CDC/ATSDR’s Involvement in PFAS and Health
Patrick Breysse, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention

Per- and Polyfluoroalkyl Substances (PFAS) are man-made chemicals that have been used in industry and consumer products worldwide since the 1950s. These diverse group of chemicals are characterized by the strength of their carbon-fluorine bonds, which make them very stable and resistant to typical environmental degradation processes. During production and use, PFAS can migrate into the soil, water, and air. Most PFAS (including PFOA and PFOS) do not break down, so they remain in the environment. Because of their widespread use and their persistence in the environment, PFAS are found in the blood of people and animals all over the world and are present at low levels in a variety of food products and in the environment.

CDC/ATSDR are conducting activities to expand the scientific knowledge base regarding the relationship between exposure to PFAS and human health outcomes. CDC/ATSDR does this through exposure assessments, health studies and the development of Toxicological Profiles. CDC/ATSDR is in the process of creating a profile of exposure in 10 communities across the nation through exposure assessments, and recently announced the recipients of research cooperative agreements to complete the PFAS multi-site health study that will look at the relationship between PFAS exposure and health outcomes in communities affected by contaminated drinking water. CDC/ATSDR has been engaged in several key initiatives related to PFAS and also produced tools and resources for states and communities working to better understand and communicate about PFAS exposure.

As the PFAS-related knowledge base grows, CDC/ATSDR will leverage its unique capacity, resources, and partnerships across federal agencies, state and local partner organizations, and affected communities to ensure that programmatic priorities are dynamic and responsive to the evolving scientific landscape.

NC PFAS Testing Network: Overview of the Study
Jason Surratt, UNC Chapel Hill

The North Carolina Per- and Polyfluoroalkyl Substances Testing (PFAST) Network is a statewide research collaboration created in response to a legislative mandate and funding by the North Carolina General Assembly to help answer questions about exposure to PFAS chemicals throughout the state. The Network comprises Principal Investigators from NC State, Duke, UNC Chapel Hill, UNC Wilmington, UNC Charlotte, ECU and NC A&T who collectively received state funding through the NC Policy Collaboratory. PFAST Network scientists were charged with testing for current levels of PFAS chemicals in public drinking water sources (identified by the NC Department of Environmental Quality) across the entire state. In addition to this baseline water sampling and analysis, the Network was also asked to: (i) develop quantitative models to predict which private wells are most at risk of contamination from the discharge of PFAS, including GenX; (ii) test the performance of relevant technologies in removing such compounds; (iii) study the air emissions and atmospheric deposition of PFAS, including GenX; (iv) evaluate other research opportunities for improved water quality sampling and analyses techniques, data interpretation, and potential mitigation measures that may be necessary, with respect to the discharge of PFAS, including GenX; and (v) conduct additional research to increase knowledge regarding the potential adverse effects on human health, wildlife, and the environment.

NC PFAS Testing Network Results: Water Sampling and Analysis
Lee Ferguson, Duke University

PFASs have been found to contaminate drinking water sources in several locations throughout North Carolina. The sources of this contamination are in some cases well-understood, e.g fluorochemical manufacturing discharge to rivers, firefighting activities at military installations, and application of biosolids to agricultural fields leading to runoff into reservoirs. We have initiated a broad-ranging monitoring study to assess occurrence and map sources of PFAS compounds in drinking water sources across the state. Specifically, we have sampled 405 total drinking water sources and have analyzed these samples with a combination of targeted quantitative analysis measuring 47 distinct PFAS compounds, non-targeted analysis using ultra-high resolution tandem mass spectrometry, and adsorbable organic fluorine measurement. Results to-date indicate that PFAS enter NC drinking water sources from a variety of sources and that spatial variation in PFAS concentrations is high. We have measured sporadic groundwater and surface-water contamination with legacy PFAS including polyfluorinated carboxylic acids (PFCAs) and polyfluorinated sulfonic acids (PFSAs) at levels exceeding the 70 ng/L USEPA health advisory level as well as persistent elevated levels of new-generation PFAS such as GenX in waters downstream of a major fluorochemical manufacturing facility on the Cape Fear River. In addition, we have observed elevated levels of short-chain PFCAs in several surface-water sites on the Haw River, which were likely contributed by discharge of treated municipal wastewater upstream of the drinking water intakes. Some of these measured levels varied considerably between sample collection dates, highlighting the importance of frequent monitoring to capture transient PFAS inputs to receiving waters.

