A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000-2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).     

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.     

Spontaneous pregnancy loss in humans and exposure to arsenic in drinking water

Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss.     

Lifetime exposure to arsenic in residential drinking water in Central Europe

Objective

Methods and results are presented for an arsenic exposure assessment integral to an epidemiological case–control study of arsenic and cancer—the European Commission funded ASHRAM (Arsenic Health Risk Assessment and Molecular Epidemiology) study carried out in some counties of Hungary, Romania and Slovakia.

Methods

The exposure history of each participant (N = 1,392) was constructed by taking into account how much water they consumed (as water, in drinks and in food), sources of drinking water in their various residences over their lifetime, and the concentrations of arsenic in their various water supplies measured by Hydride Generation-Atomic Absorption Spectrometry (HG-AAS). Concentrations of arsenic in previous water supplies were either derived from contemporary analyses of the same source, or from routine historical data from measurements performed by the authorities in each country. Using this approach, 80% of the recorded lifetime residential history was matched to an arsenic concentration. Seven indices of current, life time, and peak exposure were calculated.

Results

The exposure indices were all log-normally distributed and the mean and median lifetime average concentrations were in Hungary 14.7 and 13.3 μg l^?1, Romania 3.8 and 0.7 μg l^?1 and in Slovakia 1.9 and 0.8 μg l^?1, respectively. Overall 25% of the population had average concentrations over 10 μg l^?1 and 8% with exposure over 50 μg l^?1.

Conclusions

Careful assessment of arsenic in drinking water supplies (both current and previous) enabled the majority of study participants’ cumulative lifetime of potential exposure to arsenic in residential water to be characterised.     

Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 μg/day compared to 0.6 to 3.4 μg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 μg/L) whereas a high of 2.0 μg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.     

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.     

饮水型砷暴露对人群甲基化代谢能力的影响

目的探讨饮水型砷暴露对人群甲基化代谢能力的影响。方法以带有砷化物预处理装置的原子吸收分光光度计测定砷暴露人群及无砷暴露对照人群血、尿中无机砷(iAs)、甲基胂(MMA)、二甲基胂(DMA)含量。以iAs、MMA及DMA的总和表示总胂(tAs)水平;以(MMA+DMA)/tAs及DMA/(MMA+DMA)分别计算一甲基化率(PMI)和二甲基化率(SMI)水平。结果砷暴露人群血中iAs、MMA、DMA、tAs及PMI水平均显著高于相应对照人群的水平,而SMI水平显著低于对照人群。尿中MMA水平分别与血中PMI及SMI水平呈显著正相关(r=0.419,P<0.01)及负相关(r=-0.326,P<0.05)。暴露组和对照组血中各种砷化物水平及甲基化率水平在男女间差异无显著性。结论砷暴露人群与无砷暴露人群相比甲基化率有差异,PMI显著增高,SMI显著降低。人群甲基化率无显著性别差异。     

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water

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.     

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.     

Chlorination of drinking water and cancer incidence in Norway.

To examine whether chlorination of drinking water was associated with cancer of the digestive or other organs, an ecological epidemiological study using nationwide incidence data from the Cancer Registry of Norway was carried out. On two geographical levels (counties and municipalities), both for men and women, chlorination of drinking water was associated with an increased incidence of cancer of the colon and rectum. After adjusting for potential confounding variables, also measured on a geographical basis, the associations were still significant at the county level (adjusted for population density, income, education, fat and fibre intake etc.), but not at the municipality level. The observed associations are weak, chlorination being associated with a 20-40% increase in colorectal cancer rates. Due to inherent methodological limitations in ecological studies like the present one, causal interpretations should be made with great care. Thus, although the results give some support to the hypothesis that drinking water chlorination is associated with colorectal cancer, they do not provide strong evidence of a causal relationship.     

Cancer incidence following exposure to drinking water with asbestos leachate

In November 1985, the New York State Department of Health was altered to extraordinary concentrations of asbestos leachate in the drinking water in the Town of Woodstock. Concentrations of 3.2 million fibers per liter (MFL) to 304.5 MFL were found, depending on location. An investigation of cancer incidence in the area was conducted for the period 1973-83 using the State Cancer Registry to compute standardized incidence ratios. No evidence was found of elevated cancer incidence at sites associated with asbestos exposure. A statistically non-significant excess of kidney cancer was seen among men, but not women. Colon cancer among men was significantly low, but incidence among women was similar to that expected. Lung cancer incidence was lower than expected for both sexes. Ovarian cancer rates were not different from expected rates. At sites not previously related to asbestos exposure, cancer of the oral cavity was significantly high, with most affected persons having a history of cigarette smoking. Surveillance of the community is continuing because of an insufficient latent period for some exposed groups.     

