Optimizing Chemicals Management in the United States and Canada through the Essential-Use Approach.

Chemicals have improved the functionality and convenience of industrial and consumer products, but sometimes at the expense of human or ecological health. Existing regulatory systems have proven to be inadequate for assessing and managing the tens of thousands of chemicals in commerce. A different approach is urgently needed to minimize ongoing production, use, and exposures to hazardous chemicals. The premise of the essential-use approach is that chemicals of concern should be used only in cases in which their function in specific products is necessary for health, safety, or the functioning of society and when feasible alternatives are unavailable. To optimize the essential-use approach for broader implementation in the United States and Canada, we recommend that governments and businesses (1) identify chemicals of concern for essentiality assessments based on a broad range of hazard traits, going beyond toxicity; (2) expedite decision-making by avoiding unnecessary assessments and strategically asking up to three questions to determine whether the use of the chemical in the product is essential; (3) apply the essential-use approach as early as possible in the process of developing and assessing chemicals; and (4) engage diverse experts in identifying chemical uses and functions, assessing alternatives, and making essentiality determinations and share such information broadly. If optimized and expanded into regulatory systems in the United States and Canada, other policymaking bodies, and businesses, the essential-use approach can improve chemicals management and shift the market toward safer chemistries that benefit human and ecological health.

Evidence of Air Dispersion: HFPO-DA and PFOA in Ohio and West Virginia Surface Water and Soil near a Fluoropolymer Production Facility.

Perfluorooctanoic acid (PFOA) was used as a fluoropolymer manufacturing aid at a fluoropolymer production facility in Parkersburg, WV from 1951 to 2013. The manufacturer introduced a replacement surfactant hexafluoropropylene oxide dimer acid (HFPO-DA) that has been in use at this site since 2013. Historical releases of PFOA and related epidemiological work in this area has been primarily focused on communities downstream. To provide an update on the ongoing impacts from this plant, 94 surface water samples and 13 soil samples were collected mainly upstream and downwind of this facility. PFOA was detected in every surface water sample with concentrations exceeding 1000 ng/L at 13 sample sites within an 8 km radius of the plant. HFPO-DA was also found to be widespread with the highest levels (>100 ng/L) found in surface water up to 6.4 km north of the plant. One sample site, 28 km north of the plant, had PFOA at 143 ng/L and HFPO-DA at 42 ng/L. Sites adjacent to landfills containing fluorochemical waste had PFOA concentrations ranging up to >1000 ng/L. These data indicate that downwind atmospheric transport of both compounds has occurred and that the boundaries of the impact zone have yet to be fully delineated.

Are Fluoropolymers Really of Low Concern for Human and Environmental Health and Separate from Other PFAS?

Fluoropolymers are a group of polymers within the class of per- and polyfluoroalkyl substances (PFAS). The objective of this analysis is to evaluate the evidence regarding the environmental and human health impacts of fluoropolymers throughout their life cycle(s). Production of some fluoropolymers is intimately linked to the use and emissions of legacy and novel PFAS as polymer processing aids. There are serious concerns regarding the toxicity and adverse effects of fluorinated processing aids on humans and the environment. A variety of other PFAS, including monomers and oligomers, are emitted during the production, processing, use, and end-of-life treatment of fluoropolymers. There are further concerns regarding the safe disposal of fluoropolymers and their associated products and articles at the end of their life cycle. While recycling and reuse of fluoropolymers is performed on some industrial waste, there are only limited options for their recycling from consumer articles. The evidence reviewed in this analysis does not find a scientific rationale for concluding that fluoropolymers are of low concern for environmental and human health. Given fluoropolymers' extreme persistence; emissions associated with their production, use, and disposal; and a high likelihood for human exposure to PFAS, their production and uses should be curtailed except in cases of essential uses.

Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.

Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans.

U.S. domestic cats as sentinels for perfluoroalkyl substances: Possible linkages with housing, obesity, and disease.

Perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are persistent, globally distributed, anthropogenic compounds. The primary source(s) for human exposure are not well understood although within home exposure is likely important since many consumer products have been treated with different PFAS, and people spend much of their lives indoors. Herein, domestic cats were used as sentinels to investigate potential exposure and health linkages. PFAS in serum samples of 72 pet and feral cats, including 11 healthy and 61 with one or more primary disease diagnoses, were quantitated using high-resolution time-of-flight mass spectroscopy. All but one sample had detectable PFAS, with PFOS and perfluorohexane sulfonate (PFHxS) ranging from

Spatial and temporal patterns in concentrations of perfluorinated compounds in bald eagle nestlings in the upper Midwestern United States.

