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In this perspective, we evaluate key and emerging epidemiological and toxicological data concerning immunotoxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) and seek to reconcile conflicting conclusions from two reviews published in 2016. We summarize ways that immunosuppression and immunoenhancement are defined and explain how specific outcomes are used to evaluate immunotoxicity in humans and experimental animals. We observe that different approaches to defining immunotoxicological outcomes, particularly those that do not produce clinical disease, may lead to different conclusions from epidemiological and toxicological studies. The fundamental point that we make is that aspects of epidemiological studies considered as limitations can be minimized when data from toxicological studies support epidemiological findings. Taken together, we find that results of epidemiological studies, supported by findings from toxicological studies, provide strong evidence that humans exposed to PFOA and PFOS are at risk for immunosuppression.

Background Low-income and minority communities often face disproportionately high pollutant exposures. The lead crisis in Flint, Michigan, has sparked concern about broader socioeconomic disparities in exposures to drinking water contaminants. Nitrate is commonly found in drinking water, especially in agricultural regions, and epidemiological evidence suggests elevated risk of cancer and birth defects at levels below U.S. EPA’s drinking water standard (10 mg/L NO 3 -N). However, there have been no nationwide assessments of socioeconomic disparities in exposures to nitrate or other contaminants in U.S. drinking water. The goals of this study are to identify determinants of nitrate concentrations in U.S. community water systems (CWSs) and to evaluate disparities related to wealth or race/ethnicity. Methods We compiled nitrate data from 39,466 U.S. CWSs for 2010–2014. We used EPA’s Safe Drinking Water Information System (SDWIS) to compile CWS characteristics and linked this information with both city- and county-level demographic data gathered from the U.S. Census Bureau. After applying multiple imputation methods to address censored nitrate concentration data, we conducted mixed-effects multivariable regression analyses at national and regional scales. Results 5.6 million Americans are served by a CWS that had an average nitrate concentration ≥ 5 mg/L NO 3 -N between 2010 and 2014. Extent of agricultural land use and reliance on groundwater sources were significantly associated with nitrate. The percent of Hispanic residents served by each system was significantly associated with nitrate even after accounting for county-level cropland and livestock production, and CWSs in the top quartile of percent Hispanic residents exceeded 5 mg/L nearly three times as often as CWSs serving the lowest quartile. By contrast, the percent of residents living in poverty and percent African American residents were both inversely associated with nitrate. Conclusions Epidemiological evidence for health effects associated with drinking water above 5 mg/L NO 3 -N raises concerns about increased risk for the 5.6 million Americans served by public water supplies with average nitrate concentrations above this level. The associations we observed between nitrate concentrations and proportions of Hispanic residents support the need for improved efforts to assist vulnerable communities in addressing contamination and protecting source waters. Future studies can extend our methods to evaluate disparities in exposures to other contaminants and links to health effects.

BackgroundAdvances in drinking water infrastructure and treatment throughout the 20th and early 21st century dramatically improved water reliability and quality in the United States (US) and other parts of the world. However, numerous chemical contaminants from a range of anthropogenic and natural sources continue to pose chronic health concerns, even in countries with established drinking water regulations, such as the US.Objective/MethodsIn this review, we summarize exposure risk profiles and health effects for seven legacy and emerging drinking water contaminants or contaminant groups: arsenic, disinfection by-products, fracking-related substances, lead, nitrate, per- and polyfluorinated alkyl substances (PFAS) and uranium. We begin with an overview of US public water systems, and US and global drinking water regulation. We end with a summary of cross-cutting challenges that burden US drinking water systems: aging and deteriorated water infrastructure, vulnerabilities for children in school and childcare facilities, climate change, disparities in access to safe and reliable drinking water, uneven enforcement of drinking water standards, inadequate health assessments, large numbers of chemicals within a class, a preponderance of small water systems, and issues facing US Indigenous communities.ResultsResearch and data on US drinking water contamination show that exposure profiles, health risks, and water quality reliability issues vary widely across populations, geographically and by contaminant. Factors include water source, local and regional features, aging water infrastructure, industrial or commercial activities, and social determinants. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general problems, ascertaining the state of drinking water resources, and developing mitigation strategies.Impact statementDrinking water contamination is widespread, even in the US. Exposure risk profiles vary by contaminant. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general public health problems, ascertaining the state of drinking water resources, and developing mitigation strategies.

