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There is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000–2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color. Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

BackgroundChronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). The contribution of water to total exposure is assumed to be low when water As and U concentrations are low.ObjectiveWe examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban U.S. communities.MethodsWe assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1485 and 6722 participants with dietary information and urinary biomarkers in the SHFS (2001–2003) and MESA (2000–2002; 2010–2011), respectively. Urine As was estimated as the sum of inorganic and methylated species, and urine U was total uranium. We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources via regression adjustment.ResultsThe median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a meta-analysis across both studies, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per twofold higher CWS As and U, respectively. In the SHFS, zip-code level factors such as private well and CWS As contributed 46% of variation in urine As, while in MESA, zip-code level factors, e.g., CWS As and U, contribute 30 and 49% of variation in urine As and U, respectively.Impact statementWe found that water from unregulated private wells and regulated CWSs is a major contributor to urinary As and U (an estimated measure of internal dose) in both rural, American Indian populations and urban, racially/ethnically diverse populations nationwide, even at levels below the current regulatory standard. Our findings indicate that additional drinking water interventions, regulations, and policies can have a major impact on reducing total exposures to As and U, which are linked to adverse health effects even at low levels.

Background: Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators. Methods: Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation. Results: Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HRperlog2=1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HRperlog2=1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype. Conclusions: Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation.

Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators. Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation. Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HR =1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HR =1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype. Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation. https://doi.org/10.1289/EHP16582.