Perfluorinated chemicals (PFCs) are of concern due to their widespread use, persistence in the environment, tendency to accumulate in animal tissues, and growing evidence of toxicity. Between 2006 and 2011 we collected blood plasma from 261 bald eagle nestlings in six study areas from the upper Midwestern United States. Samples were assessed for levels of 16 different PFCs. We used regression analysis in a Bayesian framework to evaluate spatial and temporal trends for these analytes. We found levels as high as 7370 ng/mL for the sum of all 16 PFCs (∑PFCs). Perfluorooctanesulfonate (PFOS) and perfluorodecanesulfonate (PFDS) were the most abundant analytes, making up 67% and 23% of the PFC burden, respectively. Levels of ∑PFC, PFOS, and PFDS were highest in more urban and industrial areas, moderate on Lake Superior, and low on the remote upper St. Croix River watershed. We found evidence of declines in ∑PFCs and seven analytes, including PFOS, PFDS, and perfluorooctanoic acid (PFOA); no trend in two analytes; and increases in two analytes. We argue that PFDS, a long-chained PFC with potential for high bioaccumulation and toxicity, should be considered for future animal and human studies.

Determination of perfluorinated alkyl acid concentrations in biological standard reference materials.

Standard reference materials (SRMs) are homogeneous, well-characterized materials used to validate measurements and improve the quality of analytical data. The National Institute of Standards and Technology (NIST) has a wide range of SRMs that have mass fraction values assigned for legacy pollutants. These SRMs can also serve as test materials for method development, method validation, and measurement for contaminants of emerging concern. Because inter-laboratory comparison studies have revealed substantial variability of measurements of perfluoroalkyl acids (PFAAs), future analytical measurements will benefit from determination of consensus values for PFAAs in SRMs to provide a means to demonstrate method-specific performance. To that end, NIST, in collaboration with other groups, has been measuring concentrations of PFAAs in a variety of SRMs. Here we report levels of PFAAs and perfluorooctane sulfonamide (PFOSA) determined in four biological SRMs: fish tissue (SRM 1946 Lake Superior Fish Tissue, SRM 1947 Lake Michigan Fish Tissue), bovine liver (SRM 1577c), and mussel tissue (SRM 2974a). We also report concentrations for three in-house quality-control materials: beluga whale liver, pygmy sperm whale liver, and white-sided dolphin liver. Measurements in SRMs show an array of PFAAs, with perfluorooctane sulfonate (PFOS) being the most frequently detected. Reference and information values are reported for PFAAs measured in these biological SRMs.

Understanding the dynamics of physiological changes, protein expression, and PFAS in wildlife.

Per- and polyfluoroalkyl substances (PFAS) accumulation and elimination in both wildlife and humans is largely attributed to PFAS interactions with proteins, including but not limited to organic anion transporters (OATs), fatty acid binding proteins (FABPs), and serum proteins such as albumin. In wildlife, changes in the biotic and abiotic environment (e.g. salinity, temperature, reproductive stage, and health status) often lead to dynamic and responsive physiological changes that alter the prevalence and location of many proteins, including PFAS-related proteins. Therefore, we hypothesize that if key PFAS-related proteins are impacted as a result of environmentally induced as well as biologically programmed physiological changes (e.g. reproduction), then PFAS that associate with those proteins will also be impacted. Changes in tissue distribution across tissues of PFAS due to these dynamics may have implications for wildlife studies where these chemicals are measured in biological matrices (e.g., serum, feathers, eggs). For example, failure to account for factors contributing to PFAS variability in a tissue may result in exposure misclassification as measured concentrations may not reflect average exposure levels. The goal of this review is to share general information with the PFAS research community on what biotic and abiotic changes might be important to consider when designing and interpreting a biomonitoring or an ecotoxicity based wildlife study. This review will also draw on parallels from the epidemiological discipline to improve study design in wildlife research. Overall, understanding these connections between biotic and abiotic environments, dynamic protein levels, PFAS levels measured in wildlife, and epidemiology serves to strengthen study design and study interpretation and thus strengthen conclusions derived from wildlife studies for years to come.

