that the effect of arsenic was modified by land ownership on a multiplicative scale, with an increased risk among non-land owners associated with well water arsenic (P=.04) and urinary total arsenic concentrations (P=.03). CONCLUSIONS: Our study provides insight into potentially modifiable host characteristics and identifies factors that may effectively target susceptible population subgroups for appropriate interventions."
410,Hsu et al. 2006,Plasma-transforming growth factor-alpha expression in residents of an arseniasis area in Taiwan," Epidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5+/-38.2 pg ml-1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1+/-5.6 pg ml-1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population.","Plasma-transforming growth factor-alpha expression in residents of an arseniasis area in TaiwanAbs: Epidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5+/-38.2 pg ml-1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1+/-5.6 pg ml-1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population."
411,Hsueh et al. 2005,Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension," The association of 4 genetic polymorphisms, NAD(P)H oxidase, manganesesuperoxide dismutase (MnSOD), catalase, and endothelial nitric oxide synthase (e-NOS), was assessed with arsenic-related hypertension risk among 79 hypertensive cases and 213 controls in an arseniasis-hyperendemic area of Taiwan. Overall, MnSOD polymorphism significantly increased the risk of hypertension regardless of arsenic exposure. NADPH oxidase and eNOS polymorphisms were significantly associated with hypertension risk in the high arsenic exposure group; however, catalase polymorphism was not associated with hypertension. Groups were further stratified by triglyceride levels to evaluate whether the cumulative arsenic exposure combined the three polymorphisms together. The adjusted adds ratios (ORs) of at least two risk factors of the cumulative arsenic exposure and MnSOD, NADPH oxidase, and eNOS three-polymorphism combination versus any one risk factor of them were 0.8 (95% CI 0.3-2.3) for individuals with low triglyceride levels (<110 mg/dl) and 2.5 (95% CI 1.0-6.01) for high-triglyceride groups (>110 mg/dl), respectively. These results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels.","Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertensionAbs: The association of 4 genetic polymorphisms, NAD(P)H oxidase, manganesesuperoxide dismutase (MnSOD), catalase, and endothelial nitric oxide synthase (e-NOS), was assessed with arsenic-related hypertension risk among 79 hypertensive cases and 213 controls in an arseniasis-hyperendemic area of Taiwan. Overall, MnSOD polymorphism significantly increased the risk of hypertension regardless of arsenic exposure. NADPH oxidase and eNOS polymorphisms were significantly associated with hypertension risk in the high arsenic exposure group; however, catalase polymorphism was not associated with hypertension. Groups were further stratified by triglyceride levels to evaluate whether the cumulative arsenic exposure combined the three polymorphisms together. The adjusted adds ratios (ORs) of at least two risk factors of the cumulative arsenic exposure and MnSOD, NADPH oxidase, and eNOS three-polymorphism combination versus any one risk factor of them were 0.8 (95% CI 0.3-2.3) for individuals with low triglyceride levels (<110 mg/dl) and 2.5 (95% CI 1.0-6.01) for high-triglyceride groups (>110 mg/dl), respectively. These results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels."
412,Hu et al. 2006,"Effects of arsenic exposure among semiconductor workers: A cautionary note on urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine"," Arsenic is a notorious environmental toxicant and was found to cause oxidative stress in cultured cells and animals. However, little work has been done in human studies, especially for the population occupationally exposed to arsenic. In order to investigate the effect of occupational exposure to arsenic in oxidative stress, we measured urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) from 90 semiconductor workers including 50 exposed and 40 nonexposed subjects. A highly sensitive and specific isotope dilution LC-MS/MS method was used for quantification of 8-oxodGuo. The levels of inorganic arsenic (iAs3+, iAs5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine were determined by high-performance liquid chromatography-flow injection atomic absorption spectrometry (HPLC-FIAAS). Results showed that the mean urinary concentrations of total arsenic and 8-oxodGuo were significantly higher for exposed workers compared with the nonexposed workers. In addition, elevated urinary 8-oxodGuo concentrations of exposed workers were correlated with urinary levels of MMA (r = 0.44, P < 0.005) and the extent of primary methylation (the ratio of MMA to inorganic arsenic) (r = 0.40, P < 0.005). These findings suggested that occupational exposure to arsenic could result in the induction of oxidative stress. The presence and/or formation of MMA could play an important role in arsenic-involved injuries.","Effects of arsenic exposure among semiconductor workers: A cautionary note on urinary 8-oxo-7,8-dihydro-2'-deoxyguanosineAbs: Arsenic is a notorious environmental toxicant and was found to cause oxidative stress in cultured cells and animals. However, little work has been done in human studies, especially for the population occupationally exposed to arsenic. In order to investigate the effect of occupational exposure to arsenic in oxidative stress, we measured urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) from 90 semiconductor workers including 50 exposed and 40 nonexposed subjects. A highly sensitive and specific isotope dilution LC-MS/MS method was used for quantification of 8-oxodGuo. The levels of inorganic arsenic (iAs3+, iAs5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine were determined by high-performance liquid chromatography-flow injection atomic absorption spectrometry (HPLC-FIAAS). Results showed that the mean urinary concentrations of total arsenic and 8-oxodGuo were significantly higher for exposed workers compared with the nonexposed workers. In addition, elevated urinary 8-oxodGuo concentrations of exposed workers were correlated with urinary levels of MMA (r = 0.44, P < 0.005) and the extent of primary methylation (the ratio of MMA to inorganic arsenic) (r = 0.40, P < 0.005). These findings suggested that occupational exposure to arsenic could result in the induction of oxidative stress. The presence and/or formation of MMA could play an important role in arsenic-involved injuries."
413,Huang et al. 2007,Arsenic methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern Taiwan," BACKGROUND: Cumulative arsenic exposure (CAE) from drinking water has been shown to be associated with hypertension in a dose-response pattern. This study further explored the association between arsenic methylation capability and hypertension risk among residents of arseniasis-hyperendemic areas in Taiwan considering the effect of CAE and other potential confounders. METHOD: There were 871 subjects (488 women and 383 men) and among them 372 were diagnosed as having hypertension based on a positive history or measured systolic blood pressure >or=140 mm Hg and/or diastolic blood pressure >or=90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generator and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA(V)) divided by (As(III)+As(V))] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA(V)) were used as indicators for arsenic methylation capability. RESULTS: The level of urinary arsenic was still significantly correlated with cumulative arsenic exposure (CAE) calculated from a questionnaire interview (p=0.02) even after the residents stopped drinking the artesian well water for 2-3 decades. Hypertensive subjects had higher percentages of MMA(V) and lower SMI than subjects without hypertension. However, subjects having CAE >0 mg/L-year had higher hypertension risk than those who had CAE=0 mg/L-year disregard a high or low methylation index. CONCLUSION: Inefficient arsenic methylation ability may be related with hypertension risk.","Arsenic methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern TaiwanAbs: BACKGROUND: Cumulative arsenic exposure (CAE) from drinking water has been shown to be associated with hypertension in a dose-response pattern. This study further explored the association between arsenic methylation capability and hypertension risk among residents of arseniasis-hyperendemic areas in Taiwan considering the effect of CAE and other potential confounders. METHOD: There were 871 subjects (488 women and 383 men) and among them 372 were diagnosed as having hypertension based on a positive history or measured systolic blood pressure >or=140 mm Hg and/or diastolic blood pressure >or=90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generator and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA(V)) divided by (As(III)+As(V))] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA(V)) were used as indicators for arsenic methylation capability. RESULTS: The level of urinary arsenic was still significantly correlated with cumulative arsenic exposure (CAE) calculated from a questionnaire interview (p=0.02) even after the residents stopped drinking the artesian well water for 2-3 decades. Hypertensive subjects had higher percentages of MMA(V) and lower SMI than subjects without hypertension. However, subjects having CAE >0 mg/L-year had higher hypertension risk than those who had CAE=0 mg/L-year disregard a high or low methylation index. CONCLUSION: Inefficient arsenic methylation ability may be related with hypertension risk."
414,Arkusz et al. 2005,Modulation of murine peritoneal macrophage function by chronic exposure to arsenate in drinking water," Exposure of humans to arsenic is associated with various adverse health effects including immunotoxicity and elevated risk of cancer development. Specific mechanisms of these effects are not well understood. In the present study we investigated some functional parameters of peritoneal macrophages isolated from mice exposed for 12 weeks to sodium arsenate in drinking water at 0.5, 5, and 50 mgAs/l. The experimental conditions were matched with the environmental conditions of arsenic exposure in humans. To characterize function of the macrophages, we assessed their ability to release nitric oxide (NO), reactive oxygen species (ROS), and tumor necrosis factor-alpha (TNF-alpha) in response to common stimulants. To this end the isolated cells were stimulated with lipopolysaccharide (1 microg/ml) to assess NO and TNF-alpha production (the WEHI-164 bioassay) or with phorbol myristate acetate (5 microg/ml) to assess superoxide production (NBT reduction test). As a result, in mice exposed to 0.5, 5, and 50 mgAs/l we observed decreased production of NO (9 +/- 2, 8 +/- 2, 11 +/- 5 microM NO2-, respectively, versus 27 +/- 7 microM in control) and superoxide (41.3 +/- 18.2%, 52.8 +/- 15.1% and 55.9 +/- 12.9%, respectively, less than in control). Despite reduced NO production, expression of iNOS mRNA in RT-PCR, showed similar levels in exposed and control animals. We did not see any significant influence of the exposure on TNF-alpha release and mRNA expression. The potential consequences of decreased production of NO and superoxide by peritoneal macrophages as observed in exposed mice may suggest impaired response of the cells against infection or developing tumor cells.","Modulation of murine peritoneal macrophage function by chronic exposure to arsenate in drinking waterAbs: Exposure of humans to arsenic is associated with various adverse health effects including immunotoxicity and elevated risk of cancer development. Specific mechanisms of these effects are not well understood. In the present study we investigated some functional parameters of peritoneal macrophages isolated from mice exposed for 12 weeks to sodium arsenate in drinking water at 0.5, 5, and 50 mgAs/l. The experimental conditions were matched with the environmental conditions of arsenic exposure in humans. To characterize function of the macrophages, we assessed their ability to release nitric oxide (NO), reactive oxygen species (ROS), and tumor necrosis factor-alpha (TNF-alpha) in response to common stimulants. To this end the isolated cells were stimulated with lipopolysaccharide (1 microg/ml) to assess NO and TNF-alpha production (the WEHI-164 bioassay) or with phorbol myristate acetate (5 microg/ml) to assess superoxide production (NBT reduction test). As a result, in mice exposed to 0.5, 5, and 50 mgAs/l we observed decreased production of NO (9 +/- 2, 8 +/- 2, 11 +/- 5 microM NO2-, respectively, versus 27 +/- 7 microM in control) and superoxide (41.3 +/- 18.2%, 52.8 +/- 15.1% and 55.9 +/- 12.9%, respectively, less than in control). Despite reduced NO production, expression of iNOS mRNA in RT-PCR, showed similar levels in exposed and control animals. We did not see any significant influence of the exposure on TNF-alpha release and mRNA expression. The potential consequences of decreased production of NO and superoxide by peritoneal macrophages as observed in exposed mice may suggest impaired response of the cells against infection or developing tumor cells."
415,Arteel et al. 2008,Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice," Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases.","Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in miceAbs: Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases."
416,Avani and Rao 2007,Genotoxic effects in human lymphocytes exposed to arsenic and vitamin A," Arsenic is a ubiquitous trace element and a well-established human carcinogen. In search for an 'antidote' to this global poison, this work was undertaken to study the probable beneficial effect of vitamin A upon arsenic induced genotoxicity. Peripheral blood lymphocyte culture was carried out to study the effects of arsenic at three different dose levels (0.5, 1 and 2 microg) for 24 h prior to harvesting. In addition, mutagenic in vitro effect of ethyl methanesulphonate was studied as a positive control. Genotoxic variables presented here are sister chromatid exchanges (SCE), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT) and population doubling time (PDT). Inevitably, arsenic treatment showed dose-dependent augmentation in the incidences of SCE and CCPI/RI together with AGT and PDT. However, vitamin A supplemented arsenic cultures demonstrated remarkable resurgence in the described genotoxic parameters. This data shows that vitamin A might be a useful interventional treatment in arsenic poisoning.","Genotoxic effects in human lymphocytes exposed to arsenic and vitamin AAbs: Arsenic is a ubiquitous trace element and a well-established human carcinogen. In search for an 'antidote' to this global poison, this work was undertaken to study the probable beneficial effect of vitamin A upon arsenic induced genotoxicity. Peripheral blood lymphocyte culture was carried out to study the effects of arsenic at three different dose levels (0.5, 1 and 2 microg) for 24 h prior to harvesting. In addition, mutagenic in vitro effect of ethyl methanesulphonate was studied as a positive control. Genotoxic variables presented here are sister chromatid exchanges (SCE), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT) and population doubling time (PDT). Inevitably, arsenic treatment showed dose-dependent augmentation in the incidences of SCE and CCPI/RI together with AGT and PDT. However, vitamin A supplemented arsenic cultures demonstrated remarkable resurgence in the described genotoxic parameters. This data shows that vitamin A might be a useful interventional treatment in arsenic poisoning."
417,Ayotte et al. 2006,Bladder cancer mortality and private well use in New England: An ecological study," STUDY OBJECTIVE: To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. DESIGN: Ecological study relating age adjusted cancer mortality rates for white men and women during 1985-1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. SETTING: The 504 state economic areas of the contiguous United States. PARTICIPANTS: Mortality analysis of 11 cancer sites, with the focus on bladder cancer. MAIN RESULTS: After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62). CONCLUSIONS: Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England.","Bladder cancer mortality and private well use in New England: An ecological studyAbs: STUDY OBJECTIVE: To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. DESIGN: Ecological study relating age adjusted cancer mortality rates for white men and women during 1985-1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. SETTING: The 504 state economic areas of the contiguous United States. PARTICIPANTS: Mortality analysis of 11 cancer sites, with the focus on bladder cancer. MAIN RESULTS: After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62). CONCLUSIONS: Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England."
418,Baastrup et al. 2008,Arsenic in drinking-water and risk for cancer in Denmark," BACKGROUND: Arsenic is a well-known carcinogen, which is often found in drinking-water. Epidemiologic studies have shown increased cancer risks among individuals exposed to high concentrations of arsenic in drinking-water, whereas studies of the carcinogenic effect of low doses have had inconsistent results. OBJECTIVE: Our aim was to determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer. METHODS: The study was based on a prospective Danish cohort of 57,053 persons in the Copenhagen and Aarhus areas. Cancer cases were identified in the Danish Cancer Registry, and the Danish civil registration system was used to trace and geocode residential addresses of the cohort members. We used a geographic information system to link addresses with water supply areas, then estimated individual exposure to arsenic using residential addresses back to 1970. Average exposure for the cohort ranged between 0.05 and 25.3 microg/L (mean = 1.2 microg/L). Cox's regression models were used to analyze possible relationships between arsenic and cancer. RESULTS: We found no significant association between exposure to arsenic and risk for cancers of the lung, bladder, liver, kidney, prostate, or colorectum, or melanoma skin cancer; however, the risk for non-melanoma skin cancer decreased with increasing exposure (incidence rate ratio = 0.88/microg/L average exposure; 95% confidence interval, 0.84-0.94). Results adjusted for enrollment area showed no association with non-melanoma skin cancer. CONCLUSIONS: The results indicate that exposure to low doses of arsenic might be associated with a reduced risk for skin cancer.","Arsenic in drinking-water and risk for cancer in DenmarkAbs: BACKGROUND: Arsenic is a well-known carcinogen, which is often found in drinking-water. Epidemiologic studies have shown increased cancer risks among individuals exposed to high concentrations of arsenic in drinking-water, whereas studies of the carcinogenic effect of low doses have had inconsistent results. OBJECTIVE: Our aim was to determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer. METHODS: The study was based on a prospective Danish cohort of 57,053 persons in the Copenhagen and Aarhus areas. Cancer cases were identified in the Danish Cancer Registry, and the Danish civil registration system was used to trace and geocode residential addresses of the cohort members. We used a geographic information system to link addresses with water supply areas, then estimated individual exposure to arsenic using residential addresses back to 1970. Average exposure for the cohort ranged between 0.05 and 25.3 microg/L (mean = 1.2 microg/L). Cox's regression models were used to analyze possible relationships between arsenic and cancer. RESULTS: We found no significant association between exposure to arsenic and risk for cancers of the lung, bladder, liver, kidney, prostate, or colorectum, or melanoma skin cancer; however, the risk for non-melanoma skin cancer decreased with increasing exposure (incidence rate ratio = 0.88/microg/L average exposure; 95% confidence interval, 0.84-0.94). Results adjusted for enrollment area showed no association with non-melanoma skin cancer. CONCLUSIONS: The results indicate that exposure to low doses of arsenic might be associated with a reduced risk for skin cancer."
419,Babu et al. 2006,Interactive alterations of arsenic and malathion in the disposition kinetics of pefloxacin," Assessment of deleterious effects produced by concurrent exposure to commonly encountered chemicals is of great concern to find out toxicological consequences arising as a result of their interactions and for a more comprehensive management of chemical-induced untoward effects. The naturally occurring heavy metal arsenic is present in food and water. Malathion is one of the most widely used pesticides in agriculture and public health practices worldwide. Humans, animals, and birds are exposed to these chemicals through environmental processes. Since arsenic and malathion are shown to exert an inhibitory effect on cytochrome P450 activities, their continuous exposure may alter the disposition kinetics of drugs that are predominantly metabolized hepatically. The current study was undertaken to evaluate the impact of subchronic exposure of arsenic, malathion, and their combination on the disposition kinetics of widely used fluoroquinolone antimicrobial pefloxacin in chickens. Broiler chickens were exposed to either arsenic (50 ppm), malathion (500 ppm), or arsenic (50 ppm) plus malathion (500 ppm). Arsenic and malathion were given in drinking water and feed, respectively. Following 28 days of exposure, all birds received a single oral dose of pefloxacin (10 mg/kg) and the plasma concentrations and the disposition kinetic parameters of the drug were determined. In the birds not exposed to arsenic and/or malathion, the elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (C(max)), mean residence time (MRT), and bioavailability of pefloxacin were 8.46 +/- 0.24 h, 39.06 +/- 1.13 microg.h.ml(-1), 2.69 +/- 0.19 microg.ml(-1), 12.29 +/- 0.48 h, and 60.52 +/- 1.74%, respectively. Exposure to arsenic was associated with a significant increase in C(max) (4.28 +/- 0.45 microg.ml(-1)) and a nonsignificant increase in the values of AUC (48.96 +/- 2.55 microg.h.ml(-1)) and bioavailability (74.55 +/- 3.8 %) of pefloxacin. The values of AUC (51.62 +/- 4.76 microg.h.ml(-1)), t(1/2beta) (12.57 +/- 1.26 h), MRT (19.94 +/- 1.99 h), and bioavailability (78.59 +/- 7.25 %) of pefloxacin were significantly increased in malathion-exposed birds. Concomitant exposure to arsenic and malathion did not affect the disposition kinetic variables of pefloxacin. The study shows that subchronic malathion exposure significantly alters the elimination kinetics of pefloxacin. Following concurrent exposure, arsenic nullifies the malathion-induced changes in disposition kinetics of pefloxacin by possibly diminishing the cytochrome P450-catalyzed bioactivation of malathion.","Interactive alterations of arsenic and malathion in the disposition kinetics of pefloxacinAbs: Assessment of deleterious effects produced by concurrent exposure to commonly encountered chemicals is of great concern to find out toxicological consequences arising as a result of their interactions and for a more comprehensive management of chemical-induced untoward effects. The naturally occurring heavy metal arsenic is present in food and water. Malathion is one of the most widely used pesticides in agriculture and public health practices worldwide. Humans, animals, and birds are exposed to these chemicals through environmental processes. Since arsenic and malathion are shown to exert an inhibitory effect on cytochrome P450 activities, their continuous exposure may alter the disposition kinetics of drugs that are predominantly metabolized hepatically. The current study was undertaken to evaluate the impact of subchronic exposure of arsenic, malathion, and their combination on the disposition kinetics of widely used fluoroquinolone antimicrobial pefloxacin in chickens. Broiler chickens were exposed to either arsenic (50 ppm), malathion (500 ppm), or arsenic (50 ppm) plus malathion (500 ppm). Arsenic and malathion were given in drinking water and feed, respectively. Following 28 days of exposure, all birds received a single oral dose of pefloxacin (10 mg/kg) and the plasma concentrations and the disposition kinetic parameters of the drug were determined. In the birds not exposed to arsenic and/or malathion, the elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (C(max)), mean residence time (MRT), and bioavailability of pefloxacin were 8.46 +/- 0.24 h, 39.06 +/- 1.13 microg.h.ml(-1), 2.69 +/- 0.19 microg.ml(-1), 12.29 +/- 0.48 h, and 60.52 +/- 1.74%, respectively. Exposure to arsenic was associated with a significant increase in C(max) (4.28 +/- 0.45 microg.ml(-1)) and a nonsignificant increase in the values of AUC (48.96 +/- 2.55 microg.h.ml(-1)) and bioavailability (74.55 +/- 3.8 %) of pefloxacin. The values of AUC (51.62 +/- 4.76 microg.h.ml(-1)), t(1/2beta) (12.57 +/- 1.26 h), MRT (19.94 +/- 1.99 h), and bioavailability (78.59 +/- 7.25 %) of pefloxacin were significantly increased in malathion-exposed birds. Concomitant exposure to arsenic and malathion did not affect the disposition kinetic variables of pefloxacin. The study shows that subchronic malathion exposure significantly alters the elimination kinetics of pefloxacin. Following concurrent exposure, arsenic nullifies the malathion-induced changes in disposition kinetics of pefloxacin by possibly diminishing the cytochrome P450-catalyzed bioactivation of malathion."
