Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern.

Perfluoroalkyl acids (PFAAs), a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic (PBT) contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis. In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate. Low-dose effects include persistent delays in mammary gland development (perfluorooctanoic acid; PFOA) and suppression of immune response (perfluorooctane sulfonate; PFOS). In humans, even general population level exposures to some PFAAs are associated with health effects such as increased serum lipids and liver enzymes, decreased vaccine response, and decreased birth weight. Ongoing exposures to even relatively low drinking water concentrations of long-chain PFAAs substantially increase human body burdens, which remain elevated for many years after exposure ends. Notably, infants are a sensitive subpopulation for PFAA's developmental effects and receive higher exposures than adults from the same drinking water source. This information, as well as emerging data from future studies, should be considered in the development of health-protective and scientifically sound guidelines for PFAAs in drinking water.

The derivation of a Reference Dose (RfD) for perfluorooctane sulfonate (PFOS) based on immune suppression.

Exposure to perfluorooctane sulfonate (PFOS) is ubiquitous in populations and environments worldwide. Its long half-life in humans, indefinite persistence in the environment, and awareness of its widespread presence in drinking water make the human health assessment of PFOS a priority. While developmental, endocrine, and hepatic effects, and increased serum cholesterol are among the outcomes resulting from PFOS exposure, immunosuppression has also consistently emerged as an adverse effect. An in-depth review of the relevant scientific literature on the toxicology of PFOS has identified immunosuppression as a sensitive endpoint for PFOS toxicity. Here, we focus specifically on that endpoint and provide a detailed derivation of a Reference Dose (RfD) of 1.8 × 10-6 mg/kg/day for chronic human exposure to PFOS. This RfD is based on decreased plaque-forming cell (PFC) response in mice, an endpoint that reflects suppression of the immune response to a foreign antigen. We additionally identify two endpoints in the epidemiology literature, decreased vaccine response and increased incidence of childhood infections, that are associated with PFOS exposure and that are consistent with and support the decreased PFC response endpoint from animal studies. We provide a weight of evidence analysis integrating the evidence from animal and epidemiology endpoints. Finally, we compare this RfD to the PFOS RfD derived by the United States Environmental Protection Agency (USEPA) Office of Water based on a developmental endpoint. Based on this comparison, and given our assessment, the USEPA RfD does not provide sufficient protection against the adverse health effects of PFOS. The RfD derived herein is intended to be public health protective and appropriately minimizes PFOS exposure based on available evidence.

Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007-2010.

BACKGROUND: Perfluorinated chemicals (PFCs) are a group of manmade compounds that are not broken down in the body. Four PFCs (PFHxS, PFOS, PFOA, and PFNA) have been found in the blood of more than 98% of the United States population. OBJECTIVES: Our goal was to assess associations between PFHxS, PFOS, PFOA, and PFNA and uric acid, alanine transferase (ALT), gamma-glutamyl transferase (GGT), asparate aminotransferase (AST), alkaline phosphate (ALP), and total bilirubin in 2007-2008 and 2009-2010 combined National Health and Nutrition Examination Survey (NHANES). METHODS: We used multivariate linear regression and logistic regression adjusted for age, gender, race/ethnicity and BMI group, poverty, smoking, and/or alcohol consumption to estimate associations. Trend analysis was performed. RESULTS: PFHxS was associated with ALT. Each quartile of PFOS was statistically associated with total bilirubin [(Q2: OR=1.44, 95% CI 1.12-1.84), (Q3: OR=1.65, 95% CI 1.25-2.18), and (Q4: OR=1.51, 95% CI 1.06-2.15)], with evidence of an increasing trend (p-value=0.028). PFOA was associated with uric acid, ALT, GGT, and total bilirubin. PFNA was linearly associated with ALT (p-value <0.001), and there was statistically significant increasing trend (p-value=0.042). CONCLUSIONS: Our analysis found evidence of associations of biomarkers of liver function and uric acid with PFHxS, PFOS, PFOA, and PFNA at levels found in the general U.S. population.