Per- and polyfluoroalkyl substances in the environment.

Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water.

Polyfluorinated compounds: past, present, and future.

Interest and concern about polyfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and an increasing number of other related compounds is growing as more is learned about these ubiquitous anthropogenic substances. Many of these compounds can be toxic, and they are regularly found in the blood of animals and humans worldwide. A great deal of research has been conducted in this area, but a surprising amount remains unknown about their distribution in the environment and how people ultimately become exposed. The utility of these compounds seems to ensure their continued use in one form or another for the foreseeable future, presenting a long-term challenge to scientists, industry leaders, and public health officials worldwide.

Application of WWTP biosolids and resulting perfluorinated compound contamination of surface and well water in Decatur, Alabama, USA.

Perfluorinated chemicals (PFCs) such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been produced and used in a wide range of industrial and consumer products for many decades. Their resistance to degradation has led to their widespread distribution in the environment, but little is known about how humans become exposed. Recent studies have demonstrated that the application of PFC contaminated biosolids can have important effects on local environments, ultimately leading to demonstrable human exposures. This manuscript describes a situation in Decatur, Alabama where PFC contaminated biosolids from a local municipal wastewater treatment facility that had received waste from local fluorochemical facilities were used as a soil amendment in local agricultural fields for as many as twelve years. Ten target PFCs were measured in surface and groundwater samples. Results show that surface and well water in the vicinity of these fields had elevated PFC concentrations, with 22% of the samples exceeding the U.S. Environmental Protection Agency's Provisional Health Advisory level for PFOA in drinking water of 400 ng/L. Water/soil concentration ratios as high as 0.34 for perfluorohexanoic acid, 0.17 for perfluoroheptanoic acid, and 0.04 for PFOA verify decreasing mobility from soils with increasing chain length while indicating that relatively high transport from soils to surface and well water is possible.

Waste type, incineration, and aeration are associated with per- and polyfluoroalkyl levels in landfill leachates.

Per- and polyfluoroalkyl substances (PFAS) are found in many consumer products which will be ultimately disposed in landfills. Limiting environmental contamination and future exposures will require managing leachates from different types of landfills, each with different PFAS levels depending upon the source of the waste. The objective of this study was to evaluate the influence of waste type and on-site treatment on PFAS levels in landfill leachates. Eleven PFAS species (7 carboxylic acids, 3 sulfonic acids, and 5:3 fluorotelomer carboxylic acid) were evaluated in leachates from municipal solid waste (MSW), construction and demolition (C&D), MSW ash (MSWA), and a mixture of MSWA and MSW with landfill gas condensate (MSWA/MSW-GC). Leachates were also analyzed before and after on-site treatment at two of these facilities. Results indicate that MSWA leachate had significantly lower PFAS levels relative to other leachate types. Lower total PFAS concentrations in MSWA leachates were correlated with an increase in incineration temperature (R2 = 0.92, p = 0.008). The levels of PFAS in untreated C&D and untreated MSW leachate were similar. The levels of targeted PFAS species in MSW leachate for one of the facilities evaluated increased after on-site landfill treatment presumably due to the conversion of PFAS precursors in the untreated leachate sample.

Toxicity of Balb-c mice exposed to recently identified 1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2).

1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2) was first detected in 2012 in the Cape Fear River downstream of an industrial manufacturing facility. It was later detected in the finished drinking water of municipalities using the Cape Fear River for their water supply. No toxicology data exist for this contaminant despite known human exposure. To address this data gap, mice were dosed with PFESA-BP2 at 0, 0.04, 0.4, 3, and 6 mg/kg-day for 7 days by oral gavage. As an investigative study, the final dose groups evolved from an original dose of 3 mg/kg which produced liver enlargement and elevated liver enzymes. The dose range was extended to explore a no effect level. PFESA-BP2 was detected in the sera and liver of all treated mice. Treatment with PFESA-BP2 significantly increased the size of the liver for all mice at 3 and 6 mg/kg-day. At the 6 mg/kg-day dose, the liver more than doubled in size compared to the control group. Male mice treated with 3 and 6 mg/kg-day and females treated with 6 mg/kg-day demonstrated significantly elevated serum markers of liver injury including alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), and liver/body weight percent. The percent of PFESA-BP2 in serum relative to the amount administered was similar in male and female mice, ranged from 9 to 13 %, and was not related to dose. The percent accumulation in the liver of the mice varied by sex (higher in males), ranged from 30 to 65 %, and correlated positively with increasing dose level.

Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina.

BACKGROUND: From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents. Those PFAS included several fluoroethers including HFPO-DA also known as GenX. Little is known about the bioaccumulation potential of these fluoroethers. OBJECTIVE: We determined levels of fluoroethers and legacy PFAS in serum samples from Wilmington residents. METHODS: In November 2017 and May 2018, we enrolled 344 Wilmington residents ≥6 years of age into the GenX Exposure Study and collected blood samples. Repeated blood samples were collected from 44 participants 6 months after enrollment. We analyzed serum for 10 fluoroethers and 10 legacy PFAS using liquid chromatography-high-resolution mass spectrometry. RESULTS: Participants' ages ranged from 6 to 86 y, and they lived in the lower Cape Fear Region for 20 y on average (standard deviation: 16 y). Six fluoroethers were detected in serum; Nafion by-product 2, PFO4DA, and PFO5DoA were detected in >85% of participants. PFO3OA and NVHOS were infrequently detected. Hydro-EVE was present in a subset of samples, but we could not quantify it. GenX was not detected above our analytical method reporting limit (2 ng/mL). In participants with repeated samples, the median decrease in fluoroether levels ranged from 28% for PFO5DoA to 65% for PFO4DA in 6 months due to wastewater discharge control. Four legacy PFAS (PFHxS, PFOA, PFOS, PFNA) were detected in most (≥97%) participants; these levels were higher than U.S. national levels for the 2015-2016 National Health and Nutrition Examination Survey. The sum concentration of fluoroethers contributed 24% to participants' total serum PFAS (median: 25.3 ng/mL). CONCLUSION: Poorly understood fluoroethers released into the Cape Fear River by a fluorochemical manufacturing facility were detected in blood samples from Wilmington, North Carolina, residents. Health implications of exposure to these novel PFAS have not been well characterized. https://doi.org/10.1289/EHP6837.

Nontargeted mass-spectral detection of chloroperfluoropolyether carboxylates in New Jersey soils.

The toxicity and environmental persistence of anthropogenic per- and poly-fluoroalkyl substances (PFAS) are of global concern. To address legacy PFAS concerns in the United States, industry developed numerous replacement PFAS that commonly are treated as confidential information. To investigate the distribution of PFAS in New Jersey, soils collected from across the state were subjected to nontargeted mass-spectral analyses. Ten chloroperfluoropolyether carboxylates were tentatively identified, with at least three congeners in all samples. Nine congeners are ≥(CF2)7 Distinct chemical formulas and structures, as well as geographic distribution, suggest airborne transport from an industrial source. Lighter congeners dispersed more widely than heavier congeners, with the most widely dispersed detected in an in-stock New Hampshire sample. Additional data were used to develop a legacy-PFAS fingerprint for historical PFAS sources in New Jersey.

Determination of ten perfluorinated compounds in bluegill sunfish (Lepomis macrochirus) fillets.

A rigorous solid phase extraction/liquid chromatography/tandem mass spectrometry method for the measurement of 10 perfluorinated compounds (PFCs) in fish fillets is described and applied to fillets of bluegill sunfish (Lepomis macrochirus) collected from selected areas of Minnesota and North Carolina. The 4 PFC analytes routinely detected in bluegill fillets were perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (C10), perfluoroundecanoic acid (C11), and perflurododecanoic acid (C12). Measures of method accuracy and precision for these compounds showed that calculated concentrations of PFCs in spiked samples differed by less than 20% from their theoretical values and that the %RSD for repeated measurements was less than 20%. Minnesota samples were collected from areas of the Mississippi River near historical PFC sources, from the St. Croix River as a background site, and from Lake Calhoun, which has no documented PFC sources. PFOS was the most prevalent PFC found in the Minnesota samples, with median concentrations of 47.0-102 ng/g at locations along the Mississippi River, 2.08 ng/g in the St. Croix River, and 275 ng/g in Lake Calhoun. North Carolina samples were collected from two rivers with no known historical PFC sources. PFOS was the predominant analyte in fish taken from the Haw and Deep Rivers, with median concentrations of 30.3 and 62.2 ng/g, respectively. Concentrations of C10, C11, and C12 in NC samples were among the highest reported in the literature, with respective median values of 9.08, 23.9, and 6.60 ng/g in fish from the Haw River and 2.90, 9.15, and 3.46 ng/g in fish from the Deep River. These results suggest that PFC contamination in freshwater fish may not be limited to areas with known historical PFC inputs.