420,Baker et al. 2005,Persistent neuropathy and hyperkeratosis from distant arsenic exposure,"<div>&nbsp;The purpose of this case series is to assess long-term sequelae of arsenic exposure in a cohort acutely exposed to arsenic in drinking water from a well dug into a landfill containing arsenical pesticides. Ten of the 13 individuals (or next of kin) in the initial study agreed to participate in the follow-up study. Next of kin provided questionnaire data and released medical information on the three individuals who had died. The remaining seven cohort members were assessed by an interview, questionnaire, detailed physical examination and sensory nerve testing. Available medical records were obtained and reviewed. Sensory testing was performed using an automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) evaluation. Sensory complaints and electrodiagnostic findings consistent with cy were found in a minority (3/7) of subjects 28 years after an acute toxic arsenic exposure. Two of the seven patients examined (1 of 3 with neuropathic findings) also had hyperkeratotic lesions consistent with arsenic toxicity and one of the patients had hyperpigmentation on their lower extremities possibly consistent with arsenic toxicity.</div>","Persistent neuropathy and hyperkeratosis from distant arsenic exposureAbs:<div>&nbsp;The purpose of this case series is to assess long-term sequelae of arsenic exposure in a cohort acutely exposed to arsenic in drinking water from a well dug into a landfill containing arsenical pesticides. Ten of the 13 individuals (or next of kin) in the initial study agreed to participate in the follow-up study. Next of kin provided questionnaire data and released medical information on the three individuals who had died. The remaining seven cohort members were assessed by an interview, questionnaire, detailed physical examination and sensory nerve testing. Available medical records were obtained and reviewed. Sensory testing was performed using an automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) evaluation. Sensory complaints and electrodiagnostic findings consistent with cy were found in a minority (3/7) of subjects 28 years after an acute toxic arsenic exposure. Two of the seven patients examined (1 of 3 with neuropathic findings) also had hyperkeratotic lesions consistent with arsenic toxicity and one of the patients had hyperpigmentation on their lower extremities possibly consistent with arsenic toxicity.</div>"
421,Banerjee et al. 2007,Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations," In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype.","Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrationsAbs: In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype."
422,Banerjee et al. 2008,Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals," In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p<0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis.","Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individualsAbs: In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p<0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis."
423,Milton and Rahman 2002,Respiratory effects and arsenic contaminated well water in Bangladesh," Arsenic in drinking water causes a widespread concern in Bangladesh, where a major proportion of tube wells is contaminated. Arsenic ingestion causes skin lesions, which is considered as definite exposure. A prevalence comparison study of respiratory effects among subjects with and without arsenic exposure through drinking water was conducted in Bangladesh. Exposed participants were recruited through health awareness campaign programs. Unexposed participants were randomly selected, where tubewells were not contaminated with arsenic. A total of 169 individuals participated (44 exposed individuals exhibiting skin lesions; 125 unexposed individuals). The arsenic concentrations ranged from 136 to 1000 micro g l(-1). The information regarding respiratory system signs and symptoms were also collected and the analyses were confined to nonsmokers. The crude prevalence ratio for chronic bronchitis and chronic cough amounted to 2.1 (95% CI 0.7-6.1). The prevalence ratios for chronic bronchitis increased with increasing exposure, i.e., 1.0, 1.6, 2.7 and 2.6 using unexposed as the reference. The prevalence ratios for chronic cough were 1.0, 1.6, 2.7 and 2.6 for the exposure categories, using the same unexposed as the reference. The dose-response trend was the same (P < 0.1) for both conditions. These results add to evidence that long-term ingestion of arsenic exposure can cause respiratory effects.","Respiratory effects and arsenic contaminated well water in BangladeshAbs: Arsenic in drinking water causes a widespread concern in Bangladesh, where a major proportion of tube wells is contaminated. Arsenic ingestion causes skin lesions, which is considered as definite exposure. A prevalence comparison study of respiratory effects among subjects with and without arsenic exposure through drinking water was conducted in Bangladesh. Exposed participants were recruited through health awareness campaign programs. Unexposed participants were randomly selected, where tubewells were not contaminated with arsenic. A total of 169 individuals participated (44 exposed individuals exhibiting skin lesions; 125 unexposed individuals). The arsenic concentrations ranged from 136 to 1000 micro g l(-1). The information regarding respiratory system signs and symptoms were also collected and the analyses were confined to nonsmokers. The crude prevalence ratio for chronic bronchitis and chronic cough amounted to 2.1 (95% CI 0.7-6.1). The prevalence ratios for chronic bronchitis increased with increasing exposure, i.e., 1.0, 1.6, 2.7 and 2.6 using unexposed as the reference. The prevalence ratios for chronic cough were 1.0, 1.6, 2.7 and 2.6 for the exposure categories, using the same unexposed as the reference. The dose-response trend was the same (P < 0.1) for both conditions. These results add to evidence that long-term ingestion of arsenic exposure can cause respiratory effects."
424,Bashir et al. 2006,Arsenic induced apoptosis in rat liver following repeated 60 days exposure," BACKGROUND: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 microM) concentration. AIM: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. METHODS: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. RESULTS: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. CONCLUSION: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis.","Arsenic induced apoptosis in rat liver following repeated 60 days exposureAbs: BACKGROUND: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 microM) concentration. AIM: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. METHODS: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. RESULTS: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. CONCLUSION: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis."
425,Basu et al. 2005,"Assessment of DNA damage in peripheral blood lymphocytes of individuals susceptible to arsenic induced toxicity in West Bengal, India"," Assessment of DNA damage was carried out using alkaline comet assay in lymphocytes of 30 individuals exposed to high levels of arsenic (247.12+/-18.93 microg/l) through contaminated groundwater in North 24 Parganas district, West Bengal, India. All of them exhibited high arsenic contents in nail (4.20+/-0.67 microg/g), hair (2.06+/-0.20 microg/g) and urine (259.75+/-33.89 microg/l) samples and manifested various arsenical skin lesions. Unexposed samples were collected from 30 residents of the unaffected East Midnapur district with very little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking water. The results were evaluated principally by manual analysis of comets and partly by computerized image analysis. Both the analytical methods exhibited a high degree of agreement in results. The exposed participants expressed significantly higher DNA damage (p < 0.01) in their lymphocytes than the unexposed participants. Alkaline comet assay was also combined with formamidopyrimidine-DNA glycosylase enzyme digestion to confirm that arsenic induced oxidative base damage in the lymphocytes. Significant positive trend effects of comet lengths in relation to arsenic levels in water prove that DNA damage can be used as a sensitive biomarker of arsenic exposure. This study demonstrates that arsenic induced significant DNA damage in the exposed participants, which could correspond to a higher susceptibility to arsenic induced toxicity and carcinogenicity.","Assessment of DNA damage in peripheral blood lymphocytes of individuals susceptible to arsenic induced toxicity in West Bengal, IndiaAbs: Assessment of DNA damage was carried out using alkaline comet assay in lymphocytes of 30 individuals exposed to high levels of arsenic (247.12+/-18.93 microg/l) through contaminated groundwater in North 24 Parganas district, West Bengal, India. All of them exhibited high arsenic contents in nail (4.20+/-0.67 microg/g), hair (2.06+/-0.20 microg/g) and urine (259.75+/-33.89 microg/l) samples and manifested various arsenical skin lesions. Unexposed samples were collected from 30 residents of the unaffected East Midnapur district with very little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking water. The results were evaluated principally by manual analysis of comets and partly by computerized image analysis. Both the analytical methods exhibited a high degree of agreement in results. The exposed participants expressed significantly higher DNA damage (p < 0.01) in their lymphocytes than the unexposed participants. Alkaline comet assay was also combined with formamidopyrimidine-DNA glycosylase enzyme digestion to confirm that arsenic induced oxidative base damage in the lymphocytes. Significant positive trend effects of comet lengths in relation to arsenic levels in water prove that DNA damage can be used as a sensitive biomarker of arsenic exposure. This study demonstrates that arsenic induced significant DNA damage in the exposed participants, which could correspond to a higher susceptibility to arsenic induced toxicity and carcinogenicity."
426,Milton et al. 2003,Non-cancer effects of chronic arsenicosis in Bangladesh: Preliminary results," A total of 136 patients were studied in three Upazillas of Laxmipur, Barisal and Madaripur districts were selected for health awareness campaign program. According to the existing data, these villages were ranked as high exposure. Demographic data of the patients investigated are showing pigmentation was seen in all—136 cases, keratosis was found only in 110 cases, and skin ulcer was detected in 13 cases. The predominant features are indicating respiratory sign and symptoms followed by conjunctival congestion and redness of eyes. Weakness was predominant symptom, and all most all cases reported weakness. There were few smokers (n = 16) and analyses were confined to non-smokers (n = 94). A total of the 94 subjects participated in this study. The sex ratio was 1:1.3 (male vs. female). The relative risk of chronic cough increased with age (RR = 2.12, for 26-50 age group; RR = 2.30 for age group more than 51) reflecting chronic exposure, but the 95% confidence intervals included unity. The relative risk of chronic bronchitis increased with age (RR = 2.68, for 26-50 age group; RR = 2.30 for age group more than 51) reflecting chronic exposure, but the 95% confidence intervals also included unity. The findings presented here provide evidence that ingestion of inorganic arsenic in drinking water may results in increases risk of chronic cough and bronchitis.","Non-cancer effects of chronic arsenicosis in Bangladesh: Preliminary resultsAbs: A total of 136 patients were studied in three Upazillas of Laxmipur, Barisal and Madaripur districts were selected for health awareness campaign program. According to the existing data, these villages were ranked as high exposure. Demographic data of the patients investigated are showing pigmentation was seen in all—136 cases, keratosis was found only in 110 cases, and skin ulcer was detected in 13 cases. The predominant features are indicating respiratory sign and symptoms followed by conjunctival congestion and redness of eyes. Weakness was predominant symptom, and all most all cases reported weakness. There were few smokers (n = 16) and analyses were confined to non-smokers (n = 94). A total of the 94 subjects participated in this study. The sex ratio was 1:1.3 (male vs. female). The relative risk of chronic cough increased with age (RR = 2.12, for 26-50 age group; RR = 2.30 for age group more than 51) reflecting chronic exposure, but the 95% confidence intervals included unity. The relative risk of chronic bronchitis increased with age (RR = 2.68, for 26-50 age group; RR = 2.30 for age group more than 51) reflecting chronic exposure, but the 95% confidence intervals also included unity. The findings presented here provide evidence that ingestion of inorganic arsenic in drinking water may results in increases risk of chronic cough and bronchitis."
427,Bates et al. 1995,Case-control study of bladder cancer and arsenic in drinking water," Mortality from several cancers, including bladder cancer, is elevated in a Taiwanese population exposed to high levels of arsenic in drinking water. Data from the Utah respondents to the National Bladder Cancer Study conducted in 1978 were used to evaluate these associations in a US population exposed to measurable, but much lower, levels of drinking water arsenic. Two indices of cumulative arsenic exposure were used, one representing total cumulative exposure (index 1) and the other, intake concentration (index 2). Overall, there was no association of bladder cancer with either measure; however, among smokers, but not among nonsmokers, positive trends in risk were found for exposures estimated for decade-long time periods, especially in the 30- to 39-year period prior to diagnosis. Exposures were in the range 0.5-160 micrograms/liter (mean, 5.0 micrograms/liter). The data raise the possibility that smoking potentiates the effect of arsenic on risk of bladder cancer. However, the risk estimates obtained are much higher than predicted on the basis of the results of the Taiwanese studies, raising concerns about bias or the role of chance. Confirmatory studies are needed.","Case-control study of bladder cancer and arsenic in drinking waterAbs: Mortality from several cancers, including bladder cancer, is elevated in a Taiwanese population exposed to high levels of arsenic in drinking water. Data from the Utah respondents to the National Bladder Cancer Study conducted in 1978 were used to evaluate these associations in a US population exposed to measurable, but much lower, levels of drinking water arsenic. Two indices of cumulative arsenic exposure were used, one representing total cumulative exposure (index 1) and the other, intake concentration (index 2). Overall, there was no association of bladder cancer with either measure; however, among smokers, but not among nonsmokers, positive trends in risk were found for exposures estimated for decade-long time periods, especially in the 30- to 39-year period prior to diagnosis. Exposures were in the range 0.5-160 micrograms/liter (mean, 5.0 micrograms/liter). The data raise the possibility that smoking potentiates the effect of arsenic on risk of bladder cancer. However, the risk estimates obtained are much higher than predicted on the basis of the results of the Taiwanese studies, raising concerns about bias or the role of chance. Confirmatory studies are needed."
428,Bates et al. 2004,Case-control study of bladder cancer and exposure to arsenic in Argentina," Studies have found increased bladder cancer risks associated with high levels of arsenic in drinking water, but little information exists about risks at lower concentrations. Ecologic studies in Argentina have found increased bladder cancer mortality in Córdoba Province, where some wells are contaminated with moderate arsenic concentrations. This population-based bladder cancer case-control study in two Córdoba counties recruited 114 case-control pairs, matched on age, sex, and county, during 1996–2000. Water samples, particularly from wells, were obtained from subjects’ current residences and residences in the last 40 years. Statistical analyses showed no evidence of associations with exposure estimates based on arsenic concentrations in drinking water. However, when well-water consumption per se was used as the exposure measure, time-window analyses suggested that use of well water more than 50 years before interview was associated with increased bladder cancer risk. This association was limited to ever smokers (odds ratio = 2.5, 95% confidence interval: 1.1, 5.5 for 51–70 years before interview), and the possibility that this association is due to chance cannot be excluded. This study suggests lower bladder cancer risks for arsenic than predicted from other studies but adds to evidence that the latency for arsenic-induced bladder cancers may be longer than previously thought.","Case-control study of bladder cancer and exposure to arsenic in ArgentinaAbs: Studies have found increased bladder cancer risks associated with high levels of arsenic in drinking water, but little information exists about risks at lower concentrations. Ecologic studies in Argentina have found increased bladder cancer mortality in Córdoba Province, where some wells are contaminated with moderate arsenic concentrations. This population-based bladder cancer case-control study in two Córdoba counties recruited 114 case-control pairs, matched on age, sex, and county, during 1996–2000. Water samples, particularly from wells, were obtained from subjects’ current residences and residences in the last 40 years. Statistical analyses showed no evidence of associations with exposure estimates based on arsenic concentrations in drinking water. However, when well-water consumption per se was used as the exposure measure, time-window analyses suggested that use of well water more than 50 years before interview was associated with increased bladder cancer risk. This association was limited to ever smokers (odds ratio = 2.5, 95% confidence interval: 1.1, 5.5 for 51–70 years before interview), and the possibility that this association is due to chance cannot be excluded. This study suggests lower bladder cancer risks for arsenic than predicted from other studies but adds to evidence that the latency for arsenic-induced bladder cancers may be longer than previously thought."
429,Beane Freeman et al. 2004,Toenail arsenic content and cutaneous melanoma in Iowa," Cutaneous melanoma has the lowest survival rate of all forms of skin cancer. There has been little research investigating the link between arsenic and cutaneous melanoma, although arsenic has been associated with increased risk of nonmelanoma skin cancer. The authors performed a case-control study examining the association between cutaneous melanoma and environmental arsenic exposure among Iowans aged 40 years or older. Participants included 368 cutaneous melanoma cases and 373 colorectal cancer controls diagnosed in 1999 or 2000, frequency matched on gender and age. Participants completed a mailed survey and submitted toenail clippings for analysis of arsenic content by graphite furnace atomic absorption spectrophotometry. The authors found an increased risk of melanoma for participants with elevated toenail arsenic concentrations (odds ratio = 2.1, 95 percent confidence interval: 1.4, 3.3; p-trend = 0.001) and effect modification by prior skin cancer diagnosis (p-interaction = 0.03). The arsenic-melanoma findings in this study are not known to have been previously reported in observational epidemiologic studies involving incident cutaneous melanoma. Therefore, the findings warrant confirmation.","Toenail arsenic content and cutaneous melanoma in IowaAbs: Cutaneous melanoma has the lowest survival rate of all forms of skin cancer. There has been little research investigating the link between arsenic and cutaneous melanoma, although arsenic has been associated with increased risk of nonmelanoma skin cancer. The authors performed a case-control study examining the association between cutaneous melanoma and environmental arsenic exposure among Iowans aged 40 years or older. Participants included 368 cutaneous melanoma cases and 373 colorectal cancer controls diagnosed in 1999 or 2000, frequency matched on gender and age. Participants completed a mailed survey and submitted toenail clippings for analysis of arsenic content by graphite furnace atomic absorption spectrophotometry. The authors found an increased risk of melanoma for participants with elevated toenail arsenic concentrations (odds ratio = 2.1, 95 percent confidence interval: 1.4, 3.3; p-trend = 0.001) and effect modification by prior skin cancer diagnosis (p-interaction = 0.03). The arsenic-melanoma findings in this study are not known to have been previously reported in observational epidemiologic studies involving incident cutaneous melanoma. Therefore, the findings warrant confirmation."
430,Bears et al. 2006,Arsenic exposure alters hepatic arsenic species composition and stress-mediated gene expression in the common killifish (Fundulus heteroclitus)," In the present paper, we examine how arsenic species accumulate in fish liver and explore the hypothesis that sublethal arsenic concentrations in fish hepatic tissue interfere with stress-mediated gene expression. We exposed killifish (Fundulus heteroclitus) to 787 or 0 microg/L arsenic in tank water for 2 weeks. Arsenic exposure elevated total liver arsenic from 3.4 microg/g wet weight (control fish) to 9.6 microg/g wet weight, and resulted in a higher relative proportion of toxic (e.g. monomethylarsenous acid, dimethylarsenous acid, arsenic V) versus benign (arsenobetaine) arsenic species in this tissue. Following the exposure period, arsenic-treated and control fish were then subjected to a stress protocol: confinement and mechanical chasing for 15 min every 3 h. Liver tissue and blood were sampled from fish not exposed to the stressor at time 0, and at 8, 12, 24 and 40 h following the first stressor. Concentrations of the stress hormone cortisol increased significantly, and glucocorticoid receptor mRNA levels increased and then decreased in both groups, but patterns were nearly identical between arsenic pre-treated and arsenic untreated fish. Prior arsenic exposure prevented the stress-induced increases in stress-responsive LDH-B mRNA levels and enzyme activity observed in fish that had not been exposed to arsenic. However, in another stress-responsive gene, PEPCK, arsenic did not interfere with the stress-induced increase in gene expression, suggesting that the effects of arsenic on stress-mediated gene expression are complex and may involve regulatory pathways that differ between these two genes.","Arsenic exposure alters hepatic arsenic species composition and stress-mediated gene expression in the common killifish (Fundulus heteroclitus)Abs: In the present paper, we examine how arsenic species accumulate in fish liver and explore the hypothesis that sublethal arsenic concentrations in fish hepatic tissue interfere with stress-mediated gene expression. We exposed killifish (Fundulus heteroclitus) to 787 or 0 microg/L arsenic in tank water for 2 weeks. Arsenic exposure elevated total liver arsenic from 3.4 microg/g wet weight (control fish) to 9.6 microg/g wet weight, and resulted in a higher relative proportion of toxic (e.g. monomethylarsenous acid, dimethylarsenous acid, arsenic V) versus benign (arsenobetaine) arsenic species in this tissue. Following the exposure period, arsenic-treated and control fish were then subjected to a stress protocol: confinement and mechanical chasing for 15 min every 3 h. Liver tissue and blood were sampled from fish not exposed to the stressor at time 0, and at 8, 12, 24 and 40 h following the first stressor. Concentrations of the stress hormone cortisol increased significantly, and glucocorticoid receptor mRNA levels increased and then decreased in both groups, but patterns were nearly identical between arsenic pre-treated and arsenic untreated fish. Prior arsenic exposure prevented the stress-induced increases in stress-responsive LDH-B mRNA levels and enzyme activity observed in fish that had not been exposed to arsenic. However, in another stress-responsive gene, PEPCK, arsenic did not interfere with the stress-induced increase in gene expression, suggesting that the effects of arsenic on stress-mediated gene expression are complex and may involve regulatory pathways that differ between these two genes."