Occurrence of perfluorinated compounds in raw water from New Jersey public drinking water systems.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were previously detected (≥ 4 ng/L) in 65% and 30%, respectively, of 23 New Jersey (NJ) public drinking water systems (PWS) sampled in 2006. We now report on a 2009 study of the occurrence of PFOA, PFOS, and eight other perfluorinated compounds (PFCs) in raw water samples from 30 intakes (18 groundwater and 12 surface water) from 29 additional NJ PWS. Between 1 and 8 PFCs were detected (≥ 5 ng/L) in 21 (70%) of 30 PWS samples at total PFC concentrations of 5-174 ng/L. Although PFOA was the most commonly detected PFC (57% of samples) and was found at the highest maximum concentration (100 ng/L), some of the higher levels of other PFCs were at sites with little or no PFOA. Perfluorononanoic acid was detected more frequently (30%) and at higher concentrations (up to 96 ng/L) than in raw or finished drinking water elsewhere, and it was found at several sites as the sole or predominant PFC, a pattern not reported in other drinking water studies. PFOS, perfluoropentanoic acid, and perfluorohexanoic acid were each detected in more than 20% of samples, while perfluoroheptanoic acid, perfluorobutane sulfonic acid, and perfluorohexane sulfonic acid were detected less frequently. Perfluorobutanoic acid was found only once (6 ng/L), and perfluorodecanoic acid was not detected. Total PFCs were highest in two reservoirs near an airfield; these were also the only sites with total perfluorosulfonic acids higher than total perfluorocarboxylic acids (PFCAs). PFC levels in raw and finished water from the same source were similar at those sites where both were tested. Five wells of two additional NJ PWS known to be contaminated with PFOA were also each sampled 4-9 times in 2010-13 for nine of the same PFCs. Total PFCs (almost completely PFCAs) at one of these PWS located near an industrial source of PFCs were higher than in any other PWS tested (up to 330 ng/L). These results show that multiple PFCs are commonly found in raw water from NJ PWS. Future work is needed to develop approaches for assessing the potential human health risks of exposure to mixtures of PFCs found in drinking water and other environmental media.

Future challenges to protecting public health from drinking-water contaminants.

Over the past several decades, human health protection for chemical contaminants in drinking water has been accomplished by development of chemical-specific standards. This approach alone is not feasible to address current issues of the occurrence of multiple contaminants in drinking water, some of which have little health effects information, and water scarcity. In this article, we describe the current chemical-specific paradigm for regulating chemicals in drinking water and discuss some potential additional approaches currently being explored to focus more on sustaining quality water for specific purposes. Also discussed are strategies being explored by the federal government to screen more efficiently the toxicity of large numbers of chemicals to prioritize further intensive testing. Water reuse and water treatment are described as sustainable measures for managing water resources for potable uses as well as other uses such as irrigation.

Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature.

Perfluorooctanoic acid (PFOA) is an anthropogenic contaminant that differs in several ways from most other well-studied organic chemicals found in drinking water. PFOA is extremely resistant to environmental degradation processes and thus persists indefinitely. Unlike most other persistent and bioaccumulative organic pollutants, PFOA is water-soluble, does not bind well to soil or sediments, and bioaccumulates in serum rather than in fat. It has been detected in finished drinking water and drinking water sources impacted by releases from industrial facilities and waste water treatment plants, as well as in waters with no known point sources. However, the overall occurrence and population exposure from drinking water is not known. PFOA persists in humans with a half-life of several years and is found in the serum of almost all U.S. residents and in populations worldwide. Exposure sources include food, food packaging, consumer products, house dust, and drinking water. Continued exposure to even relatively low concentrations in drinking water can substantially increase total human exposure, with a serum:drinking water ratio of about 100:1. For example, ongoing exposures to drinking water concentrations of 10 ng/L, 40 ng/L, 100 ng/L, or 400 ng/L are expected to increase mean serum levels by about 25%, 100%, 250%, and 1000%, respectively, from the general population background serum level of about 4 ng/mL. Infants are potentially a sensitive subpopulation for PFOA's developmental effects, and their exposure through breast milk from mothers who use contaminated drinking water and/or from formula prepared with contaminated drinking water is higher than in adults exposed to the same drinking water concentration. Numerous health endpoints are associated with human PFOA exposure in the general population, communities with contaminated drinking water, and workers. As is the case for most such epidemiology studies, causality for these effects is not proven. Unlike most other well-studied drinking water contaminants, the human dose-response curve for several effects appears to be steepest at the lower exposure levels, including the general population range, with no apparent threshold for some endpoints. There is concordance in animals and humans for some effects, while humans and animals appear to react differently for other effects such as lipid metabolism. PFOA was classified as "likely to be carcinogenic in humans" by the USEPA Science Advisory Board. In animal studies, developmental effects have been identified as more sensitive endpoints for toxicity than carcinogenicity or the long-established hepatic effects. Notably, exposure to an environmentally relevant drinking water concentration caused adverse effects on mammary gland development in mice. This paper reviews current information relevant to the assessment of PFOA as an emerging drinking water contaminant. This information suggests that continued human exposure to even relatively low concentrations of PFOA in drinking water results in elevated body burdens that may increase the risk of health effects.