PFAS in North Carolina Air and Atmospheric Deposition
Barbara Turpin, UNC Chapel Hill

This presentation will report on the measurement of PFAS species in ambient air and wet/dry deposition in several locations across North Carolina. There are a limited number of measurements of PFAS in atmospheric gases, particles and precipitation, in urban and rural areas in many parts of the world. Possible atmospheric sources include primary emissions from industrial manufacturing, use of fire-fighting foams, use of consumer products, and volatilization of PFAS from contaminated soils/water and volatilization from urban waste streams (landfills and waste water treatment). However, there remains a paucity of knowledge regarding the atmospheric concentrations, gas-particle partitioning, reactions, and deposition of legacy and emergent PFAS, especially of the replacement compounds including shorter chain PFAS and perfluoroalkyl ether carboxylic acids.

Group A:  What are the missing links in our understanding of fate and transport of PFAS?

Bioaccumulation and Impacts of Novel and Legacy PFAS in Wildlife of Coastal North Carolina
Scott Belcher, NC State

PFAS are water-soluble chemicals of emerging concern that persist within the environment. These chemicals exhibit unique surfactant properties and are robustly stable, properties that make these compounds attractive components for a variety of industrial applications and consumer products. Surface water sampling reveals a significant prevalence of legacy PFAS, hexafluoropropylene oxide dimer acid (HFPO–DA; GenX) and other novel PFAS within the Cape Fear River; however, there is limited PFAS exposure data within the North Carolina aquatic ecosystem. There is also a critical lack of toxicokinetic data (absorption, distribution, elimination) necessary for hazard characterization, or to predict bioaccumulation potential of most legacy and emerging PFAS.

To understand the potential biological impacts in the wild and built environments, a number of critical questions must be answered, these include: “what physio/chemical properties of PFAS determinate bioaccumulation?”; “in what biological compartment do PFAS accumulate?”; and “what data is necessary to predict bioaccumulation or elimination properties of individual or classes of PFAS?”.

The objective of our ongoing studies is using untargeted high-resolution mass spectrometry to analyze bioaccumulation of novel and legacy PFAS, and to correlate PFAS concentrations with blood chemistry markers of health in American alligators (Alligator mississippiensis) and Striped bass (Morone saxatilis). In both alligators and striped bass sampled from the Cape Fear River, high levels of PFOS, other long-chain PFAS, and novel PFAS (Nafion byproduct 2 and GenX) were found to bioaccumulate in serum. PFOS and Nafion byproduct 2 were associated with biomarkers of altered immune (e.g. lysozyme) and liver function (e.g. aspartate aminotransferase). Continuing studies will examine PFAS in specific body compartments, including liver and muscle tissue of recreationally harvested species within the Cape Fear River (Flathead catfish, Largemouth bass, and American shad). Combined with those studies, a novel in vitro protein binding assay has been developed that can evaluate the binding properties of individual PFAS to serum albumin and other PFAS-binding proteins. Together these approaches will begin to eliminate some critical data gaps that currently limit the ability to relate PFAS chemical structures to their potential physiological impacts.

Discharge of PFAS from groundwater to surface water near the Fayetteville Works, North Carolina
Dave Genereux, NC State

Groundwater in the vicinity of the Fayetteville Works in Cumberland and Bladen Counties is heavily contaminated with PFAS. These contaminants are carried through the aquifer by the groundwater flow and discharge into surface water, including tributaries to the Cape Fear River. Important scientific and practical questions include “What is the rate of PFAS discharge from groundwater to surface water?” and “How long will it take for PFAS to flush out of the groundwater system?”

