Levels Of Arsenic In Drinking Water Research Articles

Meta-analysis of the relationship between maternal arsenic exposure and preterm birth

To systematic evaluate the association between maternal arsenic exposure and preterm birth. A literature search was conducted through Pubmed, Web of Science, Embase, China Knowledge Network(CNKI), WanFang Data, Vip Chinese Journal Service Platform(VIP) with a time frame of November 2022 from the beginning of database construction. Meta-analysis of dichotomous variables was performed using Stata MP15 software, and a random or fixed effects model was chosen for the meta-analysis based on the heterogeneity result, with the ratio of ratios(OR) as the effect indicator; subgroup analysis was used to find characteristic changes; funnel plots were used to evaluate publication bias. A total of 15 papers with a sample size of(n=9 892 256 279), 10 prospective cohort studies, 3 retrospective cohort studies, and 2 cross-sectional studies, were included in 6 Chinese and 9 English papers. By Meta-analysis, the combined OR of preterm birth outcome was 1.06(95%CI 1.03-1.09); the result of subgroup analysis by exposure factors and region, the combined OR(95%CI) of hair, blood, urine, drinking water, and placenta were 0.97(0.56-1.69), 1.40(1.22-1.60), 1.04(0.93-1.17), 1.14(1.04-1.24) and 0.69(0.07-6.38). The combined OR(95%CI) were 1.17(1.04-1.31), 1.10(1.05-1.14), 0.69(0.07-6.38) and 1.17(1.01-1.36) for Asia, Americas, Europe and Africa, respectively. For subgroup analysis based on study type, the combined OR(95%CI) was 1.16(1.05-1.28), 1.01(1.01-1.02) and 1.65(0.73-3.74) for prospective cohort studies, retrospective cohort studies, and cross-sectional studies, respectively. Maternal arsenic exposure may contribute to the occurrence of preterm birth, and drinking water arsenic levels may be an important indicator for assessing human arsenic exposure and risk of causing preterm birth.

Testing the Limit: Evaluating Drinking Water Arsenic Regulatory Levels Based on Adverse Pregnancy Outcomes in Bangladesh.

(1) Background: Arsenic (As) is a common drinking water contaminant that is regulated as a carcinogen. Yet, As is a systemic toxicant and there is considerable epidemiological data showing As adversely impacts reproductive health. This study used data from a birth cohort in Bangladesh (2008–2011) to examine associations between drinking water As levels and reproductive outcomes. (2) Methods: Pregnant individuals (n = 1597) were enrolled at <16 weeks gestation and drinking water As was measured. Participants with live births (n = 1130) were propensity score matched to participants who experienced miscarriage (n = 132), stillbirth (n = 72), preterm birth (n = 243), and neonatal mortality (n = 20). Logistic regression was used to examine drinking water As recommendations of 50, 10, 5, 2.5, and 1 µg/L on the odds of adverse birth outcomes. (3) Results: The odds of miscarriage were higher for pregnant women exposed to drinking water ≥2.5 versus <2.5 µg As/L [adjusted odds ratio (OR) 1.90, 95% Confidence Interval (CI): 1.07–3.38)]. (4) Conclusions: These preliminary findings suggest a potential threshold where the odds of miscarriage increases when drinking water As is above 2.5 µg/L. This concentration is below the World Health Organizations and Bangladesh’s drinking water recommendations and supports the re-evaluation of drinking water regulations.

Spatial relationship between well water arsenic and uranium in Northern Plains Native lands

BACKGROUND AND AIM: Arsenic and uranium in unregulated private wells affect many rural populations across the US, including American Indian communities. The current EPA maximum contaminant level (MCL) is 10 µg/L for arsenic and 30 µg/L for uranium. Here, we evaluate the association between drinking water arsenic and uranium levels in three tribal regions in North Dakota and South Dakota participating in the Strong Heart Water Study. METHODS: Well water samples were collected in 2014-2020. Metal concentrations from 441 wells were dichotomized by their MCL for a graduated visualization across the regions. Spearman correlations and region-specific semivariograms were computed. Spatial interpolation using inverse distance weighting was conducted by region. RESULTS:Groundwater contamination was extensive; 29% and 7% of wells exceeded maximum contaminant levels for arsenic and uranium respectively. 81% of wells had both arsenic and uranium concentrations at one-tenth of their human-health benchmark (arsenic, 1 μg/L; uranium 3 μg/L). Well arsenic and uranium concentrations were uncorrelated (rs=0.06); however, there appeared to be a spatial correlation of wells co-contaminated by arsenic and uranium associated with flow along a geologic contact. CONCLUSIONS:Elevated arsenic and uranium in drinking water are common across Northern Plains Tribal Lands in the US. More than a third of all wells sampled contained either arsenic or uranium at levels exceeding the MCL, but co-contamination was more common in Region 3. These findings indicate the importance of measuring multiple metals in well water, and to understand underlying hydrogeological conditions. The underlying mechanisms for the prevalence of arsenic and uranium across Northern Plains Tribal Lands in the US, and in particular the occurrence of both elevated arsenic and uranium in drinking water wells in this region, demands further study. KEYWORDS: water quality, multi-pollutant, environmental disparities

