Elevated prenatal methylmercury exposure in Nigeria: evidence from maternal and cord blood.

Methylmercury is a neurodevelopmental toxicant that is globally distributed though little is known about prenatal exposures in sub-Saharan Africa. The objective of the current study was to measure total mercury levels in cord blood and maternal blood from 95 mother-newborn pairs recruited from hospitals in Nnewi, Nigeria. The secondary aims of the study were to explore if demographic and dietary factors were associated with blood mercury levels, and to explore if mercury levels were associated with any self-reported health outcome and childbirth outcome. Maternal blood mercury levels averaged 3.6 µg L(-1) and ranged from 1.1 µg L(-1) to 9.5 µg L(-1). Cord blood mercury averaged 5.1 µg L(-1) and ranged from 1.2 µg L(-1) to 10.6 µg L(-1). The mean ratio of mercury in paired cord blood to maternal blood was 1.5 and it ranged from 0.4 to 3.2. Mercury in maternal and cord blood were significantly correlated (r=0.471). More than one-third of mothers reported eating fish at least once per day, and a weak (p=0.08) fish consumption-related increase in blood mercury was found. Cord blood mercury was positively and significantly associated with birth weight and length, and head and chest circumference. Mercury levels in 36% of the participants exceeded the biomonitoring guideline associated with the United States Environmental Protection Agency (U.S. EPA) reference dose for mercury. The study shows that pregnant women and their newborns are exposed to methylmercury and that their exposures are higher compared to general populations sampled from other regions of the world.

Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case-control study.

BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. METHODS: Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case-control study in Southeastern Michigan and exposed to low to moderate (<50 µg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. RESULTS: While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 µg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). CONCLUSIONS: Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 µg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1 µg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

Multiple metals exposure in a small-scale artisanal gold mining community.

Urinary metals were characterized in 57 male residents of a small-scale gold mining community in Ghana. Chromium and arsenic exceeded health guideline values for 52% and 34%, respectively, of all participants. About 10-40% of the participants had urinary levels of aluminum, copper, manganese, nickel, selenium, and zinc that fell outside the U.S. reference range. Exposures appear ubiquitous across the community as none of the elements were associated with occupation, age, and diet.

Lead poisoning and asthma among low-income and African American children in Saginaw, Michigan.

OBJECTIVE: We sought to ascertain whether asthmatic children are more likely to have elevated blood lead levels (EBLLs), BLLs ≥ 10 µg/dL, than non-asthmatic children. Household risk factors associated with both lead and asthma were examined. METHOD: We undertook a cross-sectional study involving children residing in mainly low-income and minority households in Michigan which were identified by the Statewide Systemic Tracking of Elevated Lead Levels and Remediation database (STELLAR) (n=356 children). RESULTS: Of the 356 index children, 19% had EBLLs and 15% were doctor-diagnosed asthmatic. After adjusting for confounders known to be related to lead poisoning and/or asthma, association remained between asthmatic children and EBLL children (AOR: 5.17; 95% CI (1.25-21.37)). CONCLUSIONS: The results of our study show that asthmatic children are over 5 times more likely to have EBLLs than non-asthmatics (AOR: 5.17; 95% CI (1.25-21.37)). Intervention strategies designed to address lead poisoning prevention may be effective in reducing incidence of asthma. Further study is required.

Low-level determination of six arsenic species in urine by High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry (HPLC-ICP-MS).

Many methods that have been used to speciate arsenic metabolites in urine are unable to adequately resolve the chromatographic peaks for arsenite (As[iii]) and arsenobetaine (AsB). We present a High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry (HPLC-ICP-MS) method that has been optimized to reliably measure the following six arsenic species in human urine: As[iii], arsenate (As[v]), monomethylarsonous acid (MMA[iii]), monomethylarsonic acid (MMA[v]), dimethylarsinic acid (DMA[v]) and AsB. The method was evaluated with regards to changes in mobile phase, accuracy and precision. The ability to quantify the six species in a given sample depended on the low detection limits of the method-0.06 µg L-1 for AsB, 0.11 µg L-1 for As[iii], 0.08 µg L-1 for DMA[v], 0.12 µg L-1 for MMA[v] and 0.15 µg L-1 for As[v]. The procedure was used to measure the six arsenic species in urine samples from 387 individuals in southeast Michigan who are chronically exposed to slightly elevated levels of arsenic in their drinking water. The DMA[v] was detected in 99.2% of samples, AsB in 98.2%, MMA[v] in 73.4%, As[iii] in 45.0%, and As[v] in 27.1%. No MMA[iii] was detected even in samples analyzed within 6 hours after collection. The results raise some doubt as to whether MMA[iii] is a significant metabolite in urine of people exposed to arsenic concentrations below 20 µg L-1 in their drinking water.