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of consumer products for their water- and grease-resistant properties, but few studies have explored this exposure route. We used multiple regression to investigate associations between six self-reported behaviors hypothesized to influence PFAS exposure and serum concentrations of six PFAS chemicals in 178 middle-aged women enrolled in the Child Health and Development Studies, about half of whom are African American. Blood samples were collected in 2010–2013, and participants were interviewed about behavior in 2015–2016. Results showed that African American women had lower levels of perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS) compared with non-Hispanic white women. In African Americans, but not others, frequent consumption of prepared food in coated cardboard containers was associated with higher levels of four PFASs. Flossing with Oral-B Glide, having stain-resistant carpet or furniture, and living in a city served by a PFAS-contaminated water supply were also associated with higher levels of some PFASs. Product testing using particle-induced γ-ray emission (PIGE) spectroscopy confirmed that Oral-B Glide and competitor flosses contained detectable fluorine. Despite the delay between blood collection and interview, these results strengthen the evidence for exposure to PFASs from food packaging and implicate exposure from polytetrafluoroethylene (PTFE)-based dental floss for the first time.

Per- and polyfluoroalkyl substances (PFASs) are common industrial and consumer product chemicals with widespread human exposures that have been linked to adverse health effects. PFASs are commonly detected in foods and food-contact materials (FCMs), including fast food packaging and microwave popcorn bags. Our goal was to investigate associations between serum PFASs and consumption of restaurant food and popcorn in a representative sample of Americans. We analyzed 2003-2014 serum PFAS and dietary recall data from the National Health and Nutrition Examination Survey (NHANES). We used multivariable linear regressions to investigate relationships between consumption of fast food, restaurant food, food eaten at home, and microwave popcorn and serum levels of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS). Calories of food eaten at home in the past 24 h had significant inverse associations with serum levels of all five PFASs; these associations were stronger in women. Consumption of meals from fast food/pizza restaurants and other restaurants was generally associated with higher serum PFAS concentrations, based on 24-h and 7-d recall, with limited statistical significance. Consumption of popcorn was associated with significantly higher serum levels of PFOA, PFNA, PFDA, and PFOS, based on 24-h and 12-month recall, up to a 63% (95% CI: 34, 99) increase in PFDA among those who ate popcorn daily over the last 12 months. Associations between serum PFAS and popcorn consumption may be a consequence of PFAS migration from microwave popcorn bags. Inverse associations between serum PFAS and food eaten at home-primarily from grocery stores-is consistent with less contact between home-prepared food and FCMs, some of which contain PFASs. The potential for FCMs to contribute to PFAS exposure, coupled with concerns about toxicity and persistence, support the use of alternatives to PFASs in FCMs. https://doi.org/10.1289/EHP4092.

Unregulated contaminants in drinking water, such as per- and polyfluoroalkyl substances (PFAS), can contribute to cumulative health risks, particularly in overburdened and less-advantaged communities. To our knowledge, there has been no nationwide assessment of socioeconomic disparities in exposures to unregulated contaminants in drinking water. The goals of this study were to identify determinants of unregulated contaminant detection among US public water systems (PWSs) and evaluate disparities related to race, ethnicity, and socioeconomic status. We gathered data from the US Environmental Protection Agency's (US EPA's) Third Unregulated Contaminant Monitoring Rule (2013-2015), PWS characteristics, sociodemographic data, and suspected pollution sources from regulatory databases. We included four target contaminants (or classes) with industrial sources: PFAS, 1,4-dioxane, 1,1-dichloroethane, and chlorodifluoromethane (HCFC-22). Associations were evaluated with pairwise comparison tests and generalized logistic mixed-effects regression models for six dichotomous outcomes: detection of each of four target contaminants, detection of target contaminant, and PWS exceedance of US EPA health reference level that was in effect in 2017. More than 97 million US residents were served by a PWS with detectable levels of 1,4-dioxane (22% of PWSs), HCFC-22 (5.8%), 1,1-dichloroethane (4.7%), and/or PFAS (4.0%). Unregulated contaminant detection was more frequent among large systems, urban systems, and systems using groundwater or a combination of groundwater and surface water. In comparison with PWSs with no detectable levels of these unregulated contaminants, PWSs with detectable levels served counties with higher proportions of Hispanic residents (17% vs. 13%), as did PWSs that exceeded EPA health reference levels in comparison with PWSs with no exceedances (18% vs. 14%). There were persistent positive associations between proportions of Hispanic residents and detections of target contaminants, even after accounting for pollution sources. Previously, inequities in exposures to drinking water contaminants were underestimated because prior studies have focused on regulated contaminants. PWSs serving counties with more Hispanic residents, non-Hispanic Black residents, and urban households may benefit from additional resources to proactively mitigate unregulated chemical contamination. Future studies should evaluate factors underlying these disparities to promote actions that protect water quality for all residents. https://doi.org/10.1289/EHP14721.