Spatial relationship between well water arsenic and uranium in Northern Plains native lands

Arsenic and uranium in unregulated private wells affect many rural populations across the US. The distribution of these contaminants in the private wells of most American Indian communities is poorly characterized, and seldom studied together. Here, we evaluate the association between drinking water arsenic and uranium levels in wells (n = 441) from three tribal regions in North Dakota and South Dakota participating in the Strong Heart Water Study. Groundwater contamination was extensive; 29% and 7% of wells exceeded maximum contaminant levels for arsenic and uranium respectively. 81% of wells had both arsenic and uranium concentrations at one-tenth of their human-health benchmark (arsenic, 1 μg/L; uranium 3 μg/L). Well arsenic and uranium concentrations were uncorrelated (rs = 0.06); however, there appeared to be a spatial correlation of wells co-contaminated by arsenic and uranium associated with flow along a geologic contact. These findings indicate the importance of measuring multiple metals in well water, and to understand underlying hydrogeological conditions. The underlying mechanisms for the prevalence of arsenic and uranium across Northern Plains Tribal Lands in the US, and in particular the occurrence of both elevated arsenic and uranium in drinking water wells in this region, demands further study.

Prenatal Co-Exposure to Methylmercury and Inorganic Arsenic

Background/Aim: In the human body, arsenite is transported into cells through membrane channel proteins (i.e., aquaporins), while mercury decreases the permeability of aquaporins by binding to thiol groups. Thus exposure to mercury (through fish ingestion) may affect the metabolism of arsenite. This pilot study is focused on pregnant mothers, because the fetal period is considered the most vulnerable exposure window for methylmercury and arsenic.Methods: In 2019, 45 healthy pregnant mothers (&lt;21 weeks gestation) were enrolled at a hospital in Eugene, Oregon. After providing written informed consent, biomarkers were collected (blood, urine and hair samples). Blood methylmercury concentrations were determined, while arsenic species were analyzed in urine [inorganic arsenic, dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA)]. A tap water sample was brought from home for analysis of arsenic. We investigated unadjusted associations between blood methylmercury and urine arsenic species [%MMA (of total arsenic) and %DMA (of total arsenic)].Preliminary Results: All tap water arsenic concentrations were below the detection level (&lt;2 ppb); however the sum of urine arsenic species (= inorganic As + DMA + MMA) averaged 3.0 ppb (median: 2.5 ppb, range: 0.31-11 ppb, unadjusted for specific gravity). These values were comparable to other cohorts of pregnant mothers in the U.S. and Europe, where drinking water arsenic levels were low. Urine %MMA (of total arsenic) was inversely correlated with log10 blood methylmercury (Pearson's r: -0.25, p=0.12), while urine %DMA (of total arsenic) was positively correlated with log10 blood methylmercury (Pearson's r: 0.15, p=0.35).Conclusions: Although trends were non-significant, associations between urine arsenic species and blood methylmercury were suggestive. Analyses of specific aquaporins are ongoing, which may provide insight into these preliminary findings.

Arsenic exposure is associated with significant upper tract urothelial carcinoma health care needs and elevated mortality rates

PurposeThe aim of the study was to assess upper tract urothelial carcinoma (UTUC) health care needs and specific mortality rates in an arsenic-exposed region in Northern Chile and compare them to those of the rest of the country. Material and methodsArsenic levels of drinking water were correlated with UTUC hospital discharges and cancer-specific mortality rates. Mortality and hospital admission rate ratios were estimated using a Poisson regression model. ResultsThere were 257 UTUC-specific deaths in Chile between 1990 and 2016; 81 (34%) of them occurred in Antofagasta, where only 3.5% of the population lives. The peak mortality rate observed in Antofagasta was 2.15/100,000 compared to 0.07/100,000 in the rest of the country. Mortality in the exposed region was significantly higher when compared to the rest of the country (MRR 17.6; 95%CI: 13.5–22.9). The same trend was observed for UTUC hospital discharges (RR 14.8; 95%CI: 11.5–19.1). ConclusionEven stronger than for bladder cancer, exposure to arsenic is related to a significant need for UTUC health care and high mortality rates, even 25 years after having controlled arsenic levels in drinking-water. Awareness of this ecologic factor in these affected regions is therefore mandatory.