431,Mccarty et al. 2007,A case-control study of GST polymorphisms and arsenic related skin lesions," BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10-2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15-3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions.","A case-control study of GST polymorphisms and arsenic related skin lesionsAbs: BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10-2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15-3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions."
432,McCarty et al. 2006,"The impact of diet and betel nut use on skin lesions associated with drinking-water arsenic in Pabna, Bangladesh"," An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water samples were collected. Water samples were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68; 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41; 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89; 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded.","The impact of diet and betel nut use on skin lesions associated with drinking-water arsenic in Pabna, BangladeshAbs: An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water samples were collected. Water samples were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68; 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41; 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89; 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded."
433,Mccarty et al. 2007,"Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions"," OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.","Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesionsAbs: OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals."
434,Mcdonald et al. 2007,Risk of arsenic-related skin lesions in Bangladeshi villages at relatively low exposure: A report from Gonoshasthaya Kendra," OBJECTIVE: Arsenic concentrations in 25% of tube wells in Bangladesh exceed 50 microg/L, a level known to be hazardous. Levels in individual wells vary widely. We gathered data on arsenic exposure levels and skin lesion prevalence to address the lack of knowledge about risks where the average arsenic concentrations was lower. METHODS: The nongovernmental organization Gonoshasthaya Kendra did three related studies of keratotic skin lesions since 2004: (1) an ecological prevalence survey among 13 705 women aged > 18 in a random sample of 53 villages; (2) a case-control study of 176 cases and age- and village-matched referents; and (3) a prevalence survey of the entire population of 11,670 in two additional villages. We calculated prevalence as a function of average arsenic concentrations as reported in the National Hydrochemical Survey, and measured arsenic concentrations in wells used by subjects in the case-control study. FINDINGS: The prevalence of skin lesions was 0.37% in people exposed to arsenic concentrations below 5 microg/L, 0.63% at 6-50 microg/L, and 6.84% at 81 microg/L. In the case-control analysis, relative risk of skin lesions increased threefold at concentrations above 50 microg/L (P < 0.05). CONCLUSION: Little serious skin disease is likely to occur if the arsenic concentration in drinking water is kept below 50 microg/L, but ensuring this water quality will require systematic surveillance and reliable testing of all wells, which may be impractical. More research is needed on feasible prevention of toxic effects from arsenic exposure in Bangladesh.","Risk of arsenic-related skin lesions in Bangladeshi villages at relatively low exposure: A report from Gonoshasthaya KendraAbs: OBJECTIVE: Arsenic concentrations in 25% of tube wells in Bangladesh exceed 50 microg/L, a level known to be hazardous. Levels in individual wells vary widely. We gathered data on arsenic exposure levels and skin lesion prevalence to address the lack of knowledge about risks where the average arsenic concentrations was lower. METHODS: The nongovernmental organization Gonoshasthaya Kendra did three related studies of keratotic skin lesions since 2004: (1) an ecological prevalence survey among 13 705 women aged > 18 in a random sample of 53 villages; (2) a case-control study of 176 cases and age- and village-matched referents; and (3) a prevalence survey of the entire population of 11,670 in two additional villages. We calculated prevalence as a function of average arsenic concentrations as reported in the National Hydrochemical Survey, and measured arsenic concentrations in wells used by subjects in the case-control study. FINDINGS: The prevalence of skin lesions was 0.37% in people exposed to arsenic concentrations below 5 microg/L, 0.63% at 6-50 microg/L, and 6.84% at 81 microg/L. In the case-control analysis, relative risk of skin lesions increased threefold at concentrations above 50 microg/L (P < 0.05). CONCLUSION: Little serious skin disease is likely to occur if the arsenic concentration in drinking water is kept below 50 microg/L, but ensuring this water quality will require systematic surveillance and reliable testing of all wells, which may be impractical. More research is needed on feasible prevention of toxic effects from arsenic exposure in Bangladesh."
435,Meharg et al. 2008,Inorganic arsenic levels in baby rice are of concern," Inorganic arsenic is a chronic exposure carcinogen. Analysis of UK baby rice revealed a median inorganic arsenic content (n=17) of 0.11 mg/kg. By plotting inorganic arsenic against total arsenic, it was found that inorganic concentrations increased linearly up to 0.25 mg/kg total arsenic, then plateaued at 0.16 mg/kg at higher total arsenic concentrations. Inorganic arsenic intake by babies (4-12 months) was considered with respect to current dietary ingestion regulations. It was found that 35% of the baby rice samples analysed would be illegal for sale in China which has regulatory limit of 0.15 mg/kg inorganic arsenic. EU and US food regulations on arsenic are non-existent. When baby inorganic arsenic intake from rice was considered, median consumption (expressed as microg/kg/d) was higher than drinking water maximum exposures predicted for adults in these regions when water intake was expressed on a bodyweight basis.","Inorganic arsenic levels in baby rice are of concernAbs: Inorganic arsenic is a chronic exposure carcinogen. Analysis of UK baby rice revealed a median inorganic arsenic content (n=17) of 0.11 mg/kg. By plotting inorganic arsenic against total arsenic, it was found that inorganic concentrations increased linearly up to 0.25 mg/kg total arsenic, then plateaued at 0.16 mg/kg at higher total arsenic concentrations. Inorganic arsenic intake by babies (4-12 months) was considered with respect to current dietary ingestion regulations. It was found that 35% of the baby rice samples analysed would be illegal for sale in China which has regulatory limit of 0.15 mg/kg inorganic arsenic. EU and US food regulations on arsenic are non-existent. When baby inorganic arsenic intake from rice was considered, median consumption (expressed as microg/kg/d) was higher than drinking water maximum exposures predicted for adults in these regions when water intake was expressed on a bodyweight basis."
436,Bhattacharya and Bhattacharya 2007,Induction of oxidative stress by arsenic in Clarias batrachus: Involvement of peroxisomes," Indian catfish, Clarias batrachus, were exposed to two nonlethal doses of arsenic for 10 days, which induced tissue lipid peroxidation, increased the ratio of oxidized to reduced glutathione and produced excess H(2)O(2) within 1-2 days of exposure. Furthermore, arsenic treatment increased the activity of antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase but decreased glutathione reductase (GR) activity within a day of exposure, indicating the generation of oxidative stress in fish at an early stage. Reversibility of these arsenic-induced responses by pretreatment with N-acetylcysteine indicates that the oxidative stress was due to excess H(2)O(2) production, which was found to be partially contributed by altered H(2)O(2) metabolism in the peroxisomes. It is therefore concluded that peroxisomal H(2)O(2) metabolizing enzymes are potential targets of arsenic toxicity in C. batrachus.","Induction of oxidative stress by arsenic in Clarias batrachus: Involvement of peroxisomesAbs: Indian catfish, Clarias batrachus, were exposed to two nonlethal doses of arsenic for 10 days, which induced tissue lipid peroxidation, increased the ratio of oxidized to reduced glutathione and produced excess H(2)O(2) within 1-2 days of exposure. Furthermore, arsenic treatment increased the activity of antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase but decreased glutathione reductase (GR) activity within a day of exposure, indicating the generation of oxidative stress in fish at an early stage. Reversibility of these arsenic-induced responses by pretreatment with N-acetylcysteine indicates that the oxidative stress was due to excess H(2)O(2) production, which was found to be partially contributed by altered H(2)O(2) metabolism in the peroxisomes. It is therefore concluded that peroxisomal H(2)O(2) metabolizing enzymes are potential targets of arsenic toxicity in C. batrachus."
437,Biswas et al. 2008,Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenic," Over six million people in nine districts of West Bengal, India are exposed to very high levels of arsenic primarily through their drinking water. More than 300,000 people showed arsenic-induced skin lesions in these districts. This is regarded as the greatest arsenic calamity in the world. Chronic arsenicosis causes varied dermatological signs ranging from pigmentation changes, hyperkeratosis to non-melanocytic cancer of skin, and also malignancies in different internal organs. Higher incidences of opportunistic infections are found in the arsenic-exposed individuals, indicating that their immune systems may be impaired somehow. We have thus investigated the effect of arsenic on T-cell proliferation and cytokine secretion in 20 individuals with arsenic-induced skin lesions and compared the results with 18 arsenic-unexposed individuals. A marked dose-dependent suppression of Concanavalin A (Con A) induced T-cell proliferation was observed in the arsenic-exposed individuals compared with the unexposed (P < 0.001) individuals. This correlated with a significant decrease in the levels of secreted cytokines by the T cells (TNF-alpha, IFN-gamma, IL2, IL10, IL5, and IL4) in the exposed individuals (P < 0.001). Thus it can be inferred that arsenic exposure can cause immunosuppression in humans.","Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenicAbs: Over six million people in nine districts of West Bengal, India are exposed to very high levels of arsenic primarily through their drinking water. More than 300,000 people showed arsenic-induced skin lesions in these districts. This is regarded as the greatest arsenic calamity in the world. Chronic arsenicosis causes varied dermatological signs ranging from pigmentation changes, hyperkeratosis to non-melanocytic cancer of skin, and also malignancies in different internal organs. Higher incidences of opportunistic infections are found in the arsenic-exposed individuals, indicating that their immune systems may be impaired somehow. We have thus investigated the effect of arsenic on T-cell proliferation and cytokine secretion in 20 individuals with arsenic-induced skin lesions and compared the results with 18 arsenic-unexposed individuals. A marked dose-dependent suppression of Concanavalin A (Con A) induced T-cell proliferation was observed in the arsenic-exposed individuals compared with the unexposed (P < 0.001) individuals. This correlated with a significant decrease in the levels of secreted cytokines by the T cells (TNF-alpha, IFN-gamma, IL2, IL10, IL5, and IL4) in the exposed individuals (P < 0.001). Thus it can be inferred that arsenic exposure can cause immunosuppression in humans."
438,Bongiovanni et al. 2007,Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells," Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.","Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cellsAbs: Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity."
439,Boonchai et al. 2000,"Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication"," BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs.","Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medicationAbs: BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs."
440,Bosnjak et al. 2008,Selected markers of cardiovascular disease in a population exposed to arsenic from drinking water,"<div>&nbsp;This study examined prevalence and serum levels of selected markers of cardiovascular disease in 34 subjects from a Croatian rural population exposed to high levels of arsenic (As) from drinking water (611.89 +/- 10.06 ug/l). The prevalences of overweight and obese subjects in the population were 32% and 35%. Half the subjects had hypertension, 29% had increased fasting serum glucose level and two were diabetic. Median total cholesterol (5.82 mmol/l) and triglycerides (2.15 mmol/l) were above the desirable margins. The median C-reactive protein level (1.20 mg/l) was slightly higher than previously reported for healthy subjects. Serum Hsp70 level was significantly higher in nonsmokers. Total urinary As levels were positively correlated with age-adjusted serum levels of cobalamin. Near significance were also serum total bilirubin, antibodies to Hsp60 and folate. Tentative investigation of risk factors among subjects classified by tumor necrosis factor-? ?308G/A and interleukin-6-174G/C gene polymorphisms was also performed. Collectively, the results are in agreement with the hypothesis of As-induced and/or compounded cardiovascular disease.</div>","Selected markers of cardiovascular disease in a population exposed to arsenic from drinking waterAbs:<div>&nbsp;This study examined prevalence and serum levels of selected markers of cardiovascular disease in 34 subjects from a Croatian rural population exposed to high levels of arsenic (As) from drinking water (611.89 +/- 10.06 ug/l). The prevalences of overweight and obese subjects in the population were 32% and 35%. Half the subjects had hypertension, 29% had increased fasting serum glucose level and two were diabetic. Median total cholesterol (5.82 mmol/l) and triglycerides (2.15 mmol/l) were above the desirable margins. The median C-reactive protein level (1.20 mg/l) was slightly higher than previously reported for healthy subjects. Serum Hsp70 level was significantly higher in nonsmokers. Total urinary As levels were positively correlated with age-adjusted serum levels of cobalamin. Near significance were also serum total bilirubin, antibodies to Hsp60 and folate. Tentative investigation of risk factors among subjects classified by tumor necrosis factor-? ?308G/A and interleukin-6-174G/C gene polymorphisms was also performed. Collectively, the results are in agreement with the hypothesis of As-induced and/or compounded cardiovascular disease.</div>"
441,Boyce et al. 2008,Probabilistic analysis of human health risks associated with background concentrations of inorganic arsenic: Use of a margin of exposure approach," Substantial evidence exists from epidemiological and mechanistic studies supporting a sublinear or threshold dose-response relationship for the carcinogenicity of ingested arsenic; nonetheless, current regulatory agency evaluations have quantified arsenic risks using default, generic risk assessment procedures that assume a linear, no-threshold dose-response relationship. The resulting slope factors predict risks from U.S. background arsenic exposures that exceed certain regulatory levels of concern, an outcome that presents challenges for risk communication and risk management decisions. To better reflect the available scientific evidence, this article presents the results of a Margin of Exposure (MOE) analysis to characterize risks associated with typical and high-end background exposures of the U.S. population to arsenic from food, water, and soil. MOE values were calculated by comparing a no-observable-adverse-effect-level (NOAEL) derived from the epidemiological literature with exposure estimates generated using a probabilistic (Monte Carlo) model. The plausibility and conservative nature of the exposure and risk estimates evaluated in this analysis are supported by sensitivity and uncertainty analyses and by comparing predicted urinary arsenic concentrations with empirical data. Using the more scientifically supported MOE approach, the analysis presented in this article indicates that typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity.","Probabilistic analysis of human health risks associated with background concentrations of inorganic arsenic: Use of a margin of exposure approachAbs: Substantial evidence exists from epidemiological and mechanistic studies supporting a sublinear or threshold dose-response relationship for the carcinogenicity of ingested arsenic; nonetheless, current regulatory agency evaluations have quantified arsenic risks using default, generic risk assessment procedures that assume a linear, no-threshold dose-response relationship. The resulting slope factors predict risks from U.S. background arsenic exposures that exceed certain regulatory levels of concern, an outcome that presents challenges for risk communication and risk management decisions. To better reflect the available scientific evidence, this article presents the results of a Margin of Exposure (MOE) analysis to characterize risks associated with typical and high-end background exposures of the U.S. population to arsenic from food, water, and soil. MOE values were calculated by comparing a no-observable-adverse-effect-level (NOAEL) derived from the epidemiological literature with exposure estimates generated using a probabilistic (Monte Carlo) model. The plausibility and conservative nature of the exposure and risk estimates evaluated in this analysis are supported by sensitivity and uncertainty analyses and by comparing predicted urinary arsenic concentrations with empirical data. Using the more scientifically supported MOE approach, the analysis presented in this article indicates that typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity."
442,Breton et al. 2006,Gender-specific protective effect of hemoglobin on arsenic-induced skin lesions," Chronic arsenic poisoning remains a public health crisis in Bangladesh. As arsenic has been shown to bind to human hemoglobin (Hb), hematologic mechanisms may play a role in the pathway through which arsenic exerts its toxicity. Two separate studies, a case-control and a cohort, were conducted to investigate the role of Hb in the development of arsenic-induced skin lesions. In the first, conditional logistic regression was used to investigate the effect of Hb on skin lesions among 900 case-control pairs from Pabna, Bangladesh, in which individuals were matched on gender, age, and location. In the second, mixed linear regression models were used to examine the association between toenail arsenic, urinary arsenic, and Hb within a cohort of 184 individuals from 50 families in the same region who did not have arsenic-induced skin lesions. Hb was significantly associated with skin lesions but this association was gender specific. In males, a 40% reduction in the odds of skin lesions occurred for every 1 g/dL increase in Hb (odds ratio, 0.60; 95% confidence interval, 0.49-0.73). No effect was observed for females (odds ratio, 1.16; 95% confidence interval, 0.92-1.46). In the cohort of 184 individuals, no associations between toenail arsenic or urinary arsenic species and Hb levels were observed. Low Hb levels may exacerbate the detrimental health effects of chronic arsenic poisoning. Whereas providing clean water remains the optimal solution to Bangladesh's problem of arsenic poisoning, improving nutrition and reducing iron-deficiency anemia may ameliorate negative health effects, such as skin lesions in individuals who have been exposed.","Gender-specific protective effect of hemoglobin on arsenic-induced skin lesionsAbs: Chronic arsenic poisoning remains a public health crisis in Bangladesh. As arsenic has been shown to bind to human hemoglobin (Hb), hematologic mechanisms may play a role in the pathway through which arsenic exerts its toxicity. Two separate studies, a case-control and a cohort, were conducted to investigate the role of Hb in the development of arsenic-induced skin lesions. In the first, conditional logistic regression was used to investigate the effect of Hb on skin lesions among 900 case-control pairs from Pabna, Bangladesh, in which individuals were matched on gender, age, and location. In the second, mixed linear regression models were used to examine the association between toenail arsenic, urinary arsenic, and Hb within a cohort of 184 individuals from 50 families in the same region who did not have arsenic-induced skin lesions. Hb was significantly associated with skin lesions but this association was gender specific. In males, a 40% reduction in the odds of skin lesions occurred for every 1 g/dL increase in Hb (odds ratio, 0.60; 95% confidence interval, 0.49-0.73). No effect was observed for females (odds ratio, 1.16; 95% confidence interval, 0.92-1.46). In the cohort of 184 individuals, no associations between toenail arsenic or urinary arsenic species and Hb levels were observed. Low Hb levels may exacerbate the detrimental health effects of chronic arsenic poisoning. Whereas providing clean water remains the optimal solution to Bangladesh's problem of arsenic poisoning, improving nutrition and reducing iron-deficiency anemia may ameliorate negative health effects, such as skin lesions in individuals who have been exposed."
443,Brima et al. 2007,Effect of fasting on the pattern of urinary arsenic excretion," Millions of people in some of the poorest regions of the world are exposed to high levels of arsenic through drinking contaminated water. It has been reported that development of cancer caused by arsenic exposure in such populations is dependent on dietary and nutritional factors which can modulate arsenic metabolism. Many people in arsenic exposed regions of Bangladesh and India practice fasting for at least one month every year when they refrain from consumption of food and fluid during daylight hours. How such practices may modulate arsenic metabolism has not been previously investigated. This study investigated this issue by determining total arsenic and its species in urine samples from a group of 29 unexposed volunteers at the beginning of the fasting and at the end of approximately 12 h of fasting period. Inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled with ICP-MS was used to measure the total arsenic and arsenic speciation in the urine samples, respectively. The mean total levels of arsenic at the beginning of fasting (18.3 microg g(-1) creatinine) and at the end of approximately 12 h of fasting (17.7 microg g(-1) creatinine) did not differ significantly (p > 0.05). However, the percentages of urinary arsenic as the methylated arsenic species methylarsonate (MA) were found to be significantly different (p < 0.05) and this species was observed more frequently at the end of fasting, although its overall concentration was similar. There were no significant differences (p > 0.05) in both the concentrations and percentages of other urinary arsenic species detected, namely arsenobetaine (AB) and dimethylarsinate (DMA). Arsenite (As(III)) and arsenate (As(V)) were also analyzed, but were not detected. We conclude that fasting for a period of 12 h results in a significant increase in the percentage of urinary arsenic as MA, and its frequency of detection in the volunteers at the end of the fasting period is almost nine fold higher. This suggests that metabolism of arsenic is altered by fasting.","Effect of fasting on the pattern of urinary arsenic excretionAbs: Millions of people in some of the poorest regions of the world are exposed to high levels of arsenic through drinking contaminated water. It has been reported that development of cancer caused by arsenic exposure in such populations is dependent on dietary and nutritional factors which can modulate arsenic metabolism. Many people in arsenic exposed regions of Bangladesh and India practice fasting for at least one month every year when they refrain from consumption of food and fluid during daylight hours. How such practices may modulate arsenic metabolism has not been previously investigated. This study investigated this issue by determining total arsenic and its species in urine samples from a group of 29 unexposed volunteers at the beginning of the fasting and at the end of approximately 12 h of fasting period. Inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled with ICP-MS was used to measure the total arsenic and arsenic speciation in the urine samples, respectively. The mean total levels of arsenic at the beginning of fasting (18.3 microg g(-1) creatinine) and at the end of approximately 12 h of fasting (17.7 microg g(-1) creatinine) did not differ significantly (p > 0.05). However, the percentages of urinary arsenic as the methylated arsenic species methylarsonate (MA) were found to be significantly different (p < 0.05) and this species was observed more frequently at the end of fasting, although its overall concentration was similar. There were no significant differences (p > 0.05) in both the concentrations and percentages of other urinary arsenic species detected, namely arsenobetaine (AB) and dimethylarsinate (DMA). Arsenite (As(III)) and arsenate (As(V)) were also analyzed, but were not detected. We conclude that fasting for a period of 12 h results in a significant increase in the percentage of urinary arsenic as MA, and its frequency of detection in the volunteers at the end of the fasting period is almost nine fold higher. This suggests that metabolism of arsenic is altered by fasting."