With regard to the first question, in 2018 and 2019, we estimated PFAS output from groundwater to Georgia Branch, a tributary to the Cape Fear River that joins the river just south of the Fayetteville Works. Using field methods developed to study chemical fluxes through streambeds and export from watersheds, we estimate that about 60 grams of PFAS discharge each day from groundwater into Georgia Branch, and flow from Georgia Branch into the Cape Fear River. About one-quarter of the PFAS export is “GenX” (i.e., HFPO-DA, or PFProPrA); almost all the rest is due to PMPA (the only PFAS found in higher concentration than GenX in these samples), PFO2HxA, PEPA, and PFMOAA.

The question about flushing time will be addressed with a combination of PFAS data and data on the age of groundwater as it arrives at Georgia Branch and other streams. Knowledge of possible PFAS sorption onto aquifer solids may also be relevant.

A Hydrogeological Modeling Approach to Understanding the Fate and Transport of PFAS in the Cape Fear Watershed
Jennifer Hoponick Redmon, RTI International

The fate and transport of PFAS in the Cape Fear Watershed of North Carolina is unique in geographical scale, varied sources, long exposure duration, and the distinct communities affected. The complex retentive nature of PFAS migration in soil to groundwater requires new modeling approaches beyond simple water-soil equilibrium partitioning. Additionally, the fate and transport of PFAS compounds at the air-water interface also require additional consideration. This presentation overviews an approach to model historical PFAS contamination of drinking water in three communities within the Cape Fear Watershed using available data and information. Limitations and uncertainties to understanding the complex nature of PFAS compounds will also be discussed. Key questions to consider include: 1) How can we use available data and information to most accurately reconstruct the historical fate and transport of PFAS compounds?; 2) What new data, information, or approaches do we need to improve modeling estimates?; 3) What role should laboratory studies, field studies, and modeling studies have in characterizing historical PFAS contamination?; and 4) What do we need to accurately estimate current and future PFAS fate and transport into drinking water?

Group B: Which alternative treatment and disposal options offer most promise?

Greensboro’s Response to PFAS in its Watershed and Drinking Water
Michael Borchers, City of Greensboro

With the City of Greensboro’s watershed investigation now complete, the Water Resources Department is leading the effort to proactively monitor and respond to the presence of PFAS in the city’s reservoirs and drinking water. From initial sample results collected under the Third Unregulated Contaminant Monitoring Rule (UCMR3) to partnering with Guilford County Department of Public Health and the State Division of Waste Management, the city has aggressively and proactively responded to the presence of these contaminants of emerging concern. Additional measures the city has taken to ensure the health and safety of its customers and uphold public trust include fostering relationships with key stakeholders, installing a temporary water treatment system, developing a fate and transport model, and authorizing a capital improvement plan to facilitate permanent treatment process improvements.

Removal of PFAS from drinking water by reverse osmosis membranes, residential filters, and a novel resin
Orlando Coronell, UNC Chapel Hill

As part of the work being performed by the PFAST Network, researchers are evaluating various existing technologies for their efficacy to remove PFAS from water. This talk will summarize results from ongoing studies on the efficacy of reverse osmosis/nanofiltration membranes, point-of-use residential filters, and a promising novel resin in development at UNC Chapel Hill to remove legacy and emerging PFAS from water.

Removal of PFAS from drinking water by activated carbon, ion exchange resin, and electrochemical oxidation
Mei Sun, UNC Charlotte

To address the PFAS contamination issue in North Carolina, researchers are evaluating treatment options to identify optimum technologies for removing both legacy and emerging PFASs from contaminated surface and ground waters in North Carolina as well as from finished drinking water. PFAS sequestration from drinking water sources by a wide range of commercially available activated carbons and ion exchange resins are characterized. In addition, PFAS degradation by electrochemical oxidation is evaluated as a potential disposal method for waste streams generated during resin regeneration and membrane filtration.