Higher risk of hyperglycemia with greater susceptibility in females in chronic arsenic-exposed individuals in Bangladesh

Arsenic (As) toxicity and diabetes mellitus (DM) are emerging public health concerns worldwide. Although exposure to high levels of As has been associated with DM, whether there is also an association between low and moderate As exposure and DM remains unclear. We explored the dose-dependent association between As exposure levels and hyperglycemia, with special consideration of the impact of demographic variables, in 641 subjects from rural Bangladesh. The total study participants were divided into three groups depending on their levels of exposure to As in drinking water (low, moderate and high exposure groups). Prevalence of hyperglycemia, including impaired glucose tolerance (IGT) and DM was significantly associated with the subjects' drinking water arsenic levels. Almost all exposure metrics (As levels in the subjects' drinking water, hair and nails) showed dose-dependent associations with the risk of hyperglycemia, IGT and DM. Among the variables considered, sex, age, and BMI were found to be associated with higher risk of hyperglycemia, IGT and DM. In sex-stratified analyses, As exposure showed a clearer pattern of dose-dependent risk for hyperglycemia in females than males. Finally, drinking water containing low-to-moderate levels of As (50.01–150 μg/L) was found to confer a greater risk of hyperglycemia than safe drinking water (As ≤10 μg/L). Thus the results suggested that As exposure was dose-dependently associated with hyperglycemia, especially in females.

Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009⁻2013)-A Negative Association.

While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 μg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of <50 μg/L, the historical limit for both the EPA and WHO. Data sources used included USGS for arsenic exposure, NCI for lung cancer outcome, and CDC and US Census Bureau forcovariates. Poisson log-linear models were conducted for male, female, and total populations using for exposure median county arsenic level, maximum arsenic level ≤50 μg/L, and ≥80% population groundwater dependency. Statistically significant negative associations were found in each of the six models in which the exposure was limited to those who had major exposure (≥80% dependency) to low-levels of arsenic (≤50 μg/L). This is the first large ecological study of lung cancer risk from drinking water arsenic levels that specifically examined the dose-response slope for populations whose exposure was below the historical limit of ≤50 μg/L. The models for each of the three populations (total; male; female) demonstrated an association that is both negative and statistically significant.

Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada

Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations—0–2μg/L; 2–5μg/L and; ≥5μg/L of arsenic—in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2–5μg/L) and 18% (≥5μg/L) greater than that of the referent group (<2μg/L), with posterior probabilities of 88% and 93% for these risks being above 1. Effect sizes for kidney cancer were 5% (2–5μg/L) and 14% (≥5μg/L) above that of the referent group (<2μg/L), with probabilities of 61% and 84%. High-risk areas were common in southwestern areas, where higher arsenic-levels are associated with the local geology. The study suggests an increased bladder cancer, and potentially kidney cancer, risk from exposure to drinking water arsenic-levels within the current the World Health Organization maximum acceptable concentration.

Arsenic in Drinking Water and Lung Cancer Mortality in the United States: An Analysis Based on US Counties and 30 Years of Observation (1950–1979)

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10–934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3–59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range of 3–59 µg/L. The upper-bound estimates of the risks are lower than the risks predicted from the SW Taiwan data and do not support those predictions. These results are consistent with a recent metaregression that indicated no increased lung cancer risk for arsenic exposures below 100–150 µg/L.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30years of epidemiological evidence.

BackgroundArsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework.MethodsForty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size.ResultsTwenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2–4.1]; 4.2 [2.1–6.3] and; 5.8 [2.9–8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35–4.0], 2.3 [0.59–6.4], and 3.1 [0.80–8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L.ConclusionArsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

Relationship between drinking water and toenail arsenic concentrations among a cohort of Nova Scotians