444,Meacher et al. 2002,Estimation of multimedia inorganic arsenic intake in the US population," Arsenic is widely distributed in the environment by natural and human means. The potential for adverse health effects from inorganic arsenic depends on the level and route of exposure. To estimate potential health risks of inorganic arsenic, the apportionment of exposure among sources of inorganic arsenic is critical. In this study, daily inorganic arsenic intake of U.S. adults from food, water, and soil ingestion and from airborne particle inhalation was estimated. To account for variations in exposure across the U.S., a Monte Carlo approach was taken using simulations for 100,000 individuals representing the age, gender, and county of residence of the U.S. population based on census data. Our analysis found that food is the greatest source of inorganic arsenic intake and that drinking water is the next highest contributor. Inhalation of airborne arsenic-containing particles and ingestion of arsenic-containing soils were negligible contributors. The exposure is best represented by the ranges of inorganic arsenic intake (at the 10th and 90th percentiles), which were 1.8 to 11.4 µg/day for males and 1.3 to 9.4 µg/day for females. Regional differences in inorganic arsenic exposure were due mostly to consumption of drinking water containing differing inorganic arsenic content rather than to food preferences.","Estimation of multimedia inorganic arsenic intake in the US populationAbs: Arsenic is widely distributed in the environment by natural and human means. The potential for adverse health effects from inorganic arsenic depends on the level and route of exposure. To estimate potential health risks of inorganic arsenic, the apportionment of exposure among sources of inorganic arsenic is critical. In this study, daily inorganic arsenic intake of U.S. adults from food, water, and soil ingestion and from airborne particle inhalation was estimated. To account for variations in exposure across the U.S., a Monte Carlo approach was taken using simulations for 100,000 individuals representing the age, gender, and county of residence of the U.S. population based on census data. Our analysis found that food is the greatest source of inorganic arsenic intake and that drinking water is the next highest contributor. Inhalation of airborne arsenic-containing particles and ingestion of arsenic-containing soils were negligible contributors. The exposure is best represented by the ranges of inorganic arsenic intake (at the 10th and 90th percentiles), which were 1.8 to 11.4 µg/day for males and 1.3 to 9.4 µg/day for females. Regional differences in inorganic arsenic exposure were due mostly to consumption of drinking water containing differing inorganic arsenic content rather than to food preferences."
445,Meliker et al. 2007,"Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: A standardized mortality ratio analysis"," BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 microg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10-100 microg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population-weighted mean arsenic concentration of 11.00 microg/L and a population-weighted median of 7.58 microg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09-1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14-1.25; F SMR, 1.19; CI, 1.15-1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18-1.37; F SMR, 1.27; CI, 1.19-1.35), and kidney diseases (M SMR, 1.28; CI, 1.15-1.42; F SMR, 1.38; CI, 1.25-1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis.","Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: A standardized mortality ratio analysisAbs: BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 microg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10-100 microg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population-weighted mean arsenic concentration of 11.00 microg/L and a population-weighted median of 7.58 microg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09-1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14-1.25; F SMR, 1.19; CI, 1.15-1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18-1.37; F SMR, 1.27; CI, 1.19-1.35), and kidney diseases (M SMR, 1.28; CI, 1.15-1.42; F SMR, 1.38; CI, 1.25-1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis."
446,Meza et al. 2004,"Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico"," The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.","Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, MexicoAbs: The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations."
447,Michaud et al. 2004,Arsenic concentrations in prediagnostic toenails and the risk of bladder cancer in a cohort study of male smokers," At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (<100 µg/liter) is related to bladder cancer risk. No study has been known to use biomarkers to assess the relation between individual arsenic exposure and bladder cancer risk. Toenail samples provide an integrated measure of internal arsenic exposure and reflect long-term exposure. The authors examined the relation between toenail arsenic levels and bladder cancer risk among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort of Finnish male smokers aged 50–69 years. Data for 280 incident bladder cancer cases, identified between baseline (1985–1988) and April 1999, were available for analysis. One control was matched to each case on the basis of age, toenail collection date, intervention group, and smoking duration. Arsenic levels in toenail samples were determined by using neutron activation analysis. Logistic regression analyses were performed to estimate odds ratios. Arsenic toenail concentrations in this Finnish study were similar to those reported in US studies (range: 0.02–17.5 µg/g). The authors observed no association between inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95% confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These findings suggest that low-level arsenic exposure is unlikely to explain a substantial excess risk of bladder cancer.","Arsenic concentrations in prediagnostic toenails and the risk of bladder cancer in a cohort study of male smokersAbs: At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (<100 µg/liter) is related to bladder cancer risk. No study has been known to use biomarkers to assess the relation between individual arsenic exposure and bladder cancer risk. Toenail samples provide an integrated measure of internal arsenic exposure and reflect long-term exposure. The authors examined the relation between toenail arsenic levels and bladder cancer risk among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort of Finnish male smokers aged 50–69 years. Data for 280 incident bladder cancer cases, identified between baseline (1985–1988) and April 1999, were available for analysis. One control was matched to each case on the basis of age, toenail collection date, intervention group, and smoking duration. Arsenic levels in toenail samples were determined by using neutron activation analysis. Logistic regression analyses were performed to estimate odds ratios. Arsenic toenail concentrations in this Finnish study were similar to those reported in US studies (range: 0.02–17.5 µg/g). The authors observed no association between inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95% confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These findings suggest that low-level arsenic exposure is unlikely to explain a substantial excess risk of bladder cancer."
448,Miller et al. 2007,MRP2 and acquired tolerance to inorganic arsenic in the kidney of killifish (Fundulus heteroclitus)," We used proximal tubules isolated from the killifish, Fundulus heteroclitus, to examine the effect of environmentally relevant, sublethal levels of arsenic on the function and expression of MRP2, an ABC transporter that transports xenobiotics into urine, including arsenic-glutathione conjugates. Exposure of fish to arsenic as sodium arsenite (4-14 days) increased both MRP2 expression in the apical membrane of proximal tubules and MRP2-mediated transport activity. The level of MRP2 mRNA was not affected, suggesting a posttranslational mechanism of action. Acute exposure of proximal tubules isolated from control fish to 75-375 ppb arsenic decreased mitochondrial function (inner membrane electrical potential). However, in tubules from fish that were preexposed to arsenic (4-14 days), no such effect on mitochondrial function was observed. Thus, chronic in vivo exposure to arsenic induces mechanisms that protect proximal tubules during subsequent arsenic exposure. Upregulation of MRP2 expression and activity is one likely contributing factor.","MRP2 and acquired tolerance to inorganic arsenic in the kidney of killifish (Fundulus heteroclitus)Abs: We used proximal tubules isolated from the killifish, Fundulus heteroclitus, to examine the effect of environmentally relevant, sublethal levels of arsenic on the function and expression of MRP2, an ABC transporter that transports xenobiotics into urine, including arsenic-glutathione conjugates. Exposure of fish to arsenic as sodium arsenite (4-14 days) increased both MRP2 expression in the apical membrane of proximal tubules and MRP2-mediated transport activity. The level of MRP2 mRNA was not affected, suggesting a posttranslational mechanism of action. Acute exposure of proximal tubules isolated from control fish to 75-375 ppb arsenic decreased mitochondrial function (inner membrane electrical potential). However, in tubules from fish that were preexposed to arsenic (4-14 days), no such effect on mitochondrial function was observed. Thus, chronic in vivo exposure to arsenic induces mechanisms that protect proximal tubules during subsequent arsenic exposure. Upregulation of MRP2 expression and activity is one likely contributing factor."
449,Bunderson et al. 2004,Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis," A correlation between arsenic and cardiovascular disease (CVD) has been established through epidemiological studies, although the mechanisms are unknown. Using a mouse model that develops atherosclerotic lesions on a normal chow diet, we have confirmed a connection between long-term arsenic intake and CVD. Our results reveal a significant increase in the degree of atherosclerotic plaque stenosis within the innominate artery of ApoE-/-/LDLr-/- mice treated with 10 ppm sodium arsenite (133 microM) in drinking water for 18 weeks compared to controls. Immunohistochemistry shows nitrotyrosine formation, a marker of reactive nitrogen species generation, is significantly higher within the atherosclerotic plaque of arsenic-treated mice. In addition, there is a significant increase in the 5-lipoxygenase (5-LO) product, leukotriene E4 (LTE4), in the serum of arsenic-treated mice. This is supported by induction of the 5-LO protein and subsequent increases in LTE4 synthesis in bovine aortic endothelial cells. This increase in LTE4 is partially inhibited by inhibitors of nitric oxide synthase, suggesting a link between reactive nitrogen species and arsenic-induced inflammation. Furthermore, there is a significant increase in prostacyclin (PGI2) in the serum of arsenic-treated mice. We conclude that changes in specific inflammatory mediators such as LTE4 and PGI2 are related to arsenic-induced atherosclerosis. In addition, amplified synthesis of reactive species such as peroxynitrite results in increased protein nitration in response to arsenic exposure. This finding is consistent with the pathology seen in human atherosclerotic plaques.","Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesisAbs: A correlation between arsenic and cardiovascular disease (CVD) has been established through epidemiological studies, although the mechanisms are unknown. Using a mouse model that develops atherosclerotic lesions on a normal chow diet, we have confirmed a connection between long-term arsenic intake and CVD. Our results reveal a significant increase in the degree of atherosclerotic plaque stenosis within the innominate artery of ApoE-/-/LDLr-/- mice treated with 10 ppm sodium arsenite (133 microM) in drinking water for 18 weeks compared to controls. Immunohistochemistry shows nitrotyrosine formation, a marker of reactive nitrogen species generation, is significantly higher within the atherosclerotic plaque of arsenic-treated mice. In addition, there is a significant increase in the 5-lipoxygenase (5-LO) product, leukotriene E4 (LTE4), in the serum of arsenic-treated mice. This is supported by induction of the 5-LO protein and subsequent increases in LTE4 synthesis in bovine aortic endothelial cells. This increase in LTE4 is partially inhibited by inhibitors of nitric oxide synthase, suggesting a link between reactive nitrogen species and arsenic-induced inflammation. Furthermore, there is a significant increase in prostacyclin (PGI2) in the serum of arsenic-treated mice. We conclude that changes in specific inflammatory mediators such as LTE4 and PGI2 are related to arsenic-induced atherosclerosis. In addition, amplified synthesis of reactive species such as peroxynitrite results in increased protein nitration in response to arsenic exposure. This finding is consistent with the pathology seen in human atherosclerotic plaques."
450,Bunderson et al. 2006,Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenic," Long-term exposure to arsenic in drinking water has been linked to cancer and other health effects, including cardiovascular disease. Arsenic in the environment is found in combination with a range of metals that could influence its toxicity. Manganese, in particular, is a metal that is typically found in conjunction with arsenic in contaminated groundwater. Peroxynitrite is a powerful oxidant formed from the reaction between nitric oxide and superoxide anion. Arsenic has been shown to increase the formation of peroxynitrite in bovine aortic endothelial cells (BAECs) and promote the formation of 3-nitrotyrosine (3-NY) in the atherosclerotic plaque of ApoE-/-/LDLr-/- mice. Arsenic exposure also increases leukotriene E4 (LTE4) formation in both the mice and BAECs, an effect that is partially reversed by the addition of Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. In the present study, we investigated the effect of adding nontoxic concentrations of manganese along with arsenic to BAEC cultures. Manganese increased arsenic toxicity and enhanced peroxynitrite, 3-NY, and LTE4 formation in BAECs. Addition of LNAME reduced 3-NY formation induced by arsenic/manganese mixtures, but in contrast to its effect on arsenic alone, L-NAME actually increased LTE4 synthesis in BAECs treated with the arsenic/manganese combination. Overall, these data suggest that manganese may exacerbate the toxic effects of arsenic on the vascular system.","Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenicAbs: Long-term exposure to arsenic in drinking water has been linked to cancer and other health effects, including cardiovascular disease. Arsenic in the environment is found in combination with a range of metals that could influence its toxicity. Manganese, in particular, is a metal that is typically found in conjunction with arsenic in contaminated groundwater. Peroxynitrite is a powerful oxidant formed from the reaction between nitric oxide and superoxide anion. Arsenic has been shown to increase the formation of peroxynitrite in bovine aortic endothelial cells (BAECs) and promote the formation of 3-nitrotyrosine (3-NY) in the atherosclerotic plaque of ApoE-/-/LDLr-/- mice. Arsenic exposure also increases leukotriene E4 (LTE4) formation in both the mice and BAECs, an effect that is partially reversed by the addition of Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. In the present study, we investigated the effect of adding nontoxic concentrations of manganese along with arsenic to BAEC cultures. Manganese increased arsenic toxicity and enhanced peroxynitrite, 3-NY, and LTE4 formation in BAECs. Addition of LNAME reduced 3-NY formation induced by arsenic/manganese mixtures, but in contrast to its effect on arsenic alone, L-NAME actually increased LTE4 synthesis in BAECs treated with the arsenic/manganese combination. Overall, these data suggest that manganese may exacerbate the toxic effects of arsenic on the vascular system."
451,Burns et al. 2004,Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: A dose-response study," The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experiment ended at 182 days. Untreated mice and mice fed only arsenite developed no tumors. In the remaining groups a total of 322 locally invasive squamous carcinomas occurred. The carcinoma yield in mice exposed only to UVR was 2.4 +/- 0.5 cancers/mouse at 182 days. Dietary arsenite markedly enhanced the UVR-induced cancer yield in a pattern consistent with linearity up to a peak of 11.1 +/- 1.0 cancers/mouse at 5.0 mg/L arsenite, representing a peak enhancement ratio of 4.63 +/- 1.05. A decline occurred to 6.8 +/- 0.8 cancers/mouse at 10.0 mg/L arsenite. New cancer rates exhibited a consistent-with-linear dependence on time beginning after initial cancer-free intervals ranging between 88 and 95 days. Epidermal hyperplasia was elevated by arsenite alone and UVR alone and was greater than additive for the combined exposures as were growth rates of the cancers. These results demonstrate the usefulness of a new animal model for studying the carcinogenic action of dietary arsenite on skin exposed to UVR and should contribute to understanding how to make use of animal data for assessment of human cancer risks in tissues exposed to mixtures of carcinogens and cancer-enhancing agents.","Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: A dose-response studyAbs: The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experiment ended at 182 days. Untreated mice and mice fed only arsenite developed no tumors. In the remaining groups a total of 322 locally invasive squamous carcinomas occurred. The carcinoma yield in mice exposed only to UVR was 2.4 +/- 0.5 cancers/mouse at 182 days. Dietary arsenite markedly enhanced the UVR-induced cancer yield in a pattern consistent with linearity up to a peak of 11.1 +/- 1.0 cancers/mouse at 5.0 mg/L arsenite, representing a peak enhancement ratio of 4.63 +/- 1.05. A decline occurred to 6.8 +/- 0.8 cancers/mouse at 10.0 mg/L arsenite. New cancer rates exhibited a consistent-with-linear dependence on time beginning after initial cancer-free intervals ranging between 88 and 95 days. Epidermal hyperplasia was elevated by arsenite alone and UVR alone and was greater than additive for the combined exposures as were growth rates of the cancers. These results demonstrate the usefulness of a new animal model for studying the carcinogenic action of dietary arsenite on skin exposed to UVR and should contribute to understanding how to make use of animal data for assessment of human cancer risks in tissues exposed to mixtures of carcinogens and cancer-enhancing agents."
452,Caceres et al. 2005,Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population," The relationship of inorganic arsenic exposure through drinking water and total urinary arsenic excretion in a nonoccupationally exposed population was evaluated in a cross-sectional study in three mayor cities of Chile (Antofagasta, Santiago, and Temuco). A total of 756 individuals in three population strata (elderly, students, and workers) provided first morning void urine specimens the day after exposure and food surveys were administered. Arsenic intake from drinking water was estimated from analysis of tap water samples, plus 24-h dietary recall and food frequency questionnaires. Multilevel analysis was used to evaluate the effects of the age group and city factors adjusted by predictor variables. Arsenic levels in drinking water and urine were significantly higher in Antofagasta compared with the other cities. City-and individual-level factors, 12% and 88%, respectively, accounted for the variability in urinary arsenic concentration. The main predictors of urinary arsenic concentration were total arsenic consumption through water and age. These findings indicate that arsenic concentration in drinking water continues to be the principal contributing factor to exposure to inorganic arsenic in the Chilean population.","Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean populationAbs: The relationship of inorganic arsenic exposure through drinking water and total urinary arsenic excretion in a nonoccupationally exposed population was evaluated in a cross-sectional study in three mayor cities of Chile (Antofagasta, Santiago, and Temuco). A total of 756 individuals in three population strata (elderly, students, and workers) provided first morning void urine specimens the day after exposure and food surveys were administered. Arsenic intake from drinking water was estimated from analysis of tap water samples, plus 24-h dietary recall and food frequency questionnaires. Multilevel analysis was used to evaluate the effects of the age group and city factors adjusted by predictor variables. Arsenic levels in drinking water and urine were significantly higher in Antofagasta compared with the other cities. City-and individual-level factors, 12% and 88%, respectively, accounted for the variability in urinary arsenic concentration. The main predictors of urinary arsenic concentration were total arsenic consumption through water and age. These findings indicate that arsenic concentration in drinking water continues to be the principal contributing factor to exposure to inorganic arsenic in the Chilean population."
453,Calderon et al. 2004,Consequences of acute and chronic exposure to arsenic in children," Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. For most people, the major exposure to arsenic comes from food (8 to 14 microg inorganic arsenic per day), but when the arsenic level in water is elevated, drinking water becomes the predominant source of exposure. Because it is very difficult to limit arsenic exposure from food, it would be wise to limit arsenic exposure from those more controllable sources. Pediatricians should ascertain the levels of arsenic in drinking water of patients with high arsenic levels, using the supplier or, in the case of private wells, a professional water-testing laboratory assay. The Safe Drinking Water Act does not cover private wells or those water systems with less than 15 hook-ups or those that serve less than 25 people. Pediatricians should instruct parents to use prepared baby formulas or prepare them using water with the arsenic removed and to curtail playing time for younger children in places that have sand containing large amounts of arsenic. Such procedures will limit arsenic exposure to a minimum.","Consequences of acute and chronic exposure to arsenic in childrenAbs: Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. For most people, the major exposure to arsenic comes from food (8 to 14 microg inorganic arsenic per day), but when the arsenic level in water is elevated, drinking water becomes the predominant source of exposure. Because it is very difficult to limit arsenic exposure from food, it would be wise to limit arsenic exposure from those more controllable sources. Pediatricians should ascertain the levels of arsenic in drinking water of patients with high arsenic levels, using the supplier or, in the case of private wells, a professional water-testing laboratory assay. The Safe Drinking Water Act does not cover private wells or those water systems with less than 15 hook-ups or those that serve less than 25 people. Pediatricians should instruct parents to use prepared baby formulas or prepare them using water with the arsenic removed and to curtail playing time for younger children in places that have sand containing large amounts of arsenic. Such procedures will limit arsenic exposure to a minimum."