Incorporating individual-level distributions of exposure error in epidemiologic analyses: an example using arsenic in drinking water and bladder cancer.

PURPOSE: Epidemiologic analyses traditionally rely on point estimates of exposure for assessing risk despite exposure error. We present a strategy that produces a range of risk estimates reflecting distributions of individual-level exposure. METHODS: Quantitative estimates of exposure and its associated error are used to create for each individual a normal distribution of exposure estimates which is then sampled using Monte Carlo simulation. After the exposure estimate is sampled, the relationship between exposure and disease is evaluated; this process is repeated 99 times generating a distribution of risk estimates and confidence intervals. This is demonstrated in a bladder cancer case-control study using individual-level distributions of exposure to arsenic in drinking water. RESULTS: Sensitivity analyses indicate similar performance for categorical or continuous exposure estimates, and that increases in exposure error translate into a wider range of risk estimates. Bladder cancer analyses yield a wide range of possible risk estimates, allowing quantification of exposure error in the association between arsenic and bladder cancer, typically ignored in conventional analyses. CONCLUSIONS: Incorporating distributions of individual-level exposure error results in a more nuanced depiction of epidemiologic findings. This approach can be readily adopted by epidemiologists assuming distributions of individual-level exposure.

Reliability of spot urine samples in assessing arsenic exposure.

Urinary arsenic concentration is often used as a biomarker of arsenic exposure. First morning void (FMV) and spot urine samples from 131 participants in southeastern Michigan were analyzed using an HPLC-IC-PMS system for six different arsenic species: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsonous acid MMA[III], methylarsenic acid MMA[V], and dimethylarsenic DMA[V]. Bland-Altman plots, intraclass correlation coefficients (ICCs), and Pearson correlation procedures were used to evaluate the relationship between the arsenic species in FMV and spot urine collections after normalizing the samples by specific gravity. DMA[III] and MMA[III] were not detected in any of the samples. The sum of As[III], As[V], MMA[V], and DMA[V] was designated SumAs. The ICC between SumAs in FMV and SumAs in spot samples was 0.90. The ICC showed that 90% of variation comes from between individuals and not within individuals. A significant correlation (r=0.80 p<0.001) was observed between FMV and spot samples for SumAs. The spot sample were a good predictor of the MMA[V] (r=0.83 p<0.0001), and DMA[V] (r=0.77 p<0.0001) in the FMV sample. These associations suggest that either FMV or spot samples can be used as an adequate bioindicator of arsenic metabolites in human urine. The benefit of using spot urine samples, instead of 24-h or FMV urine samples, is the potential reduction in budgetary and logistic requirements in epidemiological studies.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USA.

OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure.

Influence of groundwater recharge and well characteristics on dissolved arsenic concentrations in southeastern Michigan groundwater.

Arsenic concentrations exceeding 10 microg/l, the United States maximum contaminant level and the World Health Organization guideline value, are frequently reported in groundwater from bedrock and unconsolidated aquifers of southeastern Michigan. Although arsenic-bearing minerals (including arsenian pyrite and oxide/hydroxide phases) have been identified in Marshall Sandstone bedrock of the Mississippian aquifer system and in tills of the unconsolidated aquifer system, mechanisms responsible for arsenic mobilization and subsequent transport in groundwater are equivocal. Recent evidence has begun to suggest that groundwater recharge and characteristics of well construction may affect arsenic mobilization and transport. Therefore, we investigated the relationship between dissolved arsenic concentrations, reported groundwater recharge rates, well construction characteristics, and geology in unconsolidated and bedrock aquifers. Results of multiple linear regression analyses indicate that arsenic contamination is more prevalent in bedrock wells that are cased in proximity to the bedrock-unconsolidated interface; no other factors were associated with arsenic contamination in water drawn from bedrock or unconsolidated aquifers. Conditions appropriate for arsenic mobilization may be found along the bedrock-unconsolidated interface, including changes in reduction/oxidation potential and enhanced biogeochemical activity because of differences between geologic strata. These results are valuable for understanding arsenic mobilization and guiding well construction practices in southeastern Michigan, and may also provide insights for other regions faced with groundwater arsenic contamination.