Consumption of arsenic-contaminated drinking water is associated with increased cancer risk. The relationship between arsenic body burden, such as concentrations in human toenails, and arsenic in drinking water is not fully understood. We evaluated the relationship between arsenic concentrations in drinking water and toenail clippings among a cohort of Nova Scotians. A total of 960 men and women aged 35 to 69 years provided home drinking water and toenail clipping samples. Information on water source and treatment use and covariables was collected through questionnaires. Arsenic concentrations in drinking water and toenail clippings and anthropometric indices were measured. Private drilled water wells had higher arsenic concentrations compared with other dug wells and municipal drinking water sources (P<0.001). Among participants with drinking water arsenic levels ≥1 μg/l, there was a significant relationship between drinking water and toenail arsenic concentrations (r=0.46, P<0.0001). Given similar levels of arsenic exposure from drinking water, obese individuals had significantly lower concentrations of arsenic in toenails compared with those with a normal weight. Private drilled water wells were an important source of arsenic exposure in the study population. Body weight modifies the relationship between drinking water arsenic exposure and toenail arsenic concentrations.

Comparison of Individual-level and Ecologic Studies of the Association of Drinking Water Contaminants on Adverse Birth Outcomes

Background Several epidemiological studies of the effects of drinking water contaminants have used ecologic designs, comparing groups defined by the community water system that they use. While ecologic studies are subject to bias, the degree of bias has rarely been assessed. Aims The aim of this analysis was to assess the bias from the use of ecologic study designs by comparing results from an individual-level study and an ecologic study of the association of arsenic in drinking water to adverse birth outcomes. Methods Maternal addresses at time of delivery were geocoded for over 651,000 live births (1989–2006) in the state of Utah, USA. Annual average arsenic levels were estimated for 476 Community Water Systems using water quality monitoring data. Arsenic levels were assigned to each birth by linking geocoded addresses to georeferenced water system service areas. Logistic regression was used to estimate the associations between individual arsenic levels and the occurrence of low birth weight (LBW), small for gestation age (SGA), pre-term and very preterm birth. For the ecologic study negative binomial regression was used to assess the relationship between annual average arsenic levels for each community water system and the proportion of births that were LBW, SGA, pre-term or very pre-term. Results There were significant associations between arsenic levels and the risk of LBW and SGA in both the individual-level and ecologic studies. Drinking water arsenic levels of 5 to &lt;10 µg/L were associated with LBW in the individual-level study (aOR=1.18; 95% CI 1.06, 1.32) and in the ecologic study (IRR=1.09; 95% CI 1.00, 1.19). There were no significant associations with pre-term or very pre-term in either analysis. Conclusions Results from the ecologic study were comparable with results from an individual-level study of the effects of arsenic on LBW and SGA. This work was supported by the Centers for Disease Control and Prevention, National Environmental Public Health Tracking Program (contract number 200-2010-37353).

Environmental justice implications of arsenic contamination in California’s San Joaquin Valley: a cross-sectional, cluster-design examining exposure and compliance in community drinking water systems

BackgroundFew studies of environmental justice examine inequities in drinking water contamination. Those studies that have done so usually analyze either disparities in exposure/harm or inequitable implementation of environmental policies. The US EPA’s 2001 Revised Arsenic Rule, which tightened the drinking water standard for arsenic from 50 μg/L to 10 μg/L, offers an opportunity to analyze both aspects of environmental justice.MethodsWe hypothesized that Community Water Systems (CWSs) serving a higher proportion of minority residents or residents of lower socioeconomic status (SES) have higher drinking water arsenic levels and higher odds of non-compliance with the revised standard. Using water quality sampling data for arsenic and maximum contaminant level (MCL) violation data for 464 CWSs actively operating from 2005–2007 in California’s San Joaquin Valley we ran bivariate tests and linear regression models.ResultsHigher home ownership rate was associated with lower arsenic levels (ß-coefficient= −0.27 μg As/L, 95% (CI), -0.5, -0.05). This relationship was stronger in smaller systems (ß-coefficient= −0.43, CI, -0.84, -0.03). CWSs with higher rates of homeownership had lower odds of receiving an MCL violation (OR, 0.33; 95% CI, 0.16, 0.67); those serving higher percentages of minorities had higher odds (OR, 2.6; 95% CI, 1.2, 5.4) of an MCL violation.ConclusionsWe found that higher arsenic levels and higher odds of receiving an MCL violation were most common in CWSs serving predominantly socio-economically disadvantaged communities. Our findings suggest that communities with greater proportions of low SES residents not only face disproportionate arsenic exposures, but unequal MCL compliance challenges.

