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Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators- interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators- interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Groundwater, the major source of drinking water in Bengal Delta Plain, is contaminated with geogenic arsenic (As) enrichment affecting millions of people. Children exposed to tubewell water containing As may be associated with thyroid dysfunction, which in turn may impact neurodevelopmental outcomes. However, data to support such relationship is sparse. The purpose of this study was to examine if chronic water As (WAs) from Holocene alluvial aquifers in this region was associated with serum thyroid hormone (TH) and if TH biomarkers were related to neurobehavioral (NB) performance in a group of adolescents. A sample of 32 healthy adolescents were randomly drawn from a child cohort in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh. Half of these participants were consistently exposed to low WAs (<10 μg/L) and the remaining half had high WAs exposure (≥10 μg/L) since birth. Measurements included serum total triiodothyronine (tT 3 ), free thyroxine (fT 4 ), thyrotropin (TSH) and thyroperoxidase antibodies (TPOAb); concurrent WAs and urinary arsenic (UAs); and adolescents' NB performance. WAs and UAs were positively and significantly correlated with TPOAb but were not correlated with TSH, tT 3 and fT 4 . After accounting for covariates, both WAs and UAs demonstrated positive but non-significant relationships with TSH and TPOAb and negative but non-significant relationships with tT 3 and fT 4 . TPOAb was significantly associated with reduced NB performance indicated by positive associations with latencies in simple reaction time (b = 82.58; p < 0.001) and symbol digit (b = 276.85; p = 0.005) tests. TSH was significantly and negatively associated with match-to-sample correct count (b = -0.95; p = 0.05). Overall, we did not observe significant associations between arsenic exposure and TH biomarkers although the relationships were in the expected directions. We observed TH biomarkers to be related to reduced NB performance as hypothesized. Our study indicated a possible mechanism of As-induced neurotoxicity, which requires further investigations for confirmatory findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex., Methods: We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions., Results: We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L) compared to women with normal hemoglobin levels [Odds Ratio (OR) = 3.32, 95% Confidence Intervals (CI): 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75% of the women with anemia had adequate iron stores (serum ferritin ≥ 12 μg/L), suggesting that the majority of anemia detected in this population was unrelated to iron depletion., Conclusions: Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time., (Copyright © 2015. Published by Elsevier Inc.)

Cyanobacterial blooms commonly appear during the summer months in ponds, lakes and reservoirs in Bangladesh. In these areas, fish mortality, odorous water and fish and human skin irritation and eye inflammation have been reported. The influence of physicochemical factors on the occurrence of cyanobacteria and its toxin levels were evaluated in natural and drinking water in Bangladesh. A highly sensitive immunosorbent assay was used to detect microcystins (MCs). Cyanobacteria were found in 22 of 23 samples and the dominant species were Microcystis aeruginosa, followed by Microcystisflosaquae, Anabeana crassa and Aphanizomenon flosaquae. Cyanobacterial abundance varied from 39 to 1315 x 10(3) cells mL(-1) in natural water and 31 to 49 x 10(3) cells mL(-1) in tap water. MC concentrations were 25-82300 pg mL(-1) with the highest value measured in the fish research pond, followed by Ishakha Lake. In tap water, MC concentrations ranged from 30-32 pg mL(-1). The correlation between nitrate-nitrogen (NO3-N) concentration and cyanobacterial cell abundance was R2 = 0.62 while that between cyanobacterial abundance and MC concentration was R2 = 0.98. The increased NO3-N from fish feed, organic manure, poultry and dairy farm waste and fertilizer from agricultural land eutrophicated the water bodies and triggered cyanobacterial bloom formation. The increased amount of cyanobacteria produced MCs, subsequently reducing the water quality.

Heavy-metal pollution occurs in various environments, including water, air and soil, and has serious effects on human health. Since heavy-metal pollution in drinking water causes various diseases including skin cancer, it has become a global problem worldwide. However, there is limited information on the mechanism of development of heavy-metal-mediated disease. We performed both fieldwork and experimental studies to elucidate the levels of heavy-metal pollution and mechanisms of development of heavy-metal-related disease and to develop a novel remediation system. Our fieldwork in Bangladesh, Vietnam and Malaysia demonstrated that drinking well water in these countries was polluted with high concentrations of several heavy metals including arsenic, barium, iron and manganese. Our experimental studies based on the data from our fieldwork demonstrated that these heavy metals caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system with which toxic heavy metals were absorbed from polluted drinking water. Implementation of both fieldwork and experimental studies is important for prediction, prevention and therapy of heavy-metal-mediated diseases.

Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Data on the role of arsenic in renal cancer are suggestive but inconclusive. The present analysis aimed to determine whether renal cancers were more likely in Bangladeshi villagers exposed to high arsenic concentration in well water and, if so, whether this excess was limited to transitional cell cancers (TCC) or occurred also for renal cell cancers (RCC)., Methods: Histology/cytology results from renal biopsies carried out at a single clinic in Dhaka, Bangladesh, from January 2008 to October 2011 were classified into four groups: RCC, TCC, other malignancy and benign. Patients aged ≥18 years using hand-pumped well water were identified by questionnaire, blind to diagnosis. Arsenic concentration was estimated from British Geological Survey reports for administrative area (thana) of residence. In a case-referent design (with benign results as referents), ORs were calculated by multilevel logistic regression adjusted for confounding. Time since well installation and smoking were examined by stratification., Results: Among 1489 cases included, 896 were RCC, 90 TCC and 503 benign. Arsenic concentration was estimated for 301 thanas with 63% of cases and 40% referents with arsenic concentration ≥50 µg/L (p<0.001). Risk increased monotonically with arsenic concentration ≥50 µg/L for both cell types (RCC and TCC). Risk estimates were greater in thana with early well installation where risk was increased for RCC in exposure stratum 10<50 µg/L (OR=2.47 95% CI 1.52 to 4.01). Stratification by 'ever smoked' confirmed the presence of risk in non-smokers., Conclusions: The relationship between arsenic concentration and both RCC and TCC suggests that arsenic is a causal factor in renal cancer.

Objective: To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh., Methods: We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study, which is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions., Results: Participants with high urinary arsenic levels (286.1 to 5000.0 μg/g) were more likely to develop arsenical lesions of the gums (multinomial odds ratio = 2.90; 95% confidence interval, 1.11 to 7.54), and tongue (multinomial odds ratio = 2.79; 95% confidence interval, 1.51 to 5.15), compared with those with urinary arsenic levels of 7.0 to 134.0 μg/g., Conclusions: Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue.

A national drinking water quality survey conducted in 2009 furnished data that were used to make an updated estimate of chronic arsenic exposure in Bangladesh. About 20 million and 45 million people were found to be exposed to concentrations above the national standard of 50 µg/L and the World Health Organization's guideline value of 10 µg/L, respectively. From the updated exposure data and all-cause mortality hazard ratios based on local epidemiological studies, it was estimated that arsenic exposures to concentrations > 50 µg/L and 10-50 µg/L account for an annual 24,000 and perhaps as many as 19,000 adult deaths in the country, respectively. Exposure varies widely in the 64 districts; among adults, arsenic-related deaths account for 0-15% of all deaths. An arsenic-related mortality rate of 1 in every 16 adult deaths could represent an economic burden of 13 billion United States dollars (US$) in lost productivity alone over the next 20 years. Arsenic mitigation should follow a two-tiered approach: (i) prioritizing provision of safe water to an estimated 5 million people exposed to > 200 µg/L arsenic, and (ii) building local arsenic testing capacity. The effectiveness of such an approach was demonstrated during the United Nations Children's Fund 2006-2011 country programme, which provided safe water to arsenic-contaminated areas at a cost of US$ 11 per capita. National scale-up of such an approach would cost a few hundred million US dollars but would improve the health and productivity of the population, especially in future generations.

Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 μg/L) and Mn (above and below 500 μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001-2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log(10) percentage of MMA (adjusted odds ratio (OR(adj)) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log(10) percentage of inorganic arsenic (OR(adj) = 1.06, 95% CI: 0.75, 1.50) or log(10) percentage of DMA (OR(adj) = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors.

