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. Ojectives: 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. Results: 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. Conclusions: 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

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

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

An Eight-year Study Report on Arsenic Contamination in Groundwater and Health Effects in Eruani Village, Bangladesh and an Approach for Its Mitigation

Based on several surveys during 1997-2005 and visits of a medical team to Eruani village, Laksham upazila, Comilla district, Bangladesh, the arsenic contamination situation and consequent clinical manifestations of arsenicosis among the villagers, including dermatology, neuropathy, and obstetric outcome, are reported here. Analysis of biological samples from patients and non-patients showed high body burden of arsenic. Even after eight years of known exposure, village children were still drinking arsenic-contaminated water, and many of them had arsenical skin lesions. There were social problems due to the symptoms of arsenicosis. The last survey established that there is a lack of proper awareness among villagers about different aspects of arsenic toxicity. The viability of different options of safe water, such as dugwells, deep tubewells, rainwater harvesting, and surface water with watershed management in the village, was studied. Finally, based on 19 years of field experience, it was felt that, for any successful mitigation programme, emphasis should be given to creating awareness among villagers about the arsenic problem, role of arsenic-free water, better nutrition from local fruits and vegetables, and, above all, active participation of women along with others in the struggle against the arsenic menace

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

An Eight-year Study Report on Arsenic Contamination in Groundwater and Health Effects in Eruani Village, Bangladesh and an Approach for Its Mitigation

Based on several surveys during 1997-2005 and visits of a medical team to Eruani village, Laksham upazila, Comilla district, Bangladesh, the arsenic contamination situation and consequent clinical manifestations of arsenicosis among the villagers, including dermatology, neuropathy, and obstetric outcome, are reported here. Analysis of biological samples from patients and non-patients showed high body burden of arsenic. Even after eight years of known exposure, village children were still drinking arsenic-contaminated water, and many of them had arsenical skin lesions. There were social problems due to the symptoms of arsenicosis. The last survey established that there is a lack of proper awareness among villagers about different aspects of arsenic toxicity. The viability of different options of safe water, such as dugwells, deep tubewells, rainwater harvesting, and surface water with watershed management in the village, was studied. Finally, based on 19 years of field experience, it was felt that, for any successful mitigation programme, emphasis should be given to creating awareness among villagers about the arsenic problem, role of arsenic-free water, better nutrition from local fruits and vegetables, and, above all, active participation of women along with others in the struggle against the arsenic menace