Effects of nutritional measures on toenail arsenic concentration as a biomarker of arsenic exposure.

Correlations between drinking water and toenail arsenic concentrations have been demonstrated in previous studies, yet factors that may modify the exposure-biomarker association have not been adequately assessed. Using data from 500 controls enrolled in a bladder cancer study underway in Michigan, USA, the effects of demographic characteristics and nutritional measures on the biomarker response were evaluated. Drinking water and toenail samples were collected during a home visit and analyzed for arsenic and other elements. Participants reported dietary supplement intake habits and provided demographic data. Arsenic concentrations of drinking water and toenail samples were positively correlated. Of the nutritional measures evaluated, toenail iron concentration was a significant modifier of the exposure-biomarker association. No demographic characteristics or general measures of dietary intake affected the biomarker response. The results presented herein are critical for biomarker validation and prove promising for sound application of the arsenic toenail biomarker to future epidemiological investigations.

Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon?

A case-control study was conducted to examine whether occupational or environmental exposures, particularly to heavy metals, are associated with male infertility in Lebanon, a war-torn country with a history of environmental degradation. Seventy-four infertile cases and 76 fertile controls were selected from 2 major fertility clinics in Beirut. Data collection involved risk-factor interviews, semen analysis, and blood collection for heavy metal analysis. Multiple regression analysis showed that men with reported occupational exposures were twice as likely to be infertile as unexposed men. However, none of the subcategories of infertile men (based on semen analysis results) had significantly higher whole blood concentrations of heavy metals when compared to fertile controls. Blood concentrations were well within the range for referent populations of healthy individuals. Thus, despite Lebanon's poor record of occupational and environmental stewardship, exposure to metal pollutants does not appear to represent an important risk factor for male infertility.

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.

Validity of spatial models of arsenic concentrations in private well water.

OBJECTIVE: Arsenic is a pervasive contaminant in underground aquifers worldwide, yet documentation of health effects associated with low-to-moderate concentrations (<100microg/L) has been stymied by uncertainties in assessing long-term exposure. A critical component of assessing exposure to arsenic in drinking water is the development of models for predicting arsenic concentrations in private well water in the past; however, these models are seldom validated. The objective of this paper is to validate alternative spatial models of arsenic concentrations in private well water in southeastern Michigan. METHODS: From 1993 to 2002, the Michigan Department of Environmental Quality analyzed arsenic concentrations in water from 6050 private wells. This dataset was used to develop several spatial models of arsenic concentrations in well water: proxy wells based on nearest-neighbor relationships, averages across geographic regions, and geostatistically derived estimates based on spatial correlation and geologic factors. Output from these models was validated using arsenic concentrations measured in 371 private wells from 2003 to 2006. RESULTS: The geostatisical model and nearest-neighbor approach outperformed the models based on geographic averages. The geostatistical model produced the highest degree of correlation using continuous data (Pearson's r=0.61; Spearman's rank rho=0.46) while the nearest-neighbor approach produced the strongest correlation (kappa(weighted)=0.58) using an a priori categorization of arsenic concentrations (<5, 5-9.99, 10-19.99, > or = 20microg/L). When the maximum contaminant level was used as a cut-off in a two-category classification (<10, > or =10microg/L), the nearest-neighbor approach and geostatistical model had similar values for sensitivity (0.62-0.63), specificity (0.80), negative predictive value (0.85), positive predictive value (0.53), and percent agreement (75%). DISCUSSION: This validation study reveals that geostatistical modeling and nearest-neighbor approaches are effective spatial models for predicting arsenic concentrations in private well water. Further validation analyses in other regions are necessary to indicate how widely these findings may be generalized.