Background: Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population., Methods: In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure., Findings: 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate., Interpretation: Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure., Funding: US National Institutes of Health., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE) activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh., Methods: A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 +/- 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low (< 129 microg/L), medium (130-264 microg/L) and high (> 265 microg/L). Study subjects were further sub-divided into two groups ( 50 microg/L) based on the recommended upper limit of water arsenic concentration (50 microg/L) in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PChE activity was assayed by spectrophotometer., Results: Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 microg/L group compared to the

Background: Arsenic is a known carcinogen but the risk of lung cancer from the widespread contamination of drinking water in rural Bangladesh has not been estimated., Objectives: To determine whether estimated exposure of villagers in Bangladesh to arsenic in drinking water differed between those with lung cancer and those with non-malignant lesions., Methods: Data were obtained from 7286 subjects who underwent lung biopsy in 2003-2006 at a diagnostic centre taking referrals from throughout Bangladesh. Analysis was limited to 5372 people living in villages for the last 10 years who reported using tube well water. Of these, 3223 with a primary lung tumour were enrolled as cases and 1588 with non-malignant lesions as referents in an unmatched analysis. Arsenic exposure was estimated by average concentrations for each of 64 districts. Logistic regression was used to test the effects of age, arsenic and smoking on risk and to investigate relationship to cell type., Results: Male cases were older than referents and more likely to smoke, to smoke >20 units/day and to smoke bidi-small, hand-rolled cigarettes. Odds ratios for lung cancer increased steadily with mean arsenic concentration, but the confidence interval excluded 1.0 only at concentrations >100 mug/l (OR 1.45, 95% CI 1.16 to 1.80). This trend was seen only in smokers where the increased risk at >100 mug/l was 1.65 (95% CI 1.25 to 2.18). A similar trend was seen in women smokers. Squamous cell lung cancer was more frequent in smokers and, having adjusted for smoking, in districts with arsenic concentrations >100 mug/l., Conclusions: Among Bangladeshis who smoke, those whose drinking water is contaminated with arsenic at concentrations >100 mug/l are at increased risk of lung cancer. With high levels of exposure misclassification and short latency of exposure, the study cannot estimate or exclude the likely long term risk in non-smokers and at lower arsenic concentrations.

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 53 km 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 < 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.

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.

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.

Background: Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water., Objective: The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenic-induced alterations in DNA methylation may be influenced by folate nutritional status., Design: PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [(3)H]-methyl incorporation assay., Results: Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P = 0.009, 0.03, and 0.03, respectively). Stratification of participants by folate nutritional status [<9 nmol/L (n = 190) or >or=9 nmol/L (n = 104)] showed that the associations between arsenic exposure and methylation of PBL DNA were restricted to persons with folate concentrations >or= 9 nmol/L., Conclusions: Contrary to our a priori hypothesis, arsenic exposure was positively associated with genomic PBL DNA methylation in a dose-dependent manner. This effect is modified by folate, which suggests that arsenic-induced increases in DNA methylation cannot occur in the absence of adequate folate. The underlying mechanisms and physiologic implications of increased genomic DNA methylation are unclear, and they warrant further study.

We conducted a case-control study to investigate interindividual variability in susceptibility to health effects of inorganic arsenic due to arsenic metabolism efficiency, genetic factors, and their interaction. A total of 594 cases of arsenic-induced skin lesions and 1,041 controls was selected from baseline participants in a large prospective cohort study in Bangladesh. Adjusted odds ratios (OR) for skin lesions were estimated in relation to the polymorphisms in the glutathione S-transferase omega1 and methylenetetrahydrofolate reductase genes, the percentage of monomethylarsonous acid (%MMA) and dimethylarsinic acid (%DMA) in urine, and the ratios of MMA to inorganic arsenic and DMA to MMA. Water arsenic concentration was positively associated with %MMA and inversely associated with %DMA. The dose-response relationship of risk of skin lesion with %MMA was more apparent than those with other methylation indices; the ORs for skin lesions in relation to increasing %MMA quartiles were 1.00 (reference), 1.33 [95% confidence interval (95% CI), 0.92-1.93], 1.68 (95% CI, 1.17-2.42), and 1.57 (95% CI, 1.10-2.26; P for trend = 0.01). The ORs for skin lesions in relation to the methylenetetrahydrofolate reductase 677TT/1298AA and 677CT/1298AA diplotypes (compared with 677CC/1298CC diplotype) were 1.66 (95% CI, 1.00-2.77) and 1.77 (95% CI, 0.61-5.14), respectively. The OR for skin lesions in relation to the glutathione S-transferase omega1 diplotype containing all at-risk alleles was 3.91 (95% CI, 1.03-14.79). Analysis of joint effects of genotypes/diplotypes with water arsenic concentration and urinary %MMA suggests additivity of these factors. The findings suggest that arsenic metabolism, particularly the conversion of MMA to DMA, may be saturable and that differences in urinary arsenic metabolites, genetic factors related to arsenic metabolism, and their joint distributions modulate arsenic toxicity.