Inorganic arsenic is a potent carcinogen and toxicant associated with numerous adverse health outcomes, and is number one on the Agency for Toxic Substances and Disease Registry Substance Priority List. Uranium is also a carcinogen and nephrotoxicant, however health effects at levels experienced by general populations is unclear. Chronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). Geogenic arsenic contamination typically occurs in groundwater as opposed to surface water supplies. Groundwater is a major source for many CWSs in the US. Although the US Environmental Protection Agency sets the maximum contaminant level (MCL enforceable since 2006: 10 µg/L) for arsenic in CWSs, private wells are not federally regulated. The contribution of drinking water from private wells and regulated CWSs to total inorganic arsenic and uranium exposure is not clear.In the United States (US), type 2 diabetes (T2D) affects approximately 37.3 million people (11.3% of the population), with the highest burden in American Indian communities. Toxic metal exposures have been identified as risk factors of T2D. Most studies rely on biomarkers, which could be affected by early disease processes. Studies directly measuring metals in drinking water in US populations have been limited.In Chapter 2, we evaluated county-level associations between modeled values of the probability of private well arsenic exceeding 10 µg/L and CWS arsenic concentrations for 2,231 counties in the conterminous US, using time invariant private well arsenic estimates and CWS arsenic estimates for two time periods. Nationwide, county-level CWS arsenic concentrations increased by 8.4 µg/L per 100% increase in the probability of private well arsenic exceeding 10 µg/L for 2006 – 2008 (the initial compliance monitoring period after MCL implementation), and by 7.3 µg/L for 2009 – 2011 (the second monitoring period following MCL implementation) (1.1 µg/L mean decline over time). Regional differences in this temporal decline suggest that interventions to implement the MCL were more pronounced in regions served primarily by groundwater. The strong association between private well and CWS arsenic in Rural, American Indian, and Semi Urban, Hispanic counties suggests that future research and regulatory support are needed to reduce water arsenic exposures in these vulnerable subpopulations. This comparison of arsenic exposure values from major private and public drinking water sources nationwide is critical to future assessments of drinking water arsenic exposure and health outcomes.In Chapter 3, we aimed to determine the association between drinking water arsenic estimates and urinary arsenic concentrations in the 2003-2014 National Health and Nutrition Examination Survey (NHANES). We evaluated 11,088 participants from the 2003-2014 NHANES cycles. For each participant, we assigned private well and CWS arsenic levels according to county of residence using estimates previously derived by the U.S. Environmental Protection Agency and U.S. Geological Survey. We used recalibrated urinary dimethylarsinate (rDMA) to reflect the internal dose of estimated water arsenic by applying a previously validated, residual-based method that removes the contribution of dietary arsenic sources. We compared the adjusted geometric mean ratios and corresponding percent change of urinary rDMA across tertiles of private well and CWS arsenic levels, with the lowest tertile as the reference. Comparisons were made overall and stratified by census region and race/ethnicity. Overall, the geometric mean of urinary rDMA was 2.52 (2.30, 2.77) µg/L among private well users and 2.64 (2.57, 2.72) µg/L among CWS users. Urinary rDMA was highest among participants in the West and South, and among Mexican American, Other Hispanic, and Non-Hispanic Other participants. Urinary rDMA levels were 25% (95% confidence interval (CI): 17-34%) and 20% (95% CI: 12-29%) higher comparing the highest to the lowest tertile of CWS and private well arsenic, respectively. The strongest associations between water arsenic and urinary rDMA were observed among participants in the South, West, and among Mexican American and Non-Hispanic White and Black participants. Both private wells and regulated CWSs are associated with inorganic arsenic internal dose as reflected in urine in the general U.S. population.In Chapter 4, our objective was to evaluate regional and sociodemographic inequalities in water arsenic exposure reductions associated with the US Environmental Protection Agency’s Final Arsenic Rule, which lowered the arsenic maximum contaminant level to 10 µg/L in public water systems. We analyzed 8,544 participants from the 2003-14 National Health and Nutrition Examination Survey (NHANES) reliant on community water systems (CWSs). We estimated arsenic exposure from water by recalibrating urinary dimethylarsinate (rDMA) to remove smoking and dietary contributions. We evaluated mean differences and corresponding percent reductions of urinary rDMA comparing subsequent survey cycles to 2003-04 (baseline), stratified by region, race/ethnicity, educational attainment, and tertile of CWS arsenic assigned at the county level. The overall difference (percent reduction) in urine rDMA was 0.32 µg/L (9%) among participants with the highest tertile of CWS arsenic, comparing 2013-14 to 2003-04. Declines in urinary rDMA were largest in regions with the highest water arsenic: the South [0.57 µg/L (16%)] and West [0.46 µg/L, (14%)]. Declines in urinary rDMA levels were significant and largest among Mexican American [0.99 µg/L (26%)] and Non-Hispanic White [0.25 µg/L (10%)] participants. Reductions in rDMA following the Final Arsenic Rule were highest among participants with the highest CWS arsenic concentrations, supporting legislation can benefit those who need it the most, although additional efforts are still needed to address remaining inequalities in CWS arsenic exposure.In Chapter 5, we examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban US communities. We assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1,485 and 6,722 participants with dietary information and urinary biomarkers in the SHFS (2001-2003) and MESA (2000-2002; 2010-2011), respectively. Total inorganic As exposure was estimated as the sum of inorganic and methylated species in urine (urine As). We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources of As and U via regression adjustment. The median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a mixed-effects meta-analysis of pooled effects across the SHFS and MESA, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per 2-fold higher CWS As and U, respectively. In the SHFS, CWS and private well As explained >40% of variability in urine As and CWS U explained >20% of urine U. In MESA, CWS As and U explained >50% of urine As and U. Water from public water supplies and private wells represents a major contributor to inorganic As and U exposure in diverse US populations.In Chapter 6, we examined the association of arsenic exposures in community water systems (CWS) and private wells with T2D incidence in the Strong Heart Family Study (SHFS), a prospective cohort of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban US communities, to evaluate direct associations between drinking water metal exposures and T2D risk. We evaluated adults in the SHFS free of T2D at baseline (2001-2003) and followed through 2010, with available private well and CWS arsenic (N=1,791) estimates assigned by residential zip code. We also evaluated adults in the MESA free of T2D at baseline (2000-2002) and followed through 2019, with available zip code level CWS arsenic (N=5,577) estimates. We used mixed effects Cox models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, body mass index (BMI), smoking status, and education. T2D incidence in the SHFS was 24.4 cases per 1,000 people (mean follow-up 5.6 years) and T2D incidence in MESA was 11.2 per 1,000 people (mean follow-up 6.0 years). In a meta-analysis of pooled effects across the SHFS and MESA, the corresponding hazard ratio (95% confidence interval) per 2-fold increase in water arsenic was 1.09 (1.01, 1.16). Differences were observed by BMI category and sex; positive associations were observed among participants with BMI <25 kg/m2 and among female participants. In categorical analyses, >10% probability of private well arsenic (<10% reference) in the SHFS and >1 µg/L of CWS arsenic (<1 µg/L reference) in MESA were associated with increased diabetes risk. Low to moderate water arsenic levels in unregulated private wells and federally regulated CWSs were associated with T2D incidence in the SHFS and MESA. In supplementary analyses, we also observed that CWS uranium was associated with T2D risk among SHFS and MESA participants with BMI<25 kg/m2.

Geocoding is a powerful tool for environmental exposure assessments that rely on spatial databases. Geocoding processes, locators, and reference datasets have improved over time; however, improvements have not been well-characterized. Enrollment addresses for the Agricultural Health Study, a cohort of pesticide applicators and their spouses in Iowa (IA) and North Carolina (NC), were geocoded in 2012–2016 and then again in 2019. We calculated distances between geocodes in the two periods. For a subset, we computed positional errors using “gold standard” rooftop coordinates (IA; N = 3566) or Global Positioning Systems (GPS) (IA and NC; N = 1258) and compared errors between periods. We used linear regression to model the change in positional error between time periods (improvement) by rural status and population density, and we used spatial relative risk functions to identify areas with significant improvement. Median improvement between time periods in IA was 41 m (interquartile range, IQR: −2 to 168) and 9 m (IQR: −80 to 133) based on rooftop coordinates and GPS, respectively. Median improvement in NC was 42 m (IQR: −1 to 109 m) based on GPS. Positional error was greater in rural and low-density areas compared to in towns and more densely populated areas. Areas of significant improvement in accuracy were identified and mapped across both states. Our findings underscore the importance of evaluating determinants and spatial distributions of errors in geocodes used in environmental epidemiology studies.