Recent US State and Federal Drinking Water Guidelines for Per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFAS), a class of synthetic chemicals produced for over 70 years, are of increasing concern because of their widespread environmental presence, extreme persistence, bioaccumulative nature, and evidence for health effects from environmentally relevant exposures. In 2016, the United States Environmental Protection Agency (USEPA) established nonregulatory drinking water Health Advisories of 70 ng/L for individual and total concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the 8-carbon perfluoroalkyl acids (PFAAs) that are the most thoroughly studied PFAS. As of May 2020, 9 US states had concluded that the USEPA Health Advisories are insufficiently protective and developed more stringent PFOA and PFOS guidelines. In addition, 10 states had developed guidelines for other PFAS, primarily PFAAs. This Critical Review discusses the scientific basis for state and USEPA drinking water guidelines for PFOA and PFOS; the same principles apply to guidelines for other PFAS. Similarities and differences among guidelines arise from both toxicity and exposure considerations. The approximately 4-fold range among state guidelines (8-35 ng/L for PFOA, 10-40 ng/L for PFOS) is not large or unexpected for guidelines developed by different scientists at different time points, especially when compared with older USEPA and state guidelines that were generally several orders of magnitude higher. Additional state guidelines for PFOA, PFOS, and other PFAS are expected to become available. Environ Toxicol Chem 2021;40:560-563. © 2020 SETAC.

Investigation of levels of perfluoroalkyl substances in surface water, sediment and fish tissue in New Jersey, USA.

Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative, and toxic substances found in New Jersey (NJ) due to historic and current industrial activities and the use of aqueous film forming foams. This research documents PFAS occurrence in surface water, sediments, and fish tissue at 11 targeted waterbodies in NJ suspected to be impacted by PFAS. Thirteen PFAS compounds were quantified from each media. The profile of detected PFAS differed among media from the same site, with shorter chain PFAS tending to predominate in surface water while longer chain PFAS predominated in fish and sediments. All water samples contained detectable levels of at least four perfluoroalkyl substances. PFOA, PFHpA and PFPeA were detected at every site. ΣPFAS concentrations in water samples ranged from 22.9 to 279.5 ng/L. At least one, and up to eight, PFAS were detected in sediment samples at 10 sites, while there were no detections of PFAS in sediments at the reference site. ΣPFAS concentrations in sediment samples ranged from below detection to 30.9 ng/g. At least one fish of each species at every site had detectable levels of PFAS compounds. ΣPFAS concentrations in fish were highest at sites downstream from a military facility, and lowest at the reference site. PFOS, PFDA, PFUnA and PFDoA were the predominant PFAS detected in fish tissue. PFOS was generally found in fish tissue at higher concentrations than other PFAS, with higher PFOS concentrations found in the tissue of yellow perch, American eel, pumpkinseed, and largemouth bass collected at sites with higher detections of PFOS in surface waters. PFOS levels in nearly all fish species were, on average, high enough to trigger fish consumption advisories. Additional studies are needed to further evaluate the sources and occurrence of PFAS in NJ and to better understand their movement through the environment and potential risks.

Occurrence and potential significance of perfluorooctanoic acid (PFOA) detected in New Jersey public drinking water systems.

After detection of perfluorooctanoic acid (PFOA) in two New Jersey (NJ) public water systems (PWS) at concentrations up to 0.19 microg/L, a study of PFOA in 23 other NJ PWS was conducted in 2006. PFOA was detected in 15 (65%) of the systems at concentrations ranging from 0.005 to 0.039 microg/L. To assess the significance of these data, the contribution of drinking water to human exposure to PFOA was evaluated, and a health-based drinking water concentration protective for lifetime exposure of 0.04 microg/L was developed through a risk assessment approach. Both the exposure assessment and the health-based drinking water concentrations are based on the previously reported 100:1 ratio between the concentration of PFOA in serum and drinking water in a community with highly contaminated drinking water. The applicability of this ratio to lower drinking water concentrations was confirmed using data on serum levels and water concentrations from other communities. The health-based concentration is based on toxicological end points identified by U.S. Environmental Protection Agency (USEPA) in its 2005 draft risk assessment Recent information on PFOA's toxicity not considered in the USEPA risk assessment urther supports the health-based concentration of 0.04 microg/L. In additional sampling of 18 PWS in 2007-2008, PFOA in most systems was below the health-based concentration. However, PFOA was detected above the health-based concentration in five systems, including one not previously sampled.

Comments on article "Toxicity and carcinogenicity of chromium compounds in humans" by Costa and Klein.

The recent article by Costa and Klein (2006) contains several inaccuracies about the federal drinking water standard for chromium. The federal drinking water standard for chromium is 100 ppb, not 50 ppb as stated by Costa and Klein, and it is based on non-carcinogenic effects, not a one in one million cancer risk level. The question of whether or not hexavalent chromium is carcinogenic via the oral route is the focus of much current interest and has major implications for regulation of chromium in drinking water and soil. The chronic drinking water study of hexavalent chromium currently being conducted by the National Toxicology Program will provide further information that will be useful in addressing this question.