454,Calderon et al. 1999,Excretion of arsenic in urine as a function of exposure to arsenic in drinking water," Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first morning urine voids for up to 5 consecutive days. The study population was 56% male, and 44% was younger than 18 years of age. On one day of the study period, all voided urines were collected over a 24-hr period. Arsenic intake from drinking water was estimated from daily food diaries. Comparison between the concentration of As in individual urine voids with that in the 24-hr urine collection indicated that the concentration of As in urine was stable throughout the day. Comparison of the concentration of As in each first morning urine void over the 5-day study period indicated that there was little day-to-day variation in the concentration of As in urine. The concentration of As in drinking water was a better predictor of the concentration of As in urine than was the estimated intake of As from drinking water. The concentration of As in urine did not vary by gender. An age-dependent difference in the concentration of As in urine may be attributed to the higher As dosage rate per unit body weight in children than in adults. These findings suggest that the analysis of a small number of urine samples may be adequate to estimate an individual's exposure to InAs from drinking water and that the determination of the concentration of InAs in a drinking water supply may be a useful surrogate for estimating exposure to this metalloid.","Excretion of arsenic in urine as a function of exposure to arsenic in drinking waterAbs: Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first morning urine voids for up to 5 consecutive days. The study population was 56% male, and 44% was younger than 18 years of age. On one day of the study period, all voided urines were collected over a 24-hr period. Arsenic intake from drinking water was estimated from daily food diaries. Comparison between the concentration of As in individual urine voids with that in the 24-hr urine collection indicated that the concentration of As in urine was stable throughout the day. Comparison of the concentration of As in each first morning urine void over the 5-day study period indicated that there was little day-to-day variation in the concentration of As in urine. The concentration of As in drinking water was a better predictor of the concentration of As in urine than was the estimated intake of As from drinking water. The concentration of As in urine did not vary by gender. An age-dependent difference in the concentration of As in urine may be attributed to the higher As dosage rate per unit body weight in children than in adults. These findings suggest that the analysis of a small number of urine samples may be adequate to estimate an individual's exposure to InAs from drinking water and that the determination of the concentration of InAs in a drinking water supply may be a useful surrogate for estimating exposure to this metalloid."
455,Centeno et al. 2002,Pathology related to chronic arsenic exposure," Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water.","Pathology related to chronic arsenic exposureAbs: Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water."
456,Chakraborti et al. 2004,Groundwater arsenic contamination and its health effects in the Ganga-Meghna-Brahmaputra plain," The opinions expressed in the following article are entirely those of the author and do not necessarily represent the views of either the Royal Society of Chemistry, the Editor or the Editorial Board of JEM.","Groundwater arsenic contamination and its health effects in the Ganga-Meghna-Brahmaputra plainAbs: The opinions expressed in the following article are entirely those of the author and do not necessarily represent the views of either the Royal Society of Chemistry, the Editor or the Editorial Board of JEM."
457,Chanda et al. 2006,DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy," Chronic arsenic exposure is known to produce arsenicosis and cancer. To ascertain whether perturbation of methylation plays a role in such carcinogenesis, the degree of methylation of p53 and p16 gene in DNA obtained from blood samples of people chronically exposed to arsenic and skin cancer subjects was studied. Methylation-specific restriction endonuclease digestion followed by polymerase chain reaction (PCR) of gene p53 and bisulfite treatment followed by methylation-sensitive PCR of gene p16 have been carried out to analyze the methylation status of the samples studied. Significant DNA hypermethylation of promoter region of p53 gene was observed in DNA of arsenic-exposed people compared to control subjects. This hypermethylation showed a dose-response relationship. Further, hypermethylation of p53 gene was also observed in arsenic-induced skin cancer patients compared to subjects having skin cancer unrelated to arsenic, though not at significant level. However, a small subgroup of cases showed hypomethylation with high arsenic exposure. Significant hypermethylation of gene p16 was also observed in cases of arsenicosis exposed to high level of arsenic. In man, arsenic has the ability to alter DNA methylation patterns in gene p53 and p16, which are important in carcinogenesis.","DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancyAbs: Chronic arsenic exposure is known to produce arsenicosis and cancer. To ascertain whether perturbation of methylation plays a role in such carcinogenesis, the degree of methylation of p53 and p16 gene in DNA obtained from blood samples of people chronically exposed to arsenic and skin cancer subjects was studied. Methylation-specific restriction endonuclease digestion followed by polymerase chain reaction (PCR) of gene p53 and bisulfite treatment followed by methylation-sensitive PCR of gene p16 have been carried out to analyze the methylation status of the samples studied. Significant DNA hypermethylation of promoter region of p53 gene was observed in DNA of arsenic-exposed people compared to control subjects. This hypermethylation showed a dose-response relationship. Further, hypermethylation of p53 gene was also observed in arsenic-induced skin cancer patients compared to subjects having skin cancer unrelated to arsenic, though not at significant level. However, a small subgroup of cases showed hypomethylation with high arsenic exposure. Significant hypermethylation of gene p16 was also observed in cases of arsenicosis exposed to high level of arsenic. In man, arsenic has the ability to alter DNA methylation patterns in gene p53 and p16, which are important in carcinogenesis."
458,Chang et al. 2004,Ischemic heart disease mortality reduction in an arseniasis-endemic area in southwestern Taiwan after a switch in the tap-water supply system," Arsenic has been identified as a major contributing risk factor for development of blackfoot disease (BFD), a unique peripheral vascular disease that was endemic to the southwestern coast of Taiwan, where residents imbibed artesian well water continuing high amounts of arsenic for more than 50 yr. Chronic arsenic exposure was found to be associated with ischemic heart disease (CHD) in a dose-dependent manner. A tap-water supply system was implemented in the early 1960s in the BFD-endemic areas. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to examine whether CHD-related mortality decreased after consumption of high-arsenic-containing artesian well water ceased and, if so, when the reduction occurred. Standardized mortality ratios (SMRs) for CHD were calculated for the BFD endemic area for the years 1971-2000. Cumulative-sum techniques were used to detect the occurrence of changes in the SMRs. Data show that mortality attributed to CHD declined gradually for approximately 17 to 20 yr following cessation of consumption of high-arsenic artesian well water. Based on the reversibility criterion, the association between arsenic exposure an1rd CHD-related mortality is likely to be causal. Copyright Taylor & Francis Inc.","Ischemic heart disease mortality reduction in an arseniasis-endemic area in southwestern Taiwan after a switch in the tap-water supply systemAbs: Arsenic has been identified as a major contributing risk factor for development of blackfoot disease (BFD), a unique peripheral vascular disease that was endemic to the southwestern coast of Taiwan, where residents imbibed artesian well water continuing high amounts of arsenic for more than 50 yr. Chronic arsenic exposure was found to be associated with ischemic heart disease (CHD) in a dose-dependent manner. A tap-water supply system was implemented in the early 1960s in the BFD-endemic areas. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to examine whether CHD-related mortality decreased after consumption of high-arsenic-containing artesian well water ceased and, if so, when the reduction occurred. Standardized mortality ratios (SMRs) for CHD were calculated for the BFD endemic area for the years 1971-2000. Cumulative-sum techniques were used to detect the occurrence of changes in the SMRs. Data show that mortality attributed to CHD declined gradually for approximately 17 to 20 yr following cessation of consumption of high-arsenic artesian well water. Based on the reversibility criterion, the association between arsenic exposure an1rd CHD-related mortality is likely to be causal. Copyright Taylor & Francis Inc."
459,Chang et al. 1991,Higher prevalence of goiter in endemic area of blackfoot disease in Taiwan," Blackfoot disease is an endemic peripheral vascular disorder which is confined to a limited land area on the southwest coast of Taiwan. It has long been related to the consumption of high levels of arsenic found in the artesian well water. Humic substances have also been extracted from the well water and have been reported as a possible source of environmental goitrogen. The purpose of this study was to examine whether the prevalence of goiter is increased in the blackfoot disease-endemic area. This study covered all the children in the elementary schools of Putai and Peimen. They were divided into two groups according to the location of schools in the endemic area or non-endemic area of blackfoot disease. Thyroid enlargement was examined by palpation as recommended by the World Health Organization. Thyroid antibodies and hormones were determined in school children with a goiter and age-sex-matched normal control children using particle agglutination methods and radioimmunoassays, respectively. Aspiration cytology was done in cases with a nodular goiter. In total 4,567 school children were examined, including 2,306 males and 2,261 females. One hundred and twenty school children (2.63%) had a goiter of grade I or above. The prevalence of goiters in school children from the endemic area was higher than that from the non-endemic area (3.44 vs 2.08%, p less than 0.01). The prevalence of goiters in females from the endemic area was higher than that from the non-endemic area (4.65 vs 2.69%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)","Higher prevalence of goiter in endemic area of blackfoot disease in TaiwanAbs: Blackfoot disease is an endemic peripheral vascular disorder which is confined to a limited land area on the southwest coast of Taiwan. It has long been related to the consumption of high levels of arsenic found in the artesian well water. Humic substances have also been extracted from the well water and have been reported as a possible source of environmental goitrogen. The purpose of this study was to examine whether the prevalence of goiter is increased in the blackfoot disease-endemic area. This study covered all the children in the elementary schools of Putai and Peimen. They were divided into two groups according to the location of schools in the endemic area or non-endemic area of blackfoot disease. Thyroid enlargement was examined by palpation as recommended by the World Health Organization. Thyroid antibodies and hormones were determined in school children with a goiter and age-sex-matched normal control children using particle agglutination methods and radioimmunoassays, respectively. Aspiration cytology was done in cases with a nodular goiter. In total 4,567 school children were examined, including 2,306 males and 2,261 females. One hundred and twenty school children (2.63%) had a goiter of grade I or above. The prevalence of goiters in school children from the endemic area was higher than that from the non-endemic area (3.44 vs 2.08%, p less than 0.01). The prevalence of goiters in females from the endemic area was higher than that from the non-endemic area (4.65 vs 2.69%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)"
460,Chen and Ahsan 2004,Cancer burden from arsenic in drinking water in Bangladesh," We assessed the potential burden of internal cancers due to arsenic exposure in Bangladesh. We estimated excess lifetime risks of death from liver, bladder, and lung cancers using an exposure distribution, death probabilities, and cancer mortality rates from Bangladesh and dose-specific relative risk estimates from Taiwan. Results indicated at least a doubling of lifetime mortality risk from liver, bladder, and lung cancers (229.6 vs 103.5 per 100 000 population) in Bangladesh owing to arsenic in drinking water.","Cancer burden from arsenic in drinking water in BangladeshAbs: We assessed the potential burden of internal cancers due to arsenic exposure in Bangladesh. We estimated excess lifetime risks of death from liver, bladder, and lung cancers using an exposure distribution, death probabilities, and cancer mortality rates from Bangladesh and dose-specific relative risk estimates from Taiwan. Results indicated at least a doubling of lifetime mortality risk from liver, bladder, and lung cancers (229.6 vs 103.5 per 100 000 population) in Bangladesh owing to arsenic in drinking water."
461,Chen and Wang 1990,Ecological correlation between arsenic level in well water and age-adjusted mortality from malignant neoplasms," A significant dose-response relation between ingested arsenic and several cancers has recently been reported in four townships of the endemic area of blackfoot disease, a unique peripheral artery disease related to the chronic arsenic exposure in southwestern Taiwan. This study was carried out to examine ecological correlations between arsenic level of well water and mortality from various malignant neoplasms in 314 precincts and townships of Taiwan. The arsenic content in water of 83,656 wells was determined by a standard mercuric bromide stain method from 1974 to 1976, while mortality rates of 21 malignant neoplasms among residents in study precincts and townships from 1972 to 1983 were standardized to the world population in 1976. A significant association with the arsenic level in well water was observed for cancers of the liver, nasal cavity, lung, skin, bladder and kidney in both males and females as well as for the prostate cancer in males. These associations remained significant after adjusting for indices of urbanization and industrialization through multiple regression analyses. The multivariate-adjusted regression coefficient indicating an increase in age-adjusted mortality per 100,000 person-years for every 0.1 ppm increase in arsenic level of well water was 6.8 and 2.0, 0.7 and 0.4, 5.3 and 5.3, 0.9 and 1.0, 3.9 and 4.2, as well as 1.1 and 1.7, respectively, in males and females for cancers of the liver, nasal cavity, lung, skin, bladder and kidney. The multivariate-adjusted regression coefficient for the prostate cancer was 0.5. These weighted regression coefficients were found to increase or remain unchanged in further analyses in which only 170 southwestern townships were included.","Ecological correlation between arsenic level in well water and age-adjusted mortality from malignant neoplasmsAbs: A significant dose-response relation between ingested arsenic and several cancers has recently been reported in four townships of the endemic area of blackfoot disease, a unique peripheral artery disease related to the chronic arsenic exposure in southwestern Taiwan. This study was carried out to examine ecological correlations between arsenic level of well water and mortality from various malignant neoplasms in 314 precincts and townships of Taiwan. The arsenic content in water of 83,656 wells was determined by a standard mercuric bromide stain method from 1974 to 1976, while mortality rates of 21 malignant neoplasms among residents in study precincts and townships from 1972 to 1983 were standardized to the world population in 1976. A significant association with the arsenic level in well water was observed for cancers of the liver, nasal cavity, lung, skin, bladder and kidney in both males and females as well as for the prostate cancer in males. These associations remained significant after adjusting for indices of urbanization and industrialization through multiple regression analyses. The multivariate-adjusted regression coefficient indicating an increase in age-adjusted mortality per 100,000 person-years for every 0.1 ppm increase in arsenic level of well water was 6.8 and 2.0, 0.7 and 0.4, 5.3 and 5.3, 0.9 and 1.0, 3.9 and 4.2, as well as 1.1 and 1.7, respectively, in males and females for cancers of the liver, nasal cavity, lung, skin, bladder and kidney. The multivariate-adjusted regression coefficient for the prostate cancer was 0.5. These weighted regression coefficients were found to increase or remain unchanged in further analyses in which only 170 southwestern townships were included."
462,Chen et al. 2007,"Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: A population-based, cross-sectional study"," The authors performed a cross-sectional analysis to evaluate the association between arsenic exposure from drinking water and blood pressure using baseline data of 10,910 participants in the Health Effects of Arsenic Longitudinal Study in Bangladesh (October 2000-May 2002). A time-weighted well arsenic concentration (TWA) based on current and past use of drinking wells was derived. Odds ratios for high pulse pressure (> or = 55 mmHg) by increasing TWA quintiles (< or = 8, 8.1-40.8, 40.9-91.0, 91.1-176.0, and 176.1-864.0 microg/liter) were 1.00 (referent), 1.39 (95% confidence interval (CI): 1.14, 1.71), 1.21 (95% CI: 0.99, 1.49), 1.19 (95% CI: 0.97, 1.45), and 1.19 (95% CI: 0.97, 1.46). Among participants with a lower than average dietary intake level of B vitamins and folate, the odds ratios for high pulse pressure by increasing TWA quintiles were 1.00 (referent), 1.84 (95% CI: 1.07, 3.16), 1.89 (95% CI: 1.11, 3.20), 1.83 (95% CI: 1.09, 3.07), and 1.89 (95% CI: 1.12, 3.20). The odds ratios for systolic hypertension suggest a similar but weaker association. No apparent associations were observed between TWA and general or diastolic hypertension. These findings indicate that the effect of low-level arsenic exposure on blood pressure is nonlinear and may be more pronounced in persons with lower intake of nutrients related to arsenic metabolism and cardiovascular health. Future research is needed to evaluate the effect of low-level arsenic exposure on specific cardiovascular outcomes.","Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: A population-based, cross-sectional studyAbs: The authors performed a cross-sectional analysis to evaluate the association between arsenic exposure from drinking water and blood pressure using baseline data of 10,910 participants in the Health Effects of Arsenic Longitudinal Study in Bangladesh (October 2000-May 2002). A time-weighted well arsenic concentration (TWA) based on current and past use of drinking wells was derived. Odds ratios for high pulse pressure (> or = 55 mmHg) by increasing TWA quintiles (< or = 8, 8.1-40.8, 40.9-91.0, 91.1-176.0, and 176.1-864.0 microg/liter) were 1.00 (referent), 1.39 (95% confidence interval (CI): 1.14, 1.71), 1.21 (95% CI: 0.99, 1.49), 1.19 (95% CI: 0.97, 1.45), and 1.19 (95% CI: 0.97, 1.46). Among participants with a lower than average dietary intake level of B vitamins and folate, the odds ratios for high pulse pressure by increasing TWA quintiles were 1.00 (referent), 1.84 (95% CI: 1.07, 3.16), 1.89 (95% CI: 1.11, 3.20), 1.83 (95% CI: 1.09, 3.07), and 1.89 (95% CI: 1.12, 3.20). The odds ratios for systolic hypertension suggest a similar but weaker association. No apparent associations were observed between TWA and general or diastolic hypertension. These findings indicate that the effect of low-level arsenic exposure on blood pressure is nonlinear and may be more pronounced in persons with lower intake of nutrients related to arsenic metabolism and cardiovascular health. Future research is needed to evaluate the effect of low-level arsenic exposure on specific cardiovascular outcomes."
463,Chen et al. 2007,A prospective study of blood selenium levels and the risk of arsenic-related premalignant skin lesions," Arsenic exposure from drinking water is considered to be a risk factor for skin and internal cancers. Animal studies suggest a potential antagonism between arsenic and selenium in the body. We did a case-cohort analysis to prospectively evaluate the association between arsenic-related premalignant skin lesions and prediagnostic blood selenium levels in 303 cases of skin lesions newly diagnosed from November 2002 to April 2004 and 849 subcohort members randomly selected from the 8,092 participants in the Health Effects of Arsenic Longitudinal Study with available baseline blood and urine samples collected in 2000. Incidence rate ratios for skin lesions in increasing blood selenium quintiles were 1.00 (reference), 0.68 [95% confidence interval (95% CI), 0.39-1.18], 0.51 (95% CI, 0.29-0.87), 0.52 (95% CI, 0.30-0.91), and 0.53 (95% CI, 0.31-0.90). Effect estimates remained similar with adjustments for age, sex, body mass index, smoking status, excessive sunlight exposure (in men), well water arsenic concentration at baseline, and nutritional intakes of folate, iron, protein, vitamin E, and B vitamins. At any given arsenic exposure level, the risk of premalignant skin lesions was consistently greater among participants with blood selenium lower than the average level. The findings support the hypothesis that dietary selenium intake may reduce the incidence of arsenic-related premalignant skin lesions among populations exposed to arsenic exposure from drinking water.","A prospective study of blood selenium levels and the risk of arsenic-related premalignant skin lesionsAbs: Arsenic exposure from drinking water is considered to be a risk factor for skin and internal cancers. Animal studies suggest a potential antagonism between arsenic and selenium in the body. We did a case-cohort analysis to prospectively evaluate the association between arsenic-related premalignant skin lesions and prediagnostic blood selenium levels in 303 cases of skin lesions newly diagnosed from November 2002 to April 2004 and 849 subcohort members randomly selected from the 8,092 participants in the Health Effects of Arsenic Longitudinal Study with available baseline blood and urine samples collected in 2000. Incidence rate ratios for skin lesions in increasing blood selenium quintiles were 1.00 (reference), 0.68 [95% confidence interval (95% CI), 0.39-1.18], 0.51 (95% CI, 0.29-0.87), 0.52 (95% CI, 0.30-0.91), and 0.53 (95% CI, 0.31-0.90). Effect estimates remained similar with adjustments for age, sex, body mass index, smoking status, excessive sunlight exposure (in men), well water arsenic concentration at baseline, and nutritional intakes of folate, iron, protein, vitamin E, and B vitamins. At any given arsenic exposure level, the risk of premalignant skin lesions was consistently greater among participants with blood selenium lower than the average level. The findings support the hypothesis that dietary selenium intake may reduce the incidence of arsenic-related premalignant skin lesions among populations exposed to arsenic exposure from drinking water."
464,Chen et al. 1986,"A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan"," A total of 69 bladder cancer, 76 lung cancer and 59 liver cancer deceased cases and 368 alive community controls group-matched on age and sex were studied to evaluate the association between high-arsenic artesian well water and cancers in the endemic area of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous arsenic exposure. According to a standardized structured questionnaire, information on risk factors was obtained through proxy interview of the cases and personal interview of the controls. A positive dose-response relationship was observed between the exposure to artesian well water and cancers of bladder, lung and liver. The age-sex-adjusted odds ratios of developing bladder, lung and liver cancers for those who had used artesian well water for 40 or more years were 3.90, 3.39, and 2.67, respectively, as compared with those who never used artesian well water. Multiple binary logistic regression analyses showed that the dose-response relationships and odds ratios remained much the same while other risk factors were further adjusted.","A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in TaiwanAbs: A total of 69 bladder cancer, 76 lung cancer and 59 liver cancer deceased cases and 368 alive community controls group-matched on age and sex were studied to evaluate the association between high-arsenic artesian well water and cancers in the endemic area of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous arsenic exposure. According to a standardized structured questionnaire, information on risk factors was obtained through proxy interview of the cases and personal interview of the controls. A positive dose-response relationship was observed between the exposure to artesian well water and cancers of bladder, lung and liver. The age-sex-adjusted odds ratios of developing bladder, lung and liver cancers for those who had used artesian well water for 40 or more years were 3.90, 3.39, and 2.67, respectively, as compared with those who never used artesian well water. Multiple binary logistic regression analyses showed that the dose-response relationships and odds ratios remained much the same while other risk factors were further adjusted."