75 ARSENIC EXPOSURE IS ASSOCIATED WITH SIGNIFICANT UPPER UROTHELIAL TRACT CANCER HEALTH CARE NEEDS AND ELEVATED MORTALITY RATES

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Evidence-based Medicine & Outcomes II1 Apr 201275 ARSENIC EXPOSURE IS ASSOCIATED WITH SIGNIFICANT UPPER UROTHELIAL TRACT CANCER HEALTH CARE NEEDS AND ELEVATED MORTALITY RATES Francisco Lopez, Mario Fernandez, and Fernando Coz Francisco LopezFrancisco Lopez Santiago, Chile More articles by this author , Mario FernandezMario Fernandez Santiago, Chile More articles by this author , and Fernando CozFernando Coz Santiago, Chile More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.121AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Upper tract urothelial cancer (UTUC) is a rare malignant disease with few known environmental risk factors. In particular, arsenic has not been clearly associated to higher UTUC incidence or mortality rates. Antofagasta is a well-known arsenic-exposed region in Northern Chile, with a significant impact of this geologic factor on public health, even two decades after having controlled arsenic concentrations in drinking-water. The aim of the study was to assess UTUC health care needs and mortality rates in this affected region during the last decades, comparing them to those of the rest of the country. METHODS Arsenic levels of drinking water of the affected region were obtained for the last 60 years and correlated with UTUC hospital discharges and mortality rates. Incident rate ratios and trends in mortality and hospital admission rates were estimated using a Poisson regression model, being the response variable the number of observed deaths in each age group for each year for Antofagasta and the rest of Chile. Separate calculations were made for men and women. RESULTS UTUC hospital discharges were significantly higher in the affected region (peak RR 5.5; 95%CI: 4.1 - 7.3). There were 220 UTUC-specific deaths in Chile between 1983 and 2009; 74 (34%) of them occurred in Antofagasta, where only 3.5% of the Chilean population lives. Mortality rates for UTUC were higher in this region during the analyzed period, reaching peak mortality rates of 79.2/100,000 in men and 33.2/100,000 in women. Poisson regression models showed increased mortality risk in the studied region compared to the rest of the country until present time for men (IRR 21.7; 95%CI: 15.4 - 30.7) and women (IRR 16.9; 95%CI: 10.4 - 27.5). Age at time of cancer-specific death was significantly lower in the exposed region than in the rest of the country (mean age 61.5; 95%CI: 58.9 - 63.9 vs. mean age 69.5; 95% CI: 67.7- 71.2; p<0.001). CONCLUSIONS Similar to bladder cancer, exposure to arsenic is clearly related to a significant need for UTUC health care and high mortality rates, even twenty years after having controlled arsenic levels in drinking-water. Affected populations should be aware of the significant impact of this ecologic factor and urologists should play an important role in defining strategies for early detection and management of UTUC in these exposed individuals. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e32 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francisco Lopez Santiago, Chile More articles by this author Mario Fernandez Santiago, Chile More articles by this author Fernando Coz Santiago, Chile More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population.

BackgroundArsenic 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 μg/L in the northeastern, western, and north central regions of the United States.ObjectivesWe investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression.MethodsWe 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.ResultsThe 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.ConclusionsThese 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.

Arsenic in Drinking-Water and Risk for Cancer in Denmark

BackgroundArsenic 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.ObjectiveOur aim was to determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer.MethodsThe 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 μg/L (mean = 1.2 μg/L). Cox’s regression models were used to analyze possible relationships between arsenic and cancer.ResultsWe 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/μg/L average exposure; 95% confidence interval, 0.84–0.94). Results adjusted for enrollment area showed no association with non-melanoma skin cancer.ConclusionsThe results indicate that exposure to low doses of arsenic might be associated with a reduced risk for skin cancer.

Maternal Arsenic Exposure Associated With Low Birth Weight in Bangladesh

To characterize the effects of maternal arsenic exposure on birth weight. Hair, toenail, and drinking water samples were collected from pregnant women (n = 52) at multiple time points during pregnancy and from their newborns after birth. Total arsenic was measured using inductively coupled plasma-mass spectrometry. The association between arsenic and birth weight was investigated using linear and logistic regression models. Maternal hair arsenic measured early in pregnancy was associated with decreased birth weight (beta = -193.5 +/- 90.0 g, P = 0.04). Maternal hair and drinking water arsenic levels measured at first prenatal visit were significantly correlated with newborn hair arsenic level (rho = 0.32, P = 0.04 and rho = 0.31, P = 0.04). Results suggest that maternal arsenic exposure early in pregnancy negatively affects newborn birth weight and that maternal hair provides the best integrated measure of arsenic exposure.

