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.     

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.     

Evaluation of exposure to arsenic in residential soil

In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89-17.7 microg/L, respectively) and older participants (3.8, 1.9, 0.91-19.9 microg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background.     

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.     

Childhood cancer incidence and arsenic exposure in drinking water in Nevada

Inorganic arsenic exposure through drinking water causes cancer in adults; however, the carcinogenic potential in children remains unknown. A recent leukemia cluster in Churchill County, Nevada, where arsenic levels in water supplies are relatively high, has prompted concern. The authors investigated the incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties, grouped by low (i.e., < 10 microg/l), medium (10-25 microg/l), and high (35-90 microg/l) population-weighted arsenic levels in public drinking water supplies. The standardized incidence ratios (SIRs) for all childhood cancers combined were 1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and 1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties, respectively. There was no relationship between arsenic levels in water and childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90, 1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers, excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI = 0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old children and 10- to 14-yr-old children was in bone cancers, and the excess in 15- to 19-yr-old young adults was primarily in lymphomas. The findings in this study are reassuring in that leukemia risks were not increased at the concentrations of arsenic in water found in this study. Nonetheless, the results raise the possibility that there are increased risks for nonleukemic childhood cancers that require confirmation in other studies, particularly those in which higher exposures are addressed.     

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。     

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 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.     

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.     

Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE

There appears to be very good epidemiological evidence for a relationship between chlorination by-products, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers, including colorectal cancer appears to be inconclusive and inconsistent. There appears to be some evidence for a relationship between chlorination by-products, as measured by THMs, and small for gestational age (SGA)/intrauterine growth retardation (IUGR) and preterm delivery, but evidence for other outcomes such as low birth weight (LBW), stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent.     

The prevalence of subjective symptoms after exposure to arsenic in drinking water in Inner Mongolia,China

BACKGROUND: In Inner Mongolia, China, more than 300,000 people are chronically exposed to arsenic via their drinking water. We have previously reported that the prevalence of arsenical dermatosis was as high as 40% in the Hetao Plain area. However, the association between exposure to arsenic in drinking water and adverse health effects has not been fully examined. The purpose of this study was to examine the association between exposure to arsenic and prevalence of subjective symptoms. METHODS: A cross-sectional study was carried out in 431 residents of an arsenic-affected village and 189 residents of an arsenic-free village in 1996. Health-related interviews and physical examinations were conducted. The odds ratio for each subjective symptom was estimated, comparing residents of arsenic-free and affected villages. RESULTS: An arsenic level of 50+ microg/L was found in 90.6% of wells in the arsenic-affected village. Adjusted odds ratios of subjective symptoms, including coughs (odds ratio [OR] = 12.8, 95% confidence interval [CI]: 6.4-25.6), stomachaches (OR = 5.8, 95% CI: 3.6-9.4), palpitations (OR = 3.6, 95% CI: 1.5-8.2), urination problems (OR = 14.7, 95% CI: 3.3-65.5) and spontaneous abortions (OR = 2.7, 95% CI: 0.8-8.4), were markedly higher amongst residents of the arsenic-affected village, including those without arsenic dermatosis. CONCLUSIONS: The present study shows a high prevalence of subjective symptoms amongst residents of an arsenic-affected village. Symptoms occurred in people with and without arsenic dermatosis. Our findings suggest that symptoms other than dermatosis should be considered when a clinical diagnosis of arsenic toxicosis is made.     

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.     

Human exposure to trihalomethanes in drinking water]

Halogenated hydrocarbon compounds, some of them recognized as carcinogenic to different animal species can be found in drinking water. Chloroform, bromodichloromethane, dibromochloromethane and bromoform are the most important trihalomethanes found in potable water. They are produced in natural waters during chlorinated desinfection by the halogenation of precursors, specially humic and fulvic compounds. The review, in the MEDLINE covers the period from 1974 to 1998, presents the general aspects of the formation of trihalomethanes, sources of human exposure and their toxicological meaning for exposed organisms: toxicokinetic disposition and spectrum of toxic effects (carcinogenic, mutagenic and teratogenic).     

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.     

Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings

Purpose  

Evidence suggests that arsenic in drinking water causes non-malignant lung disease, but nearly all data concern exposed adults. The desert city of Antofagasta (population 257,976) in northern Chile had high concentrations of arsenic in drinking water (>800 μg/l) from 1958 until 1970, when a new treatment plant was installed. This scenario, with its large population, distinct period of high exposure, and accurate data on past exposure, is virtually unprecedented in environmental epidemiology. We conducted a pilot study on early-life arsenic exposure and long-term lung function. We present these preliminary findings because of the magnitude of the effects observed.     

Public exposure to 226Ra in drinking water

This paper presents a new method for calculating the effective dose of 226Ra regularly ingested with drinking water over a long period of time. The method is based on the assessment of cumulated 226Ra activity in the fraction retained in the whole body at time t (in days) after intake [so called m(t) value]. For modelling, simulation, and visualisation of the continuous intake of 226Ra by drinking water, we used the Simulink program package integrated with the Matlab. The dose assessment was performed for 226Ra activities of 5 mBq L(-1), 50 mBq L(-1), 1000 mBq L(-1) and 5000 mBq L(-1). The results suggest that 226Ra activities above 1000 mBq L(-1) produce effective doses which are below the recommended maximum. However, the potential effect of 226Ra activities of this extent is still unknown in children.     

Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown ; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action.