A glass house experiment was conducted to investigate the effect of soil arsenic on photosynthetic pigments, chlorophyll-a and -b, and their correlations with rice yield and growth. The experiment was designed with three replications of six arsenic treatments viz. control, 10, 20, 30, 60, 90 mg of As kg(-1) soil. Arsenic concentration in initial soil, to which the above mentioned concentrations of arsenic were added, was 6.44+/-0.24 mg kg(-1). Both chlorophyll-a and -b contents in rice leaf decreased significantly (p<0.05) with the increase of soil arsenic concentrations. No rice plant survived up to maturity stage in soil treated with 60 and 90 mg of As kg(-1). The highest chlorophyll-a and -b contents were observed in control treatment (2.62+/-0.24 and 2.07+/-0.14 mg g(-1) were the average values of chlorophyll-a and -b, respectively of the five rice varieties) while 1.50+/-0.20 and 1.04+/-0.08 mg g(-1) (average of five rice varieties) of chlorophyll-a and -b, respectively were the lowest. The content of photosynthetic pigments in these five rice varieties did not differ significantly (p>0.05) from each other in control treatment though they differed significantly (p<0.05) from each other in 30 mg of As kg(-1) soil treatment. Among the five rice varieties, chlorophyll content in BRRI dhan 35 was found to be mostly affected with the increase of soil arsenic concentration while BRRI hybrid dhan 1 was least affected. Well correlations were observed between chlorophyll content and rice growth and yield suggesting that arsenic toxicity affects the photosynthesis which ultimately results in the reduction of rice growth and yield.

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.

A survey was carried out to provide a representative assessment of prevalence and risk of arsenic-related skin lesions in relation to geographical distribution of arsenic in wells of rural Bangladesh as a necessary background for research into effects in pregnancy and cancer risks. A systematic random sample of 53 villages in four divisions of Bangladesh served by Gonoshasthaya Kendra was selected, and all women aged 18 years or more (n=16,740) were listed. Trained paramedics recorded the presence of skin thickening and nodules on the palms and soles, together with information on tubewell use. The prevalence was related to the mean concentration of arsenic for the district as indicated by data from the British Geological Survey and to the date the first well in the village was installed. Overall, the observed prevalence was 176 cases (1.3%) in 13,705 women examined, varying from 0% in 26 villages to 23% in one; lesions were observed more frequently on hands than on feet. The estimate doubled with concentrations of arsenic from 11 to < or =50 microg/L and increased more than 20 times at >50 microg/L. In the absence of further information, priority for control measures should be directed at areas where the average concentrations of arsenic are above 50 microg/L, especially in villages where skin lesions have been identified.

This study assessed the exposure of pregnant women to arsenic in Matlab, Bangladesh, an area with highly-elevated concentrations of arsenic in tubewells, by measuring concentrations of arsenic in urine. In a defined administrative area, all new pregnancies were identified by urine test in gestational week 6-8, and women were asked to participate in the assessment of arsenic exposure. Urine for analysis of arsenic was collected immediately and in gestational week 30. In total, 3,426 pregnant women provided urine samples during January 2002-March 2003. There was a considerable variation in urinary concentrations of arsenic (total range 1-1,470 microg/L, adjusted to specific gravity 1.012 g/mL), with an overall median concentration of 80 microg/L (25th and 75th percentiles were 37 and 208 microg/L respectively). Similar concentrations were found in gestational week 30, indicating no trend of decreasing exposure, despite the initiation of mitigation activities in the area. Arsenic exposure was negatively associated with socioeconomic classes and achieved educational level. There were marked geographical variations in exposure. The results emphasize the urgent need for efficient mitigation activities and investigations of arsenic-related reproductive effects.