Inorganic Arsenic in Drinking Water: An Evolving Public Health Concern

In recent years, ingestion of inorganic arsenic from drinking water has emerged as an important scientific issue and public health concern. The International Agency for Research on Cancer has identified sufficient evidence in humans that inorganic arsenic causes lung, bladder, and nonmelanoma skin cancers ( 1 ) (summary at http://monographs.iarc.fr/ ). Reports by expert committees have suggested associations with several other cancer and noncancer outcomes ( 2 – 4 ). As a result, the US Environmental Protection Agency lowered the maximum contaminant level for arsenic in drinking water supplied by community water systems from 50 µ g/L, a level set in 1942, to 10 µ g/L, effective from January 2006. The reduction will necessitate changes to water systems serving approximately 13 million people ( http://www.epa.gov/safewater/arsenic/compliance. html ). The World Health Organization has similarly recommended 10 µ g/L for arsenic in water as a “guideline value” for setting national standards ( http://www.who.int/mediacentre/factsheets/fs210/en/ index.html ). Substantial numbers of people worldwide are exposed to elevated concentrations of arsenic. An estimated 25 million people in Bangladesh (19% of the population) and 6 million people in West Bengal, India (8% of the population), consume water with arsenic exceeding 50 µ g/L ( 5 ), with perhaps twice these numbers in these countries consuming water with arsenic levels exceeding 10 µ g/L. High levels of inorganic arsenic levels are found in drinking water in many other parts of the world, including areas of Argentina (county means ranged to 178 µ g/L) ( 6 ), the Inner Mongolia and Xinjiang autonomous regions in China (levels in excess of 600 µ g/L) ( 7 ), Finland (levels were generally low but ranged to 64 µ g/L) ( 8 ), northern Mexico (ranges in exposed areas to 160 – 740 µ g/L) ( 9 ), and the United States (with some areas in California, Nevada, Alaska, Michigan, New England, New Mexico, and Utah exceeding 50 µ g/L) (see US Geological Survey map of 31 350 ground water measurements at http://co.water.usgs.gov/trace/ pubs/arsenic_fi g1.html ). Drinking water arsenic levels in excess of 150 µ g/L also occur in Nepal ( 10 ), Thailand ( 11 ), Vietnam ( 12 ), Hungary ( 13 ), Ghana ( 14 ), and elsewhere ( 15 ). Although arsenic contamination of water supplies arises mainly from natural sources, human activities such as mining and ore processing may also contribute to elevated arsenic levels in some areas. Although ingestion of high levels of inorganic arsenic is most strongly linked to lung, bladder, and nonmelanoma skin cancers, there is evidence for associations with cancers of the kidney, liver, and possibly prostate ( 16 ). In addition, high levels of drinking water arsenic have been linked to cutaneous effects (hyperpigmentation, hypopigmentation, palmar – plantar hyperkeratoses, and leucomelanosis), gastrointestinal effects (gastrointestinal distress and liver cirrhosis), vascular effects (peripheral vascular diseases, such as blackfoot disease and Raynaud’s syndrome; arterial occlusions; cardiovascular disease; cerebrovascular disease; and hypertension), diabetes mellitus, and peripheral neuropathy ( 2 ), as well as to chronic cough, shortness of breath, and other respiratory effects ( 17 ). Arsenic can cross the placental barrier, and ingestion of high levels by pregnant women may cause adverse reproductive and developmental effects and increase rates of stillbirths, spontaneous abortions, low – birth weight deliveries, and neonatal and postneonatal mortality ( 18 , 19 ). Many of these associations were identifi ed from ecologic studies conducted in a limited number of populations; there have been relatively few analytic studies. Thus, many of the associations between arsenic ingestion and cancers other than lung, bladder, and nonmelanoma skin cancers and noncancer outcomes have not been conclusively demonstrated, and additional studies are needed. In this issue of the Journal, Marshall et al. ( 20 ) analyzed 50 years of mortality data for lung and bladder cancers, substantially extending a previous analysis ( 21 ). Data are ecologic and come from the climatologically and geologically unique setting of Region II in northern Chile. The climate is extremely arid, and the population lives primarily in cities and towns and relies almost exclusively on municipally supplied drinking water. Based on arsenic measurements made since the 1950s, arsenic levels within Region II have varied spatially and temporally, from highs of

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 microg/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 case-control 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, 25-40% 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 multiple measurements is unlikely to affect exposure classification of individuals into high- or low-exposure groups; however, collection of multiple samples may be advantageous for more refined exposure classification.