465,Chen et al. 1985,Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers," The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (SMR) and cumulative mortality rate were significantly high in blackfoot disease-endemic areas for cancers of bladder, kidney, skin, lung, liver, and colon. The SMRs for cancers of bladder, kidney, skin, lung, liver, and colon were 1100, 772, 534, 320, 170, and 160, respectively, for males, and 2009, 1119, 652, 413, 229, and 168, respectively, for females. A dose-response relationship was observed between SMRs of the cancers and blackfoot disease prevalence rate of the villages and townships in the endemic areas. SMRs of cancers were greater in villages where only artesian wells were used as the drinking water source than in villages using both artesian and shallow wells, and even greater than in villages using shallow wells only.","Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancersAbs: The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (SMR) and cumulative mortality rate were significantly high in blackfoot disease-endemic areas for cancers of bladder, kidney, skin, lung, liver, and colon. The SMRs for cancers of bladder, kidney, skin, lung, liver, and colon were 1100, 772, 534, 320, 170, and 160, respectively, for males, and 2009, 1119, 652, 413, 229, and 168, respectively, for females. A dose-response relationship was observed between SMRs of the cancers and blackfoot disease prevalence rate of the villages and townships in the endemic areas. SMRs of cancers were greater in villages where only artesian wells were used as the drinking water source than in villages using both artesian and shallow wells, and even greater than in villages using shallow wells only."
466,Chen et al. 2006,Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh," Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies.","Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in BangladeshAbs: Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies."
467,Schmitt et al. 2005,Human nails as a biomarker of arsenic exposure from well water in Inner Mongolia: comparing atomic fluorescence spectrometry and neutron activation analysis," Arsenic (As) is found naturally in the geological strata within the Ba Men Region of Inner Mongolia, China. A study was conducted to compare the total As measurements from two analytical techniques: instrumental neutron activation analysis (INAA) and atomic fluorescence spectrometry (AFS), and to verify nails as an exposure biomarker in this population. In 1999, nail and water samples were collected in a pilot study. Fingernails and toenails were pooled from 32 participants and analysed for total As by both INAA and AFS. Mean nail As values were 14.8+/-2.4 and 19.4+/-2.8 microg g-1 (+/-SEM) for INAA and AFS, respectively. Results from these two methods were significantly correlated (r=0.93, p<0.0001). In 2000, a second study was conducted and INAA was used to measure total As in toenails from 314 Ba Men residents. Well water samples were collected from 121 households and analysed by AFS. A significant correlation was observed between toenail and well water As (r=0.84, p<0.0001). Based on the results, INAA was significantly correlated with AFS and proved to be a reliable measure of nail As levels. In this population, toenail samples are a useful internal As exposure biomarker from drinking water sources.","Human nails as a biomarker of arsenic exposure from well water in Inner Mongolia: comparing atomic fluorescence spectrometry and neutron activation analysisAbs: Arsenic (As) is found naturally in the geological strata within the Ba Men Region of Inner Mongolia, China. A study was conducted to compare the total As measurements from two analytical techniques: instrumental neutron activation analysis (INAA) and atomic fluorescence spectrometry (AFS), and to verify nails as an exposure biomarker in this population. In 1999, nail and water samples were collected in a pilot study. Fingernails and toenails were pooled from 32 participants and analysed for total As by both INAA and AFS. Mean nail As values were 14.8+/-2.4 and 19.4+/-2.8 microg g-1 (+/-SEM) for INAA and AFS, respectively. Results from these two methods were significantly correlated (r=0.93, p<0.0001). In 2000, a second study was conducted and INAA was used to measure total As in toenails from 314 Ba Men residents. Well water samples were collected from 121 households and analysed by AFS. A significant correlation was observed between toenail and well water As (r=0.84, p<0.0001). Based on the results, INAA was significantly correlated with AFS and proved to be a reliable measure of nail As levels. In this population, toenail samples are a useful internal As exposure biomarker from drinking water sources."
468,Schoof et al. 1998,Dietary arsenic intake in Taiwanese districts with elevated arsenic in drinking water," Inorganic arsenic in dietary staples (ie., yams and rice) may have substantially contributed to exposure and adverse health effects observed in an endemic Taiwanese population historically exposed to arsenic in drinking water. Observations of this population were used by the U.S. Environmental Protection Agency to derive toxicity values that form the basis for arsenic risk assessment and various regulations in the United States. However, data were previously insuffcient to accurately estimate dietary intake. Rice and yam samples collected in 1993 and 1995 from Taiwanese districts with endemic arsenic were analyzed for total arsenic and for inorganic and organic monoand dimethylarsenic. The acid digestion techniques used in the analyses are among the best to preserve organic arsenic in the test sample. Furthermore, concurrent analyses of the proportion of inorganic arsenic in split samples of rice and yams collected in the 1995 investigation were in good agreement, despite using a different digestion method. These data support a likely mean dietary intake of 50 ¡.g/day with a range of 15 to 2Il ¡.g/day. Consideration of dietary intake may result in a downward revision of the assumed potency of ingested arsenic as reflected in EPA's toxicity values.","Dietary arsenic intake in Taiwanese districts with elevated arsenic in drinking waterAbs: Inorganic arsenic in dietary staples (ie., yams and rice) may have substantially contributed to exposure and adverse health effects observed in an endemic Taiwanese population historically exposed to arsenic in drinking water. Observations of this population were used by the U.S. Environmental Protection Agency to derive toxicity values that form the basis for arsenic risk assessment and various regulations in the United States. However, data were previously insuffcient to accurately estimate dietary intake. Rice and yam samples collected in 1993 and 1995 from Taiwanese districts with endemic arsenic were analyzed for total arsenic and for inorganic and organic monoand dimethylarsenic. The acid digestion techniques used in the analyses are among the best to preserve organic arsenic in the test sample. Furthermore, concurrent analyses of the proportion of inorganic arsenic in split samples of rice and yams collected in the 1995 investigation were in good agreement, despite using a different digestion method. These data support a likely mean dietary intake of 50 ¡.g/day with a range of 15 to 2Il ¡.g/day. Consideration of dietary intake may result in a downward revision of the assumed potency of ingested arsenic as reflected in EPA's toxicity values."
469,Schoof et al. 1999,A market basket survey of inorganic arsenic in food," Dietary arsenic intake estimates based on surveys of total arsenic concentrations appear to be dominated by intake of the relatively non-toxic, organic arsenic forms found in seafood. Concentrations of inorganic arsenic in food have not been not well characterized. Accurate dietary intake estimates for inorganic arsenic are needed to support studies of arsenic's status as an essential nutrient, and to establish background levels of exposure to inorganic arsenic. In the market basket survey reported here, 40 commodities anticipated to provide at least 90% of dietary inorganic arsenic intake were identified. Four samples of each commodity were collected. Total arsenic was analysed using an NaOH digestion and inductively coupled plasma-mass spectrometry. Separate aliquots were analysed for arsenic species using an HCl digestion and hydride atomic absorption spectroscopy. Consistent with earlier studies, total arsenic concentrations (all concentrations reported as elemental arsenic per tissue wet weight) were highest in the seafoods sampled (ranging from 160 ng/g in freshwater fish to 2360 ng/g in saltwater fish). In contrast, average inorganic arsenic in seafood ranged from less than 1 ng/g to 2 ng/g. The highest inorganic arsenic values were found in raw rice (74 ng/g), followed by flour (11 ng/g), grape juice (9 ng/g) and cooked spinach (6 ng/g). Thus, grains and produce are expected to be significant contributors to dietary inorganic arsenic intake.","A market basket survey of inorganic arsenic in foodAbs: Dietary arsenic intake estimates based on surveys of total arsenic concentrations appear to be dominated by intake of the relatively non-toxic, organic arsenic forms found in seafood. Concentrations of inorganic arsenic in food have not been not well characterized. Accurate dietary intake estimates for inorganic arsenic are needed to support studies of arsenic's status as an essential nutrient, and to establish background levels of exposure to inorganic arsenic. In the market basket survey reported here, 40 commodities anticipated to provide at least 90% of dietary inorganic arsenic intake were identified. Four samples of each commodity were collected. Total arsenic was analysed using an NaOH digestion and inductively coupled plasma-mass spectrometry. Separate aliquots were analysed for arsenic species using an HCl digestion and hydride atomic absorption spectroscopy. Consistent with earlier studies, total arsenic concentrations (all concentrations reported as elemental arsenic per tissue wet weight) were highest in the seafoods sampled (ranging from 160 ng/g in freshwater fish to 2360 ng/g in saltwater fish). In contrast, average inorganic arsenic in seafood ranged from less than 1 ng/g to 2 ng/g. The highest inorganic arsenic values were found in raw rice (74 ng/g), followed by flour (11 ng/g), grape juice (9 ng/g) and cooked spinach (6 ng/g). Thus, grains and produce are expected to be significant contributors to dietary inorganic arsenic intake."
470,Sciandrello et al. 2004,Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells," Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar finding was the preferential involvement of a particular chromosome in dicentric rearrangements observed in some isolated ASO clones. Interestingly, by immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA hypomethylation, induced by arsenic immediately after the acute treatment, was found to affect those ASO clones characterized by aneuploidy and chromosomal rearrangements. These findings demonstrate that short-term exposure to arsenic has long-term effects and suggest that genome-wide DNA hypomethylation enhances genetic instability.","Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cellsAbs: Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar finding was the preferential involvement of a particular chromosome in dicentric rearrangements observed in some isolated ASO clones. Interestingly, by immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA hypomethylation, induced by arsenic immediately after the acute treatment, was found to affect those ASO clones characterized by aneuploidy and chromosomal rearrangements. These findings demonstrate that short-term exposure to arsenic has long-term effects and suggest that genome-wide DNA hypomethylation enhances genetic instability."
471,See et al. 2007,Dose-response relationship between ingested arsenic and cataracts among residents in Southwestern Taiwan," This association study was carried out to examine the effect of long-term exposure to ingested arsenic on various types of cataract. A total of 349 residents living in arseniasis-hyperendemic villages of southwestern Taiwan were recruited. Cumulative arsenic exposure was derived from the history of consuming artesian well water and the arsenic level in well water. The Lens Opacities System III was used to classify different types of cataract. The cataract surgery prevalence was 10% for the age group of 50 or more years. Cortical opacity was most common (35%), while nuclear and posterior subcapsular opacities were observed in 24% and 22% of subjects, respectively. Diabetes mellitus was a significant risk factor for all types of cataract. Occupational sunlight exposure was associated with cortical and posterior subcapsular opacities in a dose-response relationship. The cumulative exposure to arsenic from artesian well water and the duration of consuming artesian well water were associated with an increased risk of all types of lens opacity. But statistically significant dose-response relations with the cumulative arsenic exposure and the duration of consuming artesian well water were observed only for posterior subcapsular opacity (P=0.014 and P=0.023, respectively) after adjustment for age, sex, diabetes status, and occupational sunlight exposure. It was concluded that there was an increasing prevalence of posterior subcapsular opacity with the increase in exposure to ingested arsenic.","Dose-response relationship between ingested arsenic and cataracts among residents in Southwestern TaiwanAbs: This association study was carried out to examine the effect of long-term exposure to ingested arsenic on various types of cataract. A total of 349 residents living in arseniasis-hyperendemic villages of southwestern Taiwan were recruited. Cumulative arsenic exposure was derived from the history of consuming artesian well water and the arsenic level in well water. The Lens Opacities System III was used to classify different types of cataract. The cataract surgery prevalence was 10% for the age group of 50 or more years. Cortical opacity was most common (35%), while nuclear and posterior subcapsular opacities were observed in 24% and 22% of subjects, respectively. Diabetes mellitus was a significant risk factor for all types of cataract. Occupational sunlight exposure was associated with cortical and posterior subcapsular opacities in a dose-response relationship. The cumulative exposure to arsenic from artesian well water and the duration of consuming artesian well water were associated with an increased risk of all types of lens opacity. But statistically significant dose-response relations with the cumulative arsenic exposure and the duration of consuming artesian well water were observed only for posterior subcapsular opacity (P=0.014 and P=0.023, respectively) after adjustment for age, sex, diabetes status, and occupational sunlight exposure. It was concluded that there was an increasing prevalence of posterior subcapsular opacity with the increase in exposure to ingested arsenic."
472,Chen et al. 2003,Arsenic methylation and skin cancer risk in southwestern Taiwan," Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.","Arsenic methylation and skin cancer risk in southwestern TaiwanAbs: Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women."
473,Chen et al. 2004,"Ingested arsenic, cigarette smoking, and lung cancer risk: A follow-up study in arseniasis-endemic areas in Taiwan"," CONTEXT: Arsenic has been documented as a lung carcinogen in humans in only a few follow-up studies, which were limited by a small number of cases or the lack of information on cigarette smoking. OBJECTIVES: To elucidate the dose-response relationship between ingested arsenic and lung cancer and to assess the effect of cigarette smoking on the arsenic-lung cancer association. DESIGN, SETTING, AND PARTICIPANTS: A total of 2503 residents in southwestern and 8088 in northeastern arseniasis-endemic areas in Taiwan were followed up for an average period of 8 years. Information on arsenic exposure, cigarette smoking, and other risk factors was collected at enrollment through standardized questionnaire interview. MAIN OUTCOME MEASURES: The incidence of lung cancer was ascertained through linkage with national cancer registry profiles in Taiwan (January 1985-December 2000). The joint effect of arsenic and cigarette smoking was estimated by both etiologic fraction and synergy index. RESULTS: There were 139 newly diagnosed lung cancer cases during a follow-up period of 83,783 person-years. After adjustment for cigarette smoking and other risk factors, there was a monotonic trend of lung cancer risk by arsenic level in drinking water of less than 10 to 700 microg/L or more (P<.001). The relative risk was 3.29 (95% confidence interval, 1.60-6.78) for the highest arsenic level compared with the lowest. The etiologic fraction of lung cancer attributable to the joint exposure of ingested arsenic and cigarette smoking ranged from 32% to 55%. The synergy indices ranged from 1.62 to 2.52, indicating a synergistic effect of ingested arsenic and cigarette smoking on lung cancer. CONCLUSIONS: There was a significant dose-response trend of ingested arsenic on lung cancer risk, which was more prominent among cigarette smokers. The risk assessment of lung cancer induced by ingested arsenic should take cigarette smoking into consideration.","Ingested arsenic, cigarette smoking, and lung cancer risk: A follow-up study in arseniasis-endemic areas in TaiwanAbs: CONTEXT: Arsenic has been documented as a lung carcinogen in humans in only a few follow-up studies, which were limited by a small number of cases or the lack of information on cigarette smoking. OBJECTIVES: To elucidate the dose-response relationship between ingested arsenic and lung cancer and to assess the effect of cigarette smoking on the arsenic-lung cancer association. DESIGN, SETTING, AND PARTICIPANTS: A total of 2503 residents in southwestern and 8088 in northeastern arseniasis-endemic areas in Taiwan were followed up for an average period of 8 years. Information on arsenic exposure, cigarette smoking, and other risk factors was collected at enrollment through standardized questionnaire interview. MAIN OUTCOME MEASURES: The incidence of lung cancer was ascertained through linkage with national cancer registry profiles in Taiwan (January 1985-December 2000). The joint effect of arsenic and cigarette smoking was estimated by both etiologic fraction and synergy index. RESULTS: There were 139 newly diagnosed lung cancer cases during a follow-up period of 83,783 person-years. After adjustment for cigarette smoking and other risk factors, there was a monotonic trend of lung cancer risk by arsenic level in drinking water of less than 10 to 700 microg/L or more (P<.001). The relative risk was 3.29 (95% confidence interval, 1.60-6.78) for the highest arsenic level compared with the lowest. The etiologic fraction of lung cancer attributable to the joint exposure of ingested arsenic and cigarette smoking ranged from 32% to 55%. The synergy indices ranged from 1.62 to 2.52, indicating a synergistic effect of ingested arsenic and cigarette smoking on lung cancer. CONCLUSIONS: There was a significant dose-response trend of ingested arsenic on lung cancer risk, which was more prominent among cigarette smokers. The risk assessment of lung cancer induced by ingested arsenic should take cigarette smoking into consideration."
474,Otto et al. 2007,Neurosensory effects of chronic human exposure to arsenic associated with body burden and environmental measures," Exposure to arsenic in drinking water is known to produce a variety of health problems, including peripheral neuropathy. Auditory, visual and somatosensory impairment have been reported in Mongolian farmers living in the Yellow River Valley, where drinking water is contaminated by arsenic. In the present study, sensory tests, including pinprick and vibration thresholds, were administered to 320 residents with well-water arsenic levels, ranging from non-detectable to 690 microg/L. Vibration thresholds in the second and fifth fingers of both hands were measured using a vibrothesiometer. Drinking water, urine and toenail samples were obtained to assess arsenic exposure and body burden. Regression analyses indicated significant associations of pinprick scores and vibration thresholds with all arsenic measures. Vibration thresholds were more strongly associated with urinary than water or nail arsenic measures, but odds ratios for decreased pinprick sensitivity were highest for the water arsenic measure. Results of the current study indicate neurosensory effects of arsenic exposure at concentrations well below the 1000 microg/L drinking water level specified by NRC, and suggest that non-carcinogenic end-points, such as vibration thresholds, are useful in the risk assessment of exposure to arsenic in drinking water.","Neurosensory effects of chronic human exposure to arsenic associated with body burden and environmental measuresAbs: Exposure to arsenic in drinking water is known to produce a variety of health problems, including peripheral neuropathy. Auditory, visual and somatosensory impairment have been reported in Mongolian farmers living in the Yellow River Valley, where drinking water is contaminated by arsenic. In the present study, sensory tests, including pinprick and vibration thresholds, were administered to 320 residents with well-water arsenic levels, ranging from non-detectable to 690 microg/L. Vibration thresholds in the second and fifth fingers of both hands were measured using a vibrothesiometer. Drinking water, urine and toenail samples were obtained to assess arsenic exposure and body burden. Regression analyses indicated significant associations of pinprick scores and vibration thresholds with all arsenic measures. Vibration thresholds were more strongly associated with urinary than water or nail arsenic measures, but odds ratios for decreased pinprick sensitivity were highest for the water arsenic measure. Results of the current study indicate neurosensory effects of arsenic exposure at concentrations well below the 1000 microg/L drinking water level specified by NRC, and suggest that non-carcinogenic end-points, such as vibration thresholds, are useful in the risk assessment of exposure to arsenic in drinking water."
475,Otto et al. 2006,Neurosensory effects of chronic exposure to arsenic via drinking water in Inner Mongolia: II. Vibrotactile and visual function," This study was designed to assess the effects of exposure to arsenic in drinking water on visual and vibrotactile function in residents of the Bamen region of Inner Mongolia, China. Arsenic was measured by hydride generation atomic fluorescence. 321 participants were divided into three exposure groups- low (non-detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking water (AsW). Three visual tests were administered: acuity, contrast sensitivity and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration thresholds were measured with a vibrothesiometer. Vibration thresholds were significantly elevated in the high exposure group compared to other groups. Further analysis using a spline regression model suggested that the threshold for vibratory effects is between 150-170 microg/l AsW. These findings provide the first evidence that chronic exposure to arsenic in drinking water impairs vibrotactile thresholds. The results also indicate that arsenic affects neurological function well below the 1000 microg/I concentration reported by NRC (1999). No evidence of arsenic-related effects on visual function was found.","Neurosensory effects of chronic exposure to arsenic via drinking water in Inner Mongolia: II. Vibrotactile and visual functionAbs: This study was designed to assess the effects of exposure to arsenic in drinking water on visual and vibrotactile function in residents of the Bamen region of Inner Mongolia, China. Arsenic was measured by hydride generation atomic fluorescence. 321 participants were divided into three exposure groups- low (non-detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking water (AsW). Three visual tests were administered: acuity, contrast sensitivity and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration thresholds were measured with a vibrothesiometer. Vibration thresholds were significantly elevated in the high exposure group compared to other groups. Further analysis using a spline regression model suggested that the threshold for vibratory effects is between 150-170 microg/l AsW. These findings provide the first evidence that chronic exposure to arsenic in drinking water impairs vibrotactile thresholds. The results also indicate that arsenic affects neurological function well below the 1000 microg/I concentration reported by NRC (1999). No evidence of arsenic-related effects on visual function was found."