Longitudinal investigation of exposure to arsenic, cadmium, and lead in drinking water

Arsenic, cadmium, and lead have been associated with various forms of cancer, nephrotoxicity, central nervous system effects, and cardiovascular disease in humans. Drinking water is a well-recognized pathway of exposure to these metals. To improve understanding of the temporal dimension of exposure to As, Cd, and Pb in drinking water, we obtained 381 samples of tap and/or tap/filtered water and self-reported rates of drinking water consumption from 73 members of a stratified random sample in Maryland. Data were collected at approximately 2-month intervals from September 1995 through September 1996. Concentrations of As (range < 0.2-13.8 microg/L) and Pb (< 0.1-13.4 microg/L) were within the ranges reported for the United States, as were the rates of drinking water consumption (median < 0.1-4.1 L/day). Cd was present at a detectable level in only 8.1% of the water samples. Mean log-transformed concentrations and exposures for As and Pb varied significantly among sampling cycles and among respondents, as did rates of drinking water consumption, according to a generalized linear model that accounted for potential correlation among repeated measures from the same respondent. We used the intraclass correlation coefficient of reliability to attribute the total variance observed for each exposure metric to between-person and within-person variability. Between-person variability was estimated to account for 67, 81, and 55% of the total variance in drinking water consumption, As exposure (micrograms per day), and Pb exposure (micrograms per day), respectively. We discuss these results with respect to their implications for future exposure assessment research, quantitative risk assessment, and environmental epidemiology.     

Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.     

Nonmalignant respiratory effects of chronic arsenic exposure from drinking water among never-smokers in Bangladesh

BACKGROUND: Arsenic from drinking water has been associated with malignant and nonmalignant respiratory illnesses. The association with nonmalignant respiratory illnesses has not been well established because the assessments of respiratory symptoms may be influenced by recall bias or interviewer bias because participants had visible skin lesions. OBJECTIVES: We examined the relationship of the serum level of Clara cell protein CC16--a novel biomarker for respiratory illnesses--with well As, total urinary As, and urinary As methylation indices. METHODS: We conducted a cross-sectional study in nonsmoking individuals (n = 241) selected from a large cohort with a wide range of As exposure (0.1-761 microg/L) from drinking water in Bangladesh. Total urinary As, urinary As metabolites, and serum CC16 were measured in urine and serum samples collected at baseline of the parent cohort study. RESULTS: We observed an inverse association between urinary As and serum CC16 among persons with skin lesions (beta = -0.13, p = 0.01). We also observed a positive association between secondary methylation index in urinary As and CC16 levels (beta = 0.12, p = 0.05) in the overall study population; the association was stronger among people without skin lesions (beta = 0.18, p = 0.04), indicating that increased methylation capability may be protective against As-induced respiratory damage. In a subsample of study participants undergoing spirometric measures (n = 31), we observed inverse associations between urinary As and predictive FEV(1) (forced expiratory volume measured in 1 sec) (r = -0.37; FEV(1)/forced vital capacity ratio and primary methylation index (r = -0.42, p = 0.01). CONCLUSIONS: The findings suggest that serum CC16 may be a useful biomarker of epithelial lung damage in individuals with arsenical skin lesions. Also, we observed the deleterious respiratory effects of As exposure at concentrations lower than reported in earlier studies.     

Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2,100 ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12 ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16 ppm. Significant (P<0.0001) positive regressions were seen between the TAs concentration in toenails and in drinking water (adjusted r(2)=0.3557 HG-AFS, adjusted r(2)=0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r(2)=0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine.     

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.     

Case-control study of bladder cancer and drinking water arsenic in the western United States

Numerous epidemiologic investigations have identified links between high concentrations of arsenic in drinking water and cancer, although the risks at lower exposures are largely unknown. This paper presents the results of a case-control study of arsenic ingestion and bladder cancer in seven counties in the western United States. These counties contain the largest populations historically exposed to drinking water arsenic at concentrations near 100 microg/liter. All incident cases diagnosed from 1994 to 2000 were recruited. Individual data on water sources, water consumption patterns, smoking, and other factors were collected for 181 cases and 328 controls. Overall, no increased risks were identified for arsenic intakes greater than 80 microg/day (odds ratio=0.94, 95% confidence interval: 0.56, 1.57; linear trend, p=0.48). These risks are below predictions based on high dose studies from Taiwan. When the analysis was focused on exposures 40 or more years ago, an odds ratio of 3.67 (95% confidence interval: 1.43, 9.42; linear trend, p<0.01) was identified for intakes greater than 80 microg/day (median intake, 177 microg/day) in smokers. These data provide some evidence that smokers who ingest arsenic at concentrations near 200 microg/day may be at increased risk of bladder cancer.