Communities across the U.S. are discovering drinking water contaminated by perfluoroalkyl and polyfluoroalkyl substances (PFAS) and determining appropriate actions. There are currently no federal PFAS drinking water standards despite widespread drinking water contamination, ubiquitous population-level exposure, and toxicological and epidemiological evidence of adverse health effects. Absent federal PFAS standards, multiple U.S. states have developed their own health-based water guideline levels to guide decisions about contaminated site cleanup and drinking water surveillance and treatment. We examined perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) water guideline levels developed by the U.S. Environmental Protection Agency (EPA) and state agencies to protect people drinking the water, and summarized how and why these levels differ. We referenced documents and tables released in June 2018 by the Interstate Technology and Regulatory Council (ITRC) to identify states that have drinking water and groundwater guideline levels for PFOA and/or PFOS that differ from EPA’s health advisories (HAs). We also gathered assessment documents from state websites and contacted state environmental and health agencies to identify and confirm current guidelines. Seven states have developed their own water guideline levels for PFOA and/or PFOS ranging from 13 to 1000 ng/L, compared to EPA’s HA of 70 ng/L for both compounds individually or combined. We find that the development of PFAS guideline levels via exposure and hazard assessment decisions is influenced by multiple scientific, technical, and social factors, including managing scientific uncertainty, technical decisions and capacity, and social, political, and economic influences from involved stakeholders. Assessments by multiple states and academic scientists suggest that EPA’s HA is not sufficiently protective. The ability of states to develop their own guideline levels and standards provides diverse risk assessment approaches as models for other state and federal regulators, while a sufficiently protective, scientifically sound, and enforceable federal standard would provide more consistent protection.

Infant exposures to metals are a concern for mining-impacted communities, although limited information is available to assess residential exposures over the first year of life. We measured lead (Pb), manganese, arsenic, and cadmium in indoor air, house dust, yard soil, and tap water from 53 infants’ homes near the Tar Creek Superfund Site (Oklahoma, USA) at two time points representing developmental stages before and during initial ambulation (age 0–6 and 6–12 months). We measured infant metal biomarkers in: umbilical cord blood ( n =53); 12- ( n =43) and 24- ( n =22) month blood; and hair at age 12 months ( n =39). We evaluated cross-sectional and longitudinal associations between infant residential and biomarker concentrations. A doubling of mean dust Pb concentration was consistently associated with 36–49% higher 12-month blood Pb adjusting for cord blood Pb ( P ⩽0.05). Adjusted dust concentration explained 29–35% of blood Pb variance, and consistent associations with other media were not observed. Although concentrations in dust and blood were generally low, strong and consistent associations between dust and body burden suggest that house dust in mining-impacted communities may impact children’s health. These relationships were observed at a young age, typically before blood Pb levels peak and when children’s development may be particularly vulnerable to toxic insult.

Children living near hazardous waste sites may be exposed to environmental contaminants, yet few studies have conducted multi-media exposure assessments, including residential environments where children spend most of their time. We sampled yard soil, house dust, and particulate matter with aerodynamic diameter <2.5 in 59 homes of young children near an abandoned mining area and analyzed samples for lead (Pb), zinc (Zn), cadmium (Cd), arsenic (As), and manganese (Mn). In over half of the homes, dust concentrations of Pb, Zn, Cd, and As were higher than those in soil. Proximity to mine waste (chat) piles and the presence of chat in the driveway significantly predicted dust metals levels. Homes with both chat sources had Pb, Zn, Cd, and As dust levels two to three times higher than homes with no known chat sources after controlling for other sources. In contrast, Mn concentrations in dust were consistently lower than in soil and were not associated with chat sources. Mn dust concentrations were predicted by soil concentrations and occupant density. These findings suggest that nearby outdoor sources of metal contaminants from mine waste may migrate indoors. Populations farther away from the mining site may also be exposed if secondary uses of chat are in close proximity to the home.