Hundreds of different disinfection byproducts form in drinking water following necessary treatment with chlorine and other disinfectants, and many of those byproducts can damage DNA and increase the risk of cancer. This study offers the first side-by-side comparison of cancer risk assessments based on toxicological and epidemiological studies of disinfection byproducts using a comprehensive contaminant occurrence dataset for haloacetic acids and trihalomethanes, two groups of disinfection byproducts that are regulated in drinking water. We also provide the first analysis of a new occurrence dataset for unregulated haloacetic acids that became available from the latest, fourth round of the U.S. EPA-mandated unregulated contaminant monitoring program (UCMR4). A toxicological assessment indicated that haloacetic acids, and in particular brominated haloacetic acids, are more carcinogenic and are associated with a greater number of attributable cancer cases than trihalomethanes. Based on the toxicological analysis, cumulative lifetime cancer risk due to exposure to trihalomethanes and haloacetic acids for community water systems monitored under UCMR4, estimated with standard default parameters for body weight and water intake, corresponds to 7.0 × 10⁻⁵ (3.5 × 10⁻⁵–1.3 × 10⁻⁴). The same analysis conducted with age sensitivity factors to account for elevated risk in infants and children yielded a cumulative risk estimate of 2.9 × 10⁻⁴ (1.7 × 10⁻⁴–6.2 × 10⁻⁴). Epidemiological data suggest that lifetime cancer risk from disinfection byproducts for the U.S. population served by community water systems is approximately 3.0 × 10⁻³ (2.1 × 10⁻⁴–5.7 × 10⁻³), or a lifetime cancer risk of three cases per thousand people. Overall, this analysis highlights the value of using human data in health risk assessments to the greatest extent possible.

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Research studies analyzing the geospatial distribution of air pollution and other types of environmental contamination documented the persistence of environmental health disparities between communities. Due to the shortage of publicly available data, only limited research has been published on the geospatial distribution of drinking water pollution. Here we present a framework for the joint consideration of community-level drinking water data and demographic data. Our analysis builds on a comprehensive data set of drinking water contaminant occurrence for the United States for 2014–2019 and the American Community Survey 5-year estimates (2015–2019) from the U.S. Census Bureau. Focusing on the U.S. states of California and Texas for which geospatial data on community water system service boundaries are publicly available, we examine cumulative cancer risk for water served by community water systems of different sizes relative to demographic characteristics for the populations served by these water systems. In both California and Texas, greater cumulative cancer risk was observed for water systems serving communities with a higher percentage of Hispanic/Latino and Black/African American community members. This investigation demonstrates that it is both practical and essential to incorporate and expand the drinking water data metrics in the analysis of environmental pollution and environmental health. The framework presented here can support the development of public policies to advance environmental health justice priorities on state and federal levels in the U.S.