476,Chen et al. 2010,Arsenic in drinking water and risk of urinary tract cancer: A follow-up study from northeastern Taiwan,"<div>&nbsp;The evidence linking arsenic in drinking water with increased urinary cancer risk comes from populations in relatively high exposure areas (&gt;100 microg/L), whereas studies from lower exposure areas (&lt;100 microg/L) reported inconsistent results. A previous study conducted in northeastern Taiwan, where residents were exposed to relatively lower concentrations, reported increased risk of urinary cancer in a dose-response way. Using the same cohort with longer follow-up, we conducted analysis to elucidate the relationship between ingested arsenic and urinary cancer in lower exposure groups and assessed the influence of duration, recency, and latency of drinking arsenic-containing well water. A total of 8,086 residents from northeastern Taiwan were followed for 12 years. Incident urinary cancer was ascertained through linkage with the national cancer registry. All analysis was done by Cox proportional hazards regression models. There were 45 incidences of urinary cancer and a monotonic increased risk of urinary cancer was found with increasing arsenic concentration (P &lt; 0.001). For the highly exposed (&gt;100 microg/L), the relative risks (RR) were &gt;5-fold, whereas the risk was elevated but not significant for low exposure (&lt;100 microg/L). Relative to the arsenic concentration &lt;10 microg/L, those who drank well water with higher concentration from birth [RR, 3.69; 95% confidence interval (95% CI), 1.31-10.4], still drank at enrollment (RR, 3.50; 95% CI, 1.33-9.22), and drank for &gt;50 years (RR, 4.12; 95% CI, 1.48-11.5) has a signigicantly increased risk of urinary cancer. &nbsp;When restricted to urothelial carcinoma, all risk estimates including concentration and characteristics of well water consumption were higher. </div>","Arsenic in drinking water and risk of urinary tract cancer: A follow-up study from northeastern TaiwanAbs:<div>&nbsp;The evidence linking arsenic in drinking water with increased urinary cancer risk comes from populations in relatively high exposure areas (&gt;100 microg/L), whereas studies from lower exposure areas (&lt;100 microg/L) reported inconsistent results. A previous study conducted in northeastern Taiwan, where residents were exposed to relatively lower concentrations, reported increased risk of urinary cancer in a dose-response way. Using the same cohort with longer follow-up, we conducted analysis to elucidate the relationship between ingested arsenic and urinary cancer in lower exposure groups and assessed the influence of duration, recency, and latency of drinking arsenic-containing well water. A total of 8,086 residents from northeastern Taiwan were followed for 12 years. Incident urinary cancer was ascertained through linkage with the national cancer registry. All analysis was done by Cox proportional hazards regression models. There were 45 incidences of urinary cancer and a monotonic increased risk of urinary cancer was found with increasing arsenic concentration (P &lt; 0.001). For the highly exposed (&gt;100 microg/L), the relative risks (RR) were &gt;5-fold, whereas the risk was elevated but not significant for low exposure (&lt;100 microg/L). Relative to the arsenic concentration &lt;10 microg/L, those who drank well water with higher concentration from birth [RR, 3.69; 95% confidence interval (95% CI), 1.31-10.4], still drank at enrollment (RR, 3.50; 95% CI, 1.33-9.22), and drank for &gt;50 years (RR, 4.12; 95% CI, 1.48-11.5) has a signigicantly increased risk of urinary cancer. &nbsp;When restricted to urothelial carcinoma, all risk estimates including concentration and characteristics of well water consumption were higher. </div>"
477,Shen et al. 2006,Elevation of cellular BPDE uptake by human cells: a possible factor contributing to co-carcinogenicity by arsenite," BACKGROUND: Arsenite (iAsIII) can promote mutagenicity and carcinogenicity of other carcinogens. Considerable attention has focused on interference with DNA repair by inorganic arsenic, especially the nucleotide excision repair (NER) pathway, whereas less is known about the effect of arsenic on the induction of DNA damage by other agents. OBJECTIVES: We examined how arsenic modulates DNA damage by other chemicals. METHODS: We used an NER-deficient cell line to dissect DNA damage induction from DNA repair and to examine the effects of iAsIII on the formation of benzo[a]pyrene diol epoxide (BPDE)-DNA adducts. RESULTS: We found that pretreatment with iAsIII at subtoxic concentrations (10 microM) led to enhanced formation of BPDE-DNA adducts. Reduced glutathione levels, glutathione S-transferase activity and chromatin accessibility were also measured after iAsIII treatment, but none of these factors appeared to account for the enhanced formation of DNA adducts. However, we found that pretreatment with iAsIII increased the cellular uptake of BPDE in a dose-dependent manner. CONCLUSIONS: Our results suggest that iAsIII enhanced the formation of BPDE-DNA adducts by increasing the cellular uptake of BPDE. Therefore, the ability of arsenic to increase the bioavailability of other carcinogens may contribute to arsenic co-carcinogenicity.","Elevation of cellular BPDE uptake by human cells: a possible factor contributing to co-carcinogenicity by arseniteAbs: BACKGROUND: Arsenite (iAsIII) can promote mutagenicity and carcinogenicity of other carcinogens. Considerable attention has focused on interference with DNA repair by inorganic arsenic, especially the nucleotide excision repair (NER) pathway, whereas less is known about the effect of arsenic on the induction of DNA damage by other agents. OBJECTIVES: We examined how arsenic modulates DNA damage by other chemicals. METHODS: We used an NER-deficient cell line to dissect DNA damage induction from DNA repair and to examine the effects of iAsIII on the formation of benzo[a]pyrene diol epoxide (BPDE)-DNA adducts. RESULTS: We found that pretreatment with iAsIII at subtoxic concentrations (10 microM) led to enhanced formation of BPDE-DNA adducts. Reduced glutathione levels, glutathione S-transferase activity and chromatin accessibility were also measured after iAsIII treatment, but none of these factors appeared to account for the enhanced formation of DNA adducts. However, we found that pretreatment with iAsIII increased the cellular uptake of BPDE in a dose-dependent manner. CONCLUSIONS: Our results suggest that iAsIII enhanced the formation of BPDE-DNA adducts by increasing the cellular uptake of BPDE. Therefore, the ability of arsenic to increase the bioavailability of other carcinogens may contribute to arsenic co-carcinogenicity."
478,Chen et al. 2006,"Modification of risk of arsenic-induced skin lesions by sunlight exposure, smoking, and occupational exposures in Bangladesh"," BACKGROUND: The risk of skin lesions associated with arsenic exposure from drinking water in Bangladesh is considerably greater in men than in women. METHODS: Using baseline data from 11,062 cohort members in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, we performed a cross-sectional analysis to evaluate whether the association between arsenic exposure from drinking water and the risk of skin lesions is modified by tobacco smoking, excessive sunlight, the use of fertilizer, and the use of pesticides. A time-weighted well arsenic concentration was estimated for each participant by incorporating history of well use. Relative excess risk for interaction (RERI) and its 95% confidence intervals (CIs) were estimated using adjusted prevalence odds ratios. RESULTS: We observed a synergistic effect between the highest level of arsenic exposure (> 113 microg/L) and tobacco smoking on risk of skin lesions in men (RERI = 1.5 [95% CI = 0.3 to 2.7] overall and 1.7 [0.2 to 3.4] for the subpopulation with longer-term arsenic exposure). We also observed suggestive synergistic effects between higher levels (28.1-113.0 microg/L and 113.1-864.0 microg/L) of arsenic exposure and fertilizer use in men (RERI = 1.0 [-0.2 to 2.2] and 1.3 [-0.2 to 2.9] respectively). Furthermore, the risk of skin lesions associated with any given level of arsenic exposure was greater in men with excessive sun exposure. The patterns of effect estimates in women indicate similar-but-weaker interaction effects of arsenic exposure with tobacco smoking and fertilizer use. CONCLUSIONS: These findings help explain why the risk of arsenic-related skin lesions was much greater in men than in women in Bangladesh. Because most arsenic-induced skin cancers arise from these skin lesions, treatment and remediation plans should take into consideration these etiologic cofactors.","Modification of risk of arsenic-induced skin lesions by sunlight exposure, smoking, and occupational exposures in BangladeshAbs: BACKGROUND: The risk of skin lesions associated with arsenic exposure from drinking water in Bangladesh is considerably greater in men than in women. METHODS: Using baseline data from 11,062 cohort members in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, we performed a cross-sectional analysis to evaluate whether the association between arsenic exposure from drinking water and the risk of skin lesions is modified by tobacco smoking, excessive sunlight, the use of fertilizer, and the use of pesticides. A time-weighted well arsenic concentration was estimated for each participant by incorporating history of well use. Relative excess risk for interaction (RERI) and its 95% confidence intervals (CIs) were estimated using adjusted prevalence odds ratios. RESULTS: We observed a synergistic effect between the highest level of arsenic exposure (> 113 microg/L) and tobacco smoking on risk of skin lesions in men (RERI = 1.5 [95% CI = 0.3 to 2.7] overall and 1.7 [0.2 to 3.4] for the subpopulation with longer-term arsenic exposure). We also observed suggestive synergistic effects between higher levels (28.1-113.0 microg/L and 113.1-864.0 microg/L) of arsenic exposure and fertilizer use in men (RERI = 1.0 [-0.2 to 2.2] and 1.3 [-0.2 to 2.9] respectively). Furthermore, the risk of skin lesions associated with any given level of arsenic exposure was greater in men with excessive sun exposure. The patterns of effect estimates in women indicate similar-but-weaker interaction effects of arsenic exposure with tobacco smoking and fertilizer use. CONCLUSIONS: These findings help explain why the risk of arsenic-related skin lesions was much greater in men than in women in Bangladesh. Because most arsenic-induced skin cancers arise from these skin lesions, treatment and remediation plans should take into consideration these etiologic cofactors."
479,Chen et al. 2007,Association between arsenic exposure from drinking water and plasma levels of soluble cell adhesion molecules," BACKGROUND: Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority. OBJECTIVE: We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh. METHODS: The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 x 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up. RESULTS: Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-mug/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00-0.20] and 0.33 ng/mL (95% CI, 0.15-0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-microg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01-0.22) and 0.17 ng/mL (95% CI, 0.00-0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period. CONCLUSIONS: The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.","Association between arsenic exposure from drinking water and plasma levels of soluble cell adhesion moleculesAbs: BACKGROUND: Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority. OBJECTIVE: We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh. METHODS: The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 x 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up. RESULTS: Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-mug/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00-0.20] and 0.33 ng/mL (95% CI, 0.15-0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-microg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01-0.22) and 0.17 ng/mL (95% CI, 0.00-0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period. CONCLUSIONS: The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease."
480,Chen and Gibb 2003,Procedures for calculating cessation lag," Environmental regulations aimed at reducing cancer risks usually have the effect of reducing exposure to a carcinogen at the time the regulation is implemented. The reduction of cancer risk may occur shortly after the reduced exposure or after a considerable period of time. The time of risk reduction associated with exposure reduction will vary by compound. Some recommended measures of the economic benefits associated with environmental regulations are sensitive to the timing of the risk reductions and cannot be effectively addressed by the conventional dose-response procedures. This paper introduces the concept and methodologies for calculating cessation lag effects, with the specific goal of answering the following questions: (1) How many cancer cases are avoided at age t after cessation (or reduction) of exposure concentration? and (2) How long does the effect of an exposure last after exposure has terminated (or been reduced)? The proposed procedures do not require more information than what is required by the conventional dose-response procedures for which cumulative or an averaged lifetime exposure is used.","Procedures for calculating cessation lagAbs: Environmental regulations aimed at reducing cancer risks usually have the effect of reducing exposure to a carcinogen at the time the regulation is implemented. The reduction of cancer risk may occur shortly after the reduced exposure or after a considerable period of time. The time of risk reduction associated with exposure reduction will vary by compound. Some recommended measures of the economic benefits associated with environmental regulations are sensitive to the timing of the risk reductions and cannot be effectively addressed by the conventional dose-response procedures. This paper introduces the concept and methodologies for calculating cessation lag effects, with the specific goal of answering the following questions: (1) How many cancer cases are avoided at age t after cessation (or reduction) of exposure concentration? and (2) How long does the effect of an exposure last after exposure has terminated (or been reduced)? The proposed procedures do not require more information than what is required by the conventional dose-response procedures for which cumulative or an averaged lifetime exposure is used."
481,Chen et al. 1988,Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease," The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.","Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot diseaseAbs: The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area."
482,Meliker et al. 2010,"Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USA"," OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure.","Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USAAbs: OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure."
483,Meza et al. 2007,Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?," The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report.","Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?Abs: The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report."
484,Meza et al. 2005,Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children," We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials.","Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in childrenAbs: We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials."
485,Simeonova et al. 2003,Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice," Epidemiologic studies have shown an association between elevated arsenic levels in drinking water and an increased risk of atherosclerosis and vascular diseases. The studies presented here were performed to evaluate the atherogenic potential of arsenic using a well-established and controlled animal model of human atherosclerosis, mice deficient in apolipoprotein E (ApoE), and in vitro systems including primary human vascular cells. Wild-type and ApoE-deficient mice were exposed to 20 or 100 microg/mL sodium arsenite in drinking water for 24 weeks. As assessed morphometrically, the size of grossly discernible lesions covering the intimal area of aorta were increased significantly in arsenic-treated ApoE-deficient mice compared with nontreated transgenic mice. This effect was not associated with increased levels of serum cholesterol but was accompanied by an accumulation of arsenic in the vessel wall. Introduction of cocoa butter into the diet for 2 weeks resulted in higher serum cholesterol levels and only slight increases in the lesion size in control or arsenic-exposed ApoE-deficient mice. There were no lesions observed in the wild-type C57BL6 mice, resistant to atherosclerosis, whether they received arsenic or control drinking water. In vitro studies, including primary aorta endothelial or smooth muscle cells, were conducted to evaluate whether arsenic induces cellular mechanisms relevant to atherogenesis such as endothelial dysfunction, lipid oxidation, and smooth muscle cell proliferation. Arsenic treatment does not modulate endothelial cell-mediated lipid oxidation or smooth muscle cell proliferation but induced the expression of genes coding inflammatory mediators, including interleukin-8. Induction of endothelial inflammatory activity may play a role in arsenic-related vascular effects.","Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) miceAbs: Epidemiologic studies have shown an association between elevated arsenic levels in drinking water and an increased risk of atherosclerosis and vascular diseases. The studies presented here were performed to evaluate the atherogenic potential of arsenic using a well-established and controlled animal model of human atherosclerosis, mice deficient in apolipoprotein E (ApoE), and in vitro systems including primary human vascular cells. Wild-type and ApoE-deficient mice were exposed to 20 or 100 microg/mL sodium arsenite in drinking water for 24 weeks. As assessed morphometrically, the size of grossly discernible lesions covering the intimal area of aorta were increased significantly in arsenic-treated ApoE-deficient mice compared with nontreated transgenic mice. This effect was not associated with increased levels of serum cholesterol but was accompanied by an accumulation of arsenic in the vessel wall. Introduction of cocoa butter into the diet for 2 weeks resulted in higher serum cholesterol levels and only slight increases in the lesion size in control or arsenic-exposed ApoE-deficient mice. There were no lesions observed in the wild-type C57BL6 mice, resistant to atherosclerosis, whether they received arsenic or control drinking water. In vitro studies, including primary aorta endothelial or smooth muscle cells, were conducted to evaluate whether arsenic induces cellular mechanisms relevant to atherogenesis such as endothelial dysfunction, lipid oxidation, and smooth muscle cell proliferation. Arsenic treatment does not modulate endothelial cell-mediated lipid oxidation or smooth muscle cell proliferation but induced the expression of genes coding inflammatory mediators, including interleukin-8. Induction of endothelial inflammatory activity may play a role in arsenic-related vascular effects."
486,Milton et al. 2005,Chronic arsenic exposure and adverse pregnancy outcomes in Bangladesh," BACKGROUND: Chronic exposure to arsenic through drinking water has the potential to cause adverse pregnancy outcomes, although the association has not been demonstrated conclusively. This cross-sectional study assessed the association between arsenic in drinking water and spontaneous abortion, stillbirth, and neonatal death. METHODS: In this cross-sectional study, 533 women were interviewed. Information on sociodemographic characteristics, drinking water use, and adverse pregnancy outcomes was obtained through a structured pretested interviewer-administered questionnaire. The respondents reported use of a total of 223 tube wells; for 208 wells, water samples were measured using an ultraviolet/visible spectrophotometry method, whereas 15 were measured by flow-injection hydride generation atomic absorption spectrometry (FIHG-AAS). RESULTS: Excess risks for spontaneous abortion and stillbirth were observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for participant's height, history of hypertension and diabetes, and (for neonatal death only) age at first pregnancy. Comparing exposure to arsenic concentration of greater than 50 microg/L with 50 microg/L or less, the odds ratios were 2.5 (95% confidence interval=1.5-4.3) for spontaneous abortion, 2.5 (1.3-4.9) for stillbirth, and 1.8 (0.9-3.6) for neonatal death. CONCLUSIONS: These study findings suggest that chronic arsenic exposure may increase the risk of fetal and infant death.","Chronic arsenic exposure and adverse pregnancy outcomes in BangladeshAbs: BACKGROUND: Chronic exposure to arsenic through drinking water has the potential to cause adverse pregnancy outcomes, although the association has not been demonstrated conclusively. This cross-sectional study assessed the association between arsenic in drinking water and spontaneous abortion, stillbirth, and neonatal death. METHODS: In this cross-sectional study, 533 women were interviewed. Information on sociodemographic characteristics, drinking water use, and adverse pregnancy outcomes was obtained through a structured pretested interviewer-administered questionnaire. The respondents reported use of a total of 223 tube wells; for 208 wells, water samples were measured using an ultraviolet/visible spectrophotometry method, whereas 15 were measured by flow-injection hydride generation atomic absorption spectrometry (FIHG-AAS). RESULTS: Excess risks for spontaneous abortion and stillbirth were observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for participant's height, history of hypertension and diabetes, and (for neonatal death only) age at first pregnancy. Comparing exposure to arsenic concentration of greater than 50 microg/L with 50 microg/L or less, the odds ratios were 2.5 (95% confidence interval=1.5-4.3) for spontaneous abortion, 2.5 (1.3-4.9) for stillbirth, and 1.8 (0.9-3.6) for neonatal death. CONCLUSIONS: These study findings suggest that chronic arsenic exposure may increase the risk of fetal and infant death."