WITHDRAWN: Book review.

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Determination of toxic and essential elements in children's blood with inductively coupled plasma-mass spectrometry.

Recent studies have suggested that low blood lead level, less than 50 microg L(-1), can influence the neurobehavioral performance of children. In addition, nutritional deficiencies in some essential elements may increase the toxicity of lead, and some essential elements may influence the blood concentrations of lead and other toxic metals. These findings, coupled with the scarcity of available data on some elements in children's blood and the introduction of methylcyclopentadienyl manganese tricarbonyl (MMT) to gasoline, accentuate the need to monitor the concentrations of lead, manganese, and other heavy metals and essential elements in children's blood. This study reports on the multi-element analysis of blood of South African school children using inductively coupled plasma-mass spectrometry (ICP-MS). The sample preparation consisted of a nitric acid/hydrogen peroxide open digestion and subsequent dilution with MilliQ water. The accuracy and precision were evaluated from quintuplet analyses of Seronorm trace elements whole blood reference material and human blood samples. Concentrations of lead, arsenic, manganese, copper, zinc, selenium, cobalt, and chromium in the blood of South African school children were determined. The average values were: lead 56.4 microg L(-1), arsenic 1.53 microg L(-1), manganese 8.48 microg L(-1), copper 1195 microg L(-1), zinc 3431 microg L(-1), selenium 176 microg L(-1), cobalt 0.80 microg L(-1), and chromium 1.25 microg L(-1). The level of lead was in line with some reported lower concentrations. The concentrations of arsenic and manganese were generally lower than those found in the literature. The concentrations of cobalt, copper, selenium, and chromium were higher than those found in other studies, whereas that of zinc was lower.

Toenails as a biomarker of inorganic arsenic intake from drinking water and foods.

Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure.

Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis.

BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 microg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10-100 microg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population-weighted mean arsenic concentration of 11.00 microg/L and a population-weighted median of 7.58 microg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09-1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14-1.25; F SMR, 1.19; CI, 1.15-1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18-1.37; F SMR, 1.27; CI, 1.19-1.35), and kidney diseases (M SMR, 1.28; CI, 1.15-1.42; F SMR, 1.38; CI, 1.25-1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis.

Individual lifetime exposure to inorganic arsenic using a space-time information system.

OBJECTIVES: A space-time information system (STIS) based method is introduced for calculating individual-level estimates of inorganic arsenic exposure over the adult life-course. STIS enables visualization and analysis of space-time data, overcoming some of the constraints inherent to spatial-only Geographic Information System software. The power of this new methodology is demonstrated using data from southeastern Michigan where 8% of the population is exposed to arsenic >10 microg/l (the World Health Organization guideline) in home drinking water. METHODS: Participants (N=440) are members of a control group in a population-based bladder cancer case-control study in southeastern Michigan and were recruited by phone using random digit dialing. Water samples were collected and analyzed for arsenic at current residence and participants were required to answer questions concerning lifetime mobility history and dietary habits. Inorganic arsenic concentrations were estimated at past residences and workplaces, and in select foods. Fluid and food consumption data were integrated with mobility histories and arsenic concentrations to calculate continuous estimates of inorganic arsenic intake over the adult life-course. RESULTS: Estimates of continuous arsenic exposure are displayed, making use of both participant age and calendar year as measures of time. Results illustrate considerable temporal variability in individual-level exposure, with 26% of the participants experiencing a change in drinking water arsenic concentration of at least +/-10 microg/l over their adult lives. The average cumulative intake over the adult life-course ranges from 2.53 x 10(4)-1.30 x 10(5) microg, depending on the selected exposure metric. CONCLUSIONS: The STIS-based exposure assessment method allows for flexible inclusion of different parameters or alternative formulations of those parameters, thus enabling the calculation of different exposure metrics. This flexibility is particularly useful when additional exposure routes are considered, input datasets are updated, or when a scientific consensus does not exist regarding the proper formulation of the exposure metric. These results demonstrate the potential of STIS as a useful tool for calculating continuous estimates of adult lifetime exposure to arsenic or other environmental contaminants for application in exposure and risk assessment.