Gas-Phase Detection of Fluorotelomer Alcohols and Other Oxygenated Per- and Polyfluoroalkyl Substances by Chemical Ionization Mass Spectrometry.

Per- and polyfluoroalkyl substances (PFAS) are incorporated into an ever-increasing number of modern products and inevitably enter the environment and ultimately human bodies. Herein, we show that chemical ionization mass spectrometry with iodide reagent ion chemistry is a useful technique for the detection of fluorotelomer alcohols (FTOHs) and other oxygenated PFAS, including per- and polyfluoro carboxylic acids such as hexafluoropropylene oxide dimer acid. This technique offers direct, high-time resolution measurement capability with parts per trillion by volume (nanograms per cubic meter) gas-phase detection limits. Measurements were taken by direct volatilization of samples without prior processing, allowing for fast measurements and reduced sample treatment compared to established PFAS methods. We demonstrate the utility of this technique by sampling volatile and semivolatile PFAS from fluoro additives and fluoro products to quantify levels of FTOHs and identify additional fluorinated compounds for which standards were unavailable.

Per- and polyfluoroalkyl substances in two different populations of northern cardinals.

The northern cardinal (Cardinalis cardinalis) is a good indicator species for environmental contaminants because it does not migrate and its range covers a diversity of habitats, including metropolitan Atlanta, GA and the geographically isolated Hawaiian Islands. In addition, the cardinal is often found near people's homes, making it likely to be exposed to the same outdoor elements, including soil, groundwater, and air, that surrounding humans experience. In this study, blood serum concentrations of 12 per- and polyfluoroalkyl substances (PFASs) were measured in 40 cardinals from Atlanta and 17 cardinals from the Big Island (Hawaii), HI. We observed significantly higher median concentrations of four PFASs and significantly higher detection frequencies of seven PFASs in the cardinals from Atlanta, relative to the PFAS median concentrations and detection frequencies observed in the cardinals from Hawaii (α = 0.05). Among the PFASs measured, perfluorooctane sulfonate (PFOS) was observed in the highest concentrations. A linear regression model controlling for sex, age, and airport distance did not explain PFOS variation within the Atlanta samples, but a similar model explained 90% of PFOS variation within the Hawaii samples. To our knowledge, these are the first measurements of PFASs in northern cardinals.

Comparative hepatic effects of perfluorooctanoic acid and WY 14,643 in PPAR-alpha knockout and wild-type mice.

Perfluorooctanoic acid (PFOA) is a chemical used in the production of fluoropolymers. Its persistence in the environment and presence in humans and wildlife has raised health concerns. Liver tumor induction by PFOA is thought to be mediated in rodents by PPAR-alpha. A recent US EPA scientific advisory board questioned the contribution of PPAR-alpha in PFOA-induced liver tumors. Liver response in CD-1, SV/129 wild-type (WT), and PPAR-alpha knockout (KO) SV/129 mice was evaluated after seven daily treatments of PFOA-NH4(+) (1, 3, or 10 mg/kg, p.o.) or the prototype PPARalpha-agonist Wyeth 14,643 (WY, 50 mg/kg). Livers were examined by light and electron microscopy. Proliferation was quantified after PCNA immunostaining. PFOA treatment induced a dose-dependent increase in hepatocyte hypertrophy and labeling index (LI) similar to WY in WT mice. Ultrastructural alterations of peroxisome proliferation were similar between WY-treated and 10 mg/kg PFOA-treated WT mice. KO mice had a dose-dependent increase in hepatocyte vacuolation but increased LI only at 10 mg PFOA/kg. WY-treated KO mice were not different from KO control. These data suggest that PPAR-alpha is required for WY- and PFOA-induced cellular alterations in WT mouse liver. Hepatic enlargement observed in KO mice may be due to an accumulation of cytoplasmic vacuoles that contain PFOA.