487,Milton et al. 2003,Chronic arsenic exposure and adverse pregnancy outcomes in Bangladesh," Introduction:Chronic arsenic exposure through drinking water has the potential to cause adverse pregnancy outcomes, though the association is not conclusive. This cross sectional study was carried out in two three arsenic affected districts of Bangladesh to determine the association between chronic arsenic exposure through drinking water and spontaneous abortion, stillbirth and neonatal death. Methods:In this cross-sectional study, 533 married, non-smoking females of reproductive age (range 15 to 49 years) with a history of at least one pregnancy, who had been living in the study area since their marriage and drank water from the respective tube well prior to and during the pregnancy were interviewed. Information on sociodemographics, drinking water use, occupation and adverse pregnancy outcomes were obtained through a structured pretested interviewer-administered questionnaire. Out of 2138 tube wells, 203198 water samples were measured using UV/Visible spectrophotometry method while 15 were measured by flow-injection hydride generation atomic absorption spectrometry (FIHG-AAS). Results: A total of 533 female participated in this study. Their mean age was 31.22 years (standard deviation (SD) = 6.44) and the average duration of arsenic exposure of the participants was 8.11 years (SD = 7.32), median duration of exposure was 7 years. Out of the study subjects, 257 (48%) of the study participants did not receive any formal education. The majority of them (51%) got married before the age of 16-years. The mean number of pregnancies was 3.72 (SD = 1.79) and mean number of live births was 3.48 (SD = 1.65). Melanosis was observed among 51 (10%) and keratosis was observed among 43 (8%) participants. The mean and median arsenic concentration of the tube well drinking water of the study participants was 279(SD = 355) ug/L and 116 ppbug/L respectively, ranging from non-detectable level to 1710 ppbug/L . 356 (67%) participants were exposed to arsenic at more than 50 ppbug/L, the recommended level of arsenic in drinking water for Bangladesh. Overall incidence of spontaneous abortion, stillbirth and neonatal death in this study were found as 59.61/1000 live birth, 35.55/1000 live birth and 49.31/1000 live birth respectively. Excess risks for spontaneous abortion, stillbirth and neonatal death were observed among the participants exposed to increasing concentrations of arsenic in drinking water, after adjusting for participant's education, age at marriage, antenatal care and parity. The odds ratio (OR) for spontaneous abortion, stillbirth and neonatal death was 1.93 (95% Confidence Interval [CI]: 1, 11, 3.37), 1.82 (95% CI: 0.94, 3.51) and 1.89 (95% CI: 1.02, 3.53) respectively for females drinking water with 50 ppbug/L compared to 50 ppbug/L arsenic concentration. These risks are both clinically and statistically significant except stillbirth. There was, however, a statistically significant dose-response association between increasing arsenic concentration and stillbirth (p = 0.02), neonatal death (p = 0.01).","Chronic arsenic exposure and adverse pregnancy outcomes in BangladeshAbs: Introduction:Chronic arsenic exposure through drinking water has the potential to cause adverse pregnancy outcomes, though the association is not conclusive. This cross sectional study was carried out in two three arsenic affected districts of Bangladesh to determine the association between chronic arsenic exposure through drinking water and spontaneous abortion, stillbirth and neonatal death. Methods:In this cross-sectional study, 533 married, non-smoking females of reproductive age (range 15 to 49 years) with a history of at least one pregnancy, who had been living in the study area since their marriage and drank water from the respective tube well prior to and during the pregnancy were interviewed. Information on sociodemographics, drinking water use, occupation and adverse pregnancy outcomes were obtained through a structured pretested interviewer-administered questionnaire. Out of 2138 tube wells, 203198 water samples were measured using UV/Visible spectrophotometry method while 15 were measured by flow-injection hydride generation atomic absorption spectrometry (FIHG-AAS). Results: A total of 533 female participated in this study. Their mean age was 31.22 years (standard deviation (SD) = 6.44) and the average duration of arsenic exposure of the participants was 8.11 years (SD = 7.32), median duration of exposure was 7 years. Out of the study subjects, 257 (48%) of the study participants did not receive any formal education. The majority of them (51%) got married before the age of 16-years. The mean number of pregnancies was 3.72 (SD = 1.79) and mean number of live births was 3.48 (SD = 1.65). Melanosis was observed among 51 (10%) and keratosis was observed among 43 (8%) participants. The mean and median arsenic concentration of the tube well drinking water of the study participants was 279(SD = 355) ug/L and 116 ppbug/L respectively, ranging from non-detectable level to 1710 ppbug/L . 356 (67%) participants were exposed to arsenic at more than 50 ppbug/L, the recommended level of arsenic in drinking water for Bangladesh. Overall incidence of spontaneous abortion, stillbirth and neonatal death in this study were found as 59.61/1000 live birth, 35.55/1000 live birth and 49.31/1000 live birth respectively. Excess risks for spontaneous abortion, stillbirth and neonatal death were observed among the participants exposed to increasing concentrations of arsenic in drinking water, after adjusting for participant's education, age at marriage, antenatal care and parity. The odds ratio (OR) for spontaneous abortion, stillbirth and neonatal death was 1.93 (95% Confidence Interval [CI]: 1, 11, 3.37), 1.82 (95% CI: 0.94, 3.51) and 1.89 (95% CI: 1.02, 3.53) respectively for females drinking water with 50 ppbug/L compared to 50 ppbug/L arsenic concentration. These risks are both clinically and statistically significant except stillbirth. There was, however, a statistically significant dose-response association between increasing arsenic concentration and stillbirth (p = 0.02), neonatal death (p = 0.01)."
488,Mitra et al. 2004,"Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, India"," There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.","Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, IndiaAbs: There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic."
489,Singh et al. 2008,Genotoxic effects of arsenic: prevention by functional food-jaggery," Arsenic contamination in groundwater is global human health hazard. There is no effective remedial action of chronic arsenicosis, however, a well-nourished diet can modulate the onset of adverse health effects and the delayed effect of arsenic in drinking water. In the present work, genotoxic effects induced by arsenic through parenteral administration and ameliorate by jaggery. Chromosomal aberrations were more pronounced in arsenic treated mice, while supplementation of jaggery with arsenic reduced the incidence of the aberrations. The outcome of study showed that Jaggery the natural functional food has the efficiency to encounter the genotoxic effects induced by arsenic.","Genotoxic effects of arsenic: prevention by functional food-jaggeryAbs: Arsenic contamination in groundwater is global human health hazard. There is no effective remedial action of chronic arsenicosis, however, a well-nourished diet can modulate the onset of adverse health effects and the delayed effect of arsenic in drinking water. In the present work, genotoxic effects induced by arsenic through parenteral administration and ameliorate by jaggery. Chromosomal aberrations were more pronounced in arsenic treated mice, while supplementation of jaggery with arsenic reduced the incidence of the aberrations. The outcome of study showed that Jaggery the natural functional food has the efficiency to encounter the genotoxic effects induced by arsenic."
490,Miyazaki et al. 2005,The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in mice," Although toxicological and metabolic interactions of arsenic (As) and selenium (Se) have been suggested by epidemiolgical literatures, the past experimental studies mostly focused on acute, high-dose interaction, leaving the long-term, low-dose interaction unexplored. In the present study pregnant mice, fed either Se-deficient or adequate (0 or 5 micromol Se/kg diet, respectively) diet, were given oral gavage of sodium arsenite (0 or 58 micromol/kg per day; chosen as less than half of the fetotoxic dose in this protocol) from gestational day (GD) 7-16. The levels of As and Se as well as five selenoenzymes (glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and type-I, -II and -III iodothyronine deiodinases (DI-I, -II and -III) were examined on GD17 in the tissues of dams and of fetus. The Se-deficient mice showed significantly enhanced accumulation of As compared to the Se-adequate mice in maternal liver (increased by 48%) and fetal brain (by 31%). Although no direct evidence of the enhanced toxicity in the Se-deficient group was obtained, the As exposure affected the levels of Se and selenoenzymes, an effect which was more discernible in Se-deficient group. Although most of theses changes were mild or moderate, the DI-II activity in Se-deficient fetal brain showed a drastic four-fold increase by As exposure, suggesting a possible disturbance of thyroid hormone environment in the fetus. These data suggested that apparently non-toxic, in utero dose of As, showed enhanced accumulation when combined with Se-deficiency and could affect the metabolism/kinetics of Se in fetal brain, which might result in developmental toxicity in mice.","The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in miceAbs: Although toxicological and metabolic interactions of arsenic (As) and selenium (Se) have been suggested by epidemiolgical literatures, the past experimental studies mostly focused on acute, high-dose interaction, leaving the long-term, low-dose interaction unexplored. In the present study pregnant mice, fed either Se-deficient or adequate (0 or 5 micromol Se/kg diet, respectively) diet, were given oral gavage of sodium arsenite (0 or 58 micromol/kg per day; chosen as less than half of the fetotoxic dose in this protocol) from gestational day (GD) 7-16. The levels of As and Se as well as five selenoenzymes (glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and type-I, -II and -III iodothyronine deiodinases (DI-I, -II and -III) were examined on GD17 in the tissues of dams and of fetus. The Se-deficient mice showed significantly enhanced accumulation of As compared to the Se-adequate mice in maternal liver (increased by 48%) and fetal brain (by 31%). Although no direct evidence of the enhanced toxicity in the Se-deficient group was obtained, the As exposure affected the levels of Se and selenoenzymes, an effect which was more discernible in Se-deficient group. Although most of theses changes were mild or moderate, the DI-II activity in Se-deficient fetal brain showed a drastic four-fold increase by As exposure, suggesting a possible disturbance of thyroid hormone environment in the fetus. These data suggested that apparently non-toxic, in utero dose of As, showed enhanced accumulation when combined with Se-deficiency and could affect the metabolism/kinetics of Se in fetal brain, which might result in developmental toxicity in mice."
491,Sinha et al. 2005,Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea," The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.","Arsenic-induced micronuclei formation in mammalian cells and its counteraction by teaAbs: The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic."
492,Slotnick et al. 2007,Toenails as a biomarker of inorganic arsenic intake from drinking water and foods," Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure.","Toenails as a biomarker of inorganic arsenic intake from drinking water and foodsAbs: Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure."
493,Smith et al. 2006,Increased mortality from lung cancer and bronchiectasis in young adults following exposure to arsenic in utero and in early childhood," Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989-2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30-49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950-1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4-8.9; p<0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3-31.7; p<0.001). For those born during the high-exposure period (1958-1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5-9.9; p<0.001) for lung cancer and 46.2 (95% CI, 21.1-87.7; p<0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.","Increased mortality from lung cancer and bronchiectasis in young adults following exposure to arsenic in utero and in early childhoodAbs: Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989-2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30-49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950-1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4-8.9; p<0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3-31.7; p<0.001). For those born during the high-exposure period (1958-1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5-9.9; p<0.001) for lung cancer and 46.2 (95% CI, 21.1-87.7; p<0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease."
494,Moore et al. 2002,Childhood cancer incidence and arsenic exposure in drinking water in Nevada," Inorganic arsenic exposure through drinking water causes cancer in adults; however, the carcinogenic potential in children remains unknown. A recent leukemia cluster in Churchill County, Nevada, where arsenic levels in water supplies are relatively high, has prompted concern. The authors investigated the incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties, grouped by low (i.e., < 10 microg/l), medium (10-25 microg/l), and high (35-90 microg/l) population-weighted arsenic levels in public drinking water supplies. The standardized incidence ratios (SIRs) for all childhood cancers combined were 1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and 1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties, respectively. There was no relationship between arsenic levels in water and childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90, 1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers, excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI = 0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old children and 10- to 14-yr-old children was in bone cancers, and the excess in 15- to 19-yr-old young adults was primarily in lymphomas. The findings in this study are reassuring in that leukemia risks were not increased at the concentrations of arsenic in water found in this study. Nonetheless, the results raise the possibility that there are increased risks for nonleukemic childhood cancers that require confirmation in other studies, particularly those in which higher exposures are addressed.","Childhood cancer incidence and arsenic exposure in drinking water in NevadaAbs: Inorganic arsenic exposure through drinking water causes cancer in adults; however, the carcinogenic potential in children remains unknown. A recent leukemia cluster in Churchill County, Nevada, where arsenic levels in water supplies are relatively high, has prompted concern. The authors investigated the incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties, grouped by low (i.e., < 10 microg/l), medium (10-25 microg/l), and high (35-90 microg/l) population-weighted arsenic levels in public drinking water supplies. The standardized incidence ratios (SIRs) for all childhood cancers combined were 1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and 1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties, respectively. There was no relationship between arsenic levels in water and childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90, 1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers, excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI = 0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old children and 10- to 14-yr-old children was in bone cancers, and the excess in 15- to 19-yr-old young adults was primarily in lymphomas. The findings in this study are reassuring in that leukemia risks were not increased at the concentrations of arsenic in water found in this study. Nonetheless, the results raise the possibility that there are increased risks for nonleukemic childhood cancers that require confirmation in other studies, particularly those in which higher exposures are addressed."
495,Smith and Smith 2004,Arsenic drinking water regulations in developing countries with extensive exposure," The United States Public Health Service set an interim standard of 50 microg/l in 1942, but as early as 1962 the US Public Health Service had identified 10 microg/l as a goal which later became the World Health Organization Guideline for drinking water in 1992. Epidemiological studies have shown that about one in 10 people drinking water containing 500 microg/l of arsenic over many years may die from internal cancers attributable to arsenic, with lung cancer being the surprising main contributor. A prudent public health response is to reduce the permissible drinking water arsenic concentrations. However, the appropriate regulatory response in those developing countries with large populations with much higher concentrations of arsenic in drinking water, often exceeding 100 microg/l, is more complex. Malnutrition may increase risks from arsenic. There is mounting evidence that smoking and arsenic act synergistically in causing lung cancer, and smoking raises issues of public health priorities in developing countries that face massive mortality from this product. Also, setting stringent drinking water standards will impede short term solutions such as shallow dugwells. Developing countries with large populations exposed to arsenic in water might reasonably be advised to keep their arsenic drinking water standards at 50 microg/l.","Arsenic drinking water regulations in developing countries with extensive exposureAbs: The United States Public Health Service set an interim standard of 50 microg/l in 1942, but as early as 1962 the US Public Health Service had identified 10 microg/l as a goal which later became the World Health Organization Guideline for drinking water in 1992. Epidemiological studies have shown that about one in 10 people drinking water containing 500 microg/l of arsenic over many years may die from internal cancers attributable to arsenic, with lung cancer being the surprising main contributor. A prudent public health response is to reduce the permissible drinking water arsenic concentrations. However, the appropriate regulatory response in those developing countries with large populations with much higher concentrations of arsenic in drinking water, often exceeding 100 microg/l, is more complex. Malnutrition may increase risks from arsenic. There is mounting evidence that smoking and arsenic act synergistically in causing lung cancer, and smoking raises issues of public health priorities in developing countries that face massive mortality from this product. Also, setting stringent drinking water standards will impede short term solutions such as shallow dugwells. Developing countries with large populations exposed to arsenic in water might reasonably be advised to keep their arsenic drinking water standards at 50 microg/l."
496,Smith et al. 2000,Arsenic-induced skin lesions among Atacameo people in Northern Chile despite good nutrition and centuries of exposure," It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.","Arsenic-induced skin lesions among Atacameo people in Northern Chile despite good nutrition and centuries of exposureAbs: It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility."
497,Smith et al. 2009,Increased lung cancer risks are similar whether arsenic is ingested or inhaled," In 1980, the International Agency for Research on Cancer (IARC) determined there was sufficient evidence to support that inorganic arsenic was a human lung carcinogen based on studies involving exposure through inhalation. In 2004, IARC listed arsenic in drinking water as a cause of lung cancer, making arsenic the first substance established to cause human cancer through two unrelated pathways of exposure. It may initially seem counterintuitive that arsenic in drinking water would cause human lung cancer, and even if it did, one might expect risks to be orders of magnitude lower than those from direct inhalation into the lungs. In this paper, we consider lung cancer dose-response relationships for inhalation and ingestion of arsenic by focusing on two key studies, a cohort mortality study in the United States involving Tacoma smelter workers inhaling arsenic, and a lung cancer case-control study involving ingestion of arsenic in drinking water in northern Chile. When exposure was assessed based on the absorbed dose identified by concentrations of arsenic in urine, there was very little difference in the dose-response findings for lung cancer relative risks between inhalation and ingestion. The lung cancer mortality rate ratio estimate was 8.0 (95% CI 3.2-16.5, P<0.001) for an average urine concentration of 1179 microg/l after inhalation, and the odds ratio estimate of the lung cancer incidence rate ratio was 7.1 (95% CI 3.4-14.8, P<0.001) for an estimated average urine concentration of 825 microg/l following ingestion. The slopes of the linear dose-response relationships between excess relative risk (RR-1) for lung cancer and urinary arsenic concentration were similar for the two routes of exposure. We conclude that lung cancer risks probably depend on absorbed dose, and not on whether inorganic arsenic is ingested or inhaled.","Increased lung cancer risks are similar whether arsenic is ingested or inhaledAbs: In 1980, the International Agency for Research on Cancer (IARC) determined there was sufficient evidence to support that inorganic arsenic was a human lung carcinogen based on studies involving exposure through inhalation. In 2004, IARC listed arsenic in drinking water as a cause of lung cancer, making arsenic the first substance established to cause human cancer through two unrelated pathways of exposure. It may initially seem counterintuitive that arsenic in drinking water would cause human lung cancer, and even if it did, one might expect risks to be orders of magnitude lower than those from direct inhalation into the lungs. In this paper, we consider lung cancer dose-response relationships for inhalation and ingestion of arsenic by focusing on two key studies, a cohort mortality study in the United States involving Tacoma smelter workers inhaling arsenic, and a lung cancer case-control study involving ingestion of arsenic in drinking water in northern Chile. When exposure was assessed based on the absorbed dose identified by concentrations of arsenic in urine, there was very little difference in the dose-response findings for lung cancer relative risks between inhalation and ingestion. The lung cancer mortality rate ratio estimate was 8.0 (95% CI 3.2-16.5, P<0.001) for an average urine concentration of 1179 microg/l after inhalation, and the odds ratio estimate of the lung cancer incidence rate ratio was 7.1 (95% CI 3.4-14.8, P<0.001) for an estimated average urine concentration of 825 microg/l following ingestion. The slopes of the linear dose-response relationships between excess relative risk (RR-1) for lung cancer and urinary arsenic concentration were similar for the two routes of exposure. We conclude that lung cancer risks probably depend on absorbed dose, and not on whether inorganic arsenic is ingested or inhaled."
498,Lytle et al. 2004,Accumulation of arsenic in drinking water distribution systems," The tendency for iron solid surfaces to adsorb arsenic is well-known and has become the basis for several drinking water treatment approaches that remove arsenic. It is reasonable to assume that iron-based solids, such as corrosion deposits present in drinking water distribution systems, have similar adsorptive properties and could therefore concentrate arsenic and potentially re-release it into the distribution system. The arsenic composition of solids collected from drinking water distribution systems (pipe sections and hydrant flush solids), where the waters had measurable amounts of arsenic in their treated water, were determined. The elemental composition and mineralogy of 67 solid samples collected from 15 drinking water utilities located in Ohio (7), Michigan (7), and Indiana (1) were also determined. The arsenic content of these solids ranged from 10 to 13 650 microg of As/g of solid (as high as 1.37 wt %), and the major element of most solids was iron. Significant amounts of arsenic were even found in solids from systems that were exposed to relatively low concentrations of arsenic (<10 microg/L) in the water.","Accumulation of arsenic in drinking water distribution systemsAbs: The tendency for iron solid surfaces to adsorb arsenic is well-known and has become the basis for several drinking water treatment approaches that remove arsenic. It is reasonable to assume that iron-based solids, such as corrosion deposits present in drinking water distribution systems, have similar adsorptive properties and could therefore concentrate arsenic and potentially re-release it into the distribution system. The arsenic composition of solids collected from drinking water distribution systems (pipe sections and hydrant flush solids), where the waters had measurable amounts of arsenic in their treated water, were determined. The elemental composition and mineralogy of 67 solid samples collected from 15 drinking water utilities located in Ohio (7), Michigan (7), and Indiana (1) were also determined. The arsenic content of these solids ranged from 10 to 13 650 microg of As/g of solid (as high as 1.37 wt %), and the major element of most solids was iron. Significant amounts of arsenic were even found in solids from systems that were exposed to relatively low concentrations of arsenic (<10 microg/L) in the water."
499,Soto-Pena et al. 2006,Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic," Exposure of several human populations to arsenic has been associated with a high incidence of detrimental dermatological and carcinogenic effects. To date, studies examining the immunotoxic effects of arsenic in humans, and specifically in children, are lacking. Therefore, we evaluated several parameters of immunological status in a group of children exposed to arsenic through their drinking water. Peripheral blood mononuclear cells (PBMCs) of 90 children (6 to 10 years old) were collected. Proportions of lymphocyte subpopulations, PBMC mitogenic proliferative response, and urinary arsenic levels were evaluated. Increased urine arsenic levels were associated with a reduced proliferative response to phytohemaglutinin (PHA) stimulation (P=0.005), CD4 subpopulation proportion (P=0.092), CD4/CD8 ratio (P=0.056), and IL-2 secretion levels (P=0.003). Increased arsenic exposure was also associated with an increase in GM-CSF secretion by mononucleated cells (P=0.000). We did not observe changes in CD8, B, or NK cell proportions, nor did we observe changes in the secretion of IL-4, IL-10, or IFN-gamma by PHA-activated PBMCs. These data indicate that arsenic exposure could alter the activation processes of T cells, such that an immunosuppression status that favors opportunistic infections and carcinogenesis is produced together with increased GM-CSF secretion that may be associated with chronic inflammation.","Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenicAbs: Exposure of several human populations to arsenic has been associated with a high incidence of detrimental dermatological and carcinogenic effects. To date, studies examining the immunotoxic effects of arsenic in humans, and specifically in children, are lacking. Therefore, we evaluated several parameters of immunological status in a group of children exposed to arsenic through their drinking water. Peripheral blood mononuclear cells (PBMCs) of 90 children (6 to 10 years old) were collected. Proportions of lymphocyte subpopulations, PBMC mitogenic proliferative response, and urinary arsenic levels were evaluated. Increased urine arsenic levels were associated with a reduced proliferative response to phytohemaglutinin (PHA) stimulation (P=0.005), CD4 subpopulation proportion (P=0.092), CD4/CD8 ratio (P=0.056), and IL-2 secretion levels (P=0.003). Increased arsenic exposure was also associated with an increase in GM-CSF secretion by mononucleated cells (P=0.000). We did not observe changes in CD8, B, or NK cell proportions, nor did we observe changes in the secretion of IL-4, IL-10, or IFN-gamma by PHA-activated PBMCs. These data indicate that arsenic exposure could alter the activation processes of T cells, such that an immunosuppression status that favors opportunistic infections and carcinogenesis is produced together with increased GM-CSF secretion that may be associated with chronic inflammation."
500,Soucy et al. 2005,Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice," Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease.","Neovascularization and angiogenic gene expression following chronic arsenic exposure in miceAbs: Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease."