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.

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.

Besides its toxicity, groundwater arsenic contamination creates widespread social problems for its victims and their families in Bangladesh. There is, for instance, a tendency to ostracise arsenic-affected people, arsenicosis being thought of as a contagious disease. Within the community, arsenic-affected people are barred from social activities and often face rejection, even by their immediate family members. Women with visible arsenicosis symptoms are unable to get married and some affected housewives are divorced by their husbands. Children with symptoms are not sent to school in an effort to hide the problem. This paper employs mainly qualitative methods to interpret people's understandings about the toxic impact of groundwater arsenic poisoning on their social lives. Arsenic-affected patients in southwest Bangladesh were asked to determine their 'own priorities' in measuring arsenic toxicity on their social activities and to explore their perceptions about their own survival strategies. We found that patients' experiences reveal severe negative social impacts, and a sharp difference of perceptions about arsenic and social issues between arsenicosis patients and unaffected people.

Only after a decade from 1993, arsenic contamination of groundwater in Bangladesh has been reported as the biggest arsenic catastrophe in the world. It is a burning public health issue in this country. More than 50 percent of the total population is estimated at risk of contamination. Already thousands of people have been affected by the disease arsenicosis. Many more may be on the way to manifest lesions in future. We conducted a review of previous studies and published articles including MEDLINE database on this issue. We found that 59 districts out of 64 have been already affected by arsenic in underground drinking water, where this particular source of drinking water is the main source for 97 percent of the rural people. The water is unfortunately now a great threat for the human being due to high level of arsenic. Continuous arsenic exposure can lead people to develop arsenicosis, which in turn elevates the risk of cancer. Skin lesions are the most common manifestations in arsenicosis patients. Relatively poor rural people and other socio-economically disadvantaged groups are more affected by this exposure. Until now cancer patients have been relatively limited in Bangladesh. One of the reasons may be that several years are needed to show cancer manifestations from the beginning of arsenic exposure. But it is suspected that after some years a large number of patients will appear with cancer in different sites for arsenic exposure in drinking water. Various studies have been conducted in arsenic affected countries - notably in Argentina, Chile, China, Japan, and Taiwan -to find the potential of arsenic exposure to cause development of cancer. Among the arsenic related cancers, liver, lung, skin, bladder and kidney cancers are reported to be prevalent in these countries. Unfortunately no scientific study has been yet conducted in Bangladesh to find the relationship between arsenic exposure and cancers in different sites of the body. So our aim is to conduct an ecological as well as a case-control study in the country in the future.

-A prevalence comparison of hypertension among subjects with and those without arsenic exposure through drinking water was conducted in Bangladesh to confirm or refute an earlier observation of a relation in this respect. Wells with and without present arsenic contamination were identified, and we interviewed and examined 1595 subjects who were depending on drinking water from these wells for living, all >/=30 years of age. The interview was based on a questionnaire, and arsenic exposure was estimated from the history of well-water consumption and current arsenic levels. Of the 1595 subjects studied, 1481 had a history of arsenic-contaminated drinking water, whereas 114 had not. Time-weighted mean arsenic levels (in milligrams per liter) and milligram-years per liter of arsenic exposure were estimated for each subject. Exposure categories were assessed as <0.5 mg/L, 0.5 to 1.0 mg/L, and >1.0 mg/L and alternatively as <1.0 mg-y/L, 1.0 to 5.0 mg-y/L, >5.0 but 10.0 mg-y/L, respectively. Hypertension was defined as a systolic blood pressure of >/=140 mm Hg in combination with a diastolic blood pressure of >/=90 mm Hg. Corresponding to the exposure categories, and using "unexposed" as the reference, the prevalence ratios for hypertension adjusted for age, sex, and body mass index were 1.2, 2.2, 2.5 and 0.8, 1.5, 2.2, 3.0, in relation to arsenic exposure in milligrams per liter and milligram-years per liter, respectively. The indicated dose-response relationships were significant (P<<0.001) for both series of risk estimates. These results suggest that arsenic exposure may induce hypertension in humans.