Group C: How can emerging knowledge about PFAS be factored into risk assessment?

Descriptive toxicological approaches to understand health risks of understudied PFAS
Jamie DeWitt, East Carolina

Replacement. Understudied. Emerging. Novel. These words have been used to describe the PFAS detected in the Cape Fear River of North Carolina and in other areas where PFAS detectives use a variety of approaches to uncover PFAS in water. Toxicologically, these words mean that little to no health-related data are publicly available, which can limit decision-making about public health protection. We have therefore focused our efforts on providing toxicological data for understudied per- and polyfluoroether acids (PFEAs). Descriptive toxicological endpoints were collected from male and female C57BL/6 mice orally exposed to one of four PFEAs for 30 days. Body weights throughout the dosing period, organ weights at necropsy, markers of liver enzyme activity, and immune organ cellularity were evaluated for three-, four-, five-, and seven-carbon PFEAs. Exposure to these selected PFEAs did not elicit dose-responsive decreases in body weight, lymphoid organ weights and cellularity, or increases in liver weights across administered doses or when compared to perfluorooctanoic acid (PFOA), a “legacy” PFAS with a known toxicological profile. However, some doses of these PFEAs did alter these endpoints at the highest administered doses and in comparison with PFOA. Some of these PFEAs also appear to be rapidly excreted in a mouse model, leading to low internal concentrations. These findings indicate that some PFAS may produce adverse health outcomes at certain administered doses, but that additional studies are warranted to understand how toxicokinetic factors influence toxicological outcomes.

Comparison of health effects following oral exposures to PFOA and GenX in pregnant mice
Sue Fenton, National Institute of Environmental Health Sciences

In an effort to evaluate the health effects of replacement PFAS, we have chosen the several sensitive endpoints affected by PFOA in mice as comparators. HFPO-DA or GenX, measured in river water in North Carolina and other states, was compared to PFOA in CD-1 mouse studies designed to evaluate effects on fetal growth, adult and pup liver morphology, weight gain, and mammary gland morphology. GenX mirrored PFOA in many ways – it significantly increased gestational weight gain, relative liver weight, liver pathologic findings, placental weight, % abnormal placentae, and significantly decreased triglyceride levels and mammary gland development. However, GenX also exhibited differences from PFOA – PFOA consistently decreased fetal weight at term and GenX effects were marginal, the type of abnormalities in the placenta differed by compound, GenX and PFOA had varied effects on placental thyroid hormone content, and GenX did not accumulate in the liver to the extent of PFOA, yet exhibited similar hepatic effects at the cellular level. Ongoing studies are evaluating transcriptomic pathways affected by these PFAS in sensitive target tissues in hopes of enhancing targeted testing of replacement PFAS in the future.

PFAS and Placental Toxicity
Rebecca Fry, UNC Chapel Hill

In ongoing research we are assessing the effects of PFAS on the placenta using both clinical samples as well as in vitro models of toxicity. A total of 22 PFAS were measured in 122 placentas from a high-risk pregnancy cohort at UNC. Of the 22 PFAS investigated, 11 PFAS were detected in at least one placenta, and of those 11, 4 were detected in 50% or more of samples. Similar placental levels of PFOS and PFOA levels were observed when compared to cohorts in China and Denmark. Risk-factors associated with elevated PFAS in the 122 placentas were assessed. PFHxS in the placenta were significantly higher in smoking mothers compared to non-smoking mothers, and maternal race/ethnicity was associated with significant differences in PFUnA levels. No significant associations were observed between in PFAS levels and gestational age in the current study. In addition to measuring PFAs in the placentas, we assessed the effect of PFAS on placental trophoblasts in an in vitro model. First, we determined internal cellular accumulation levels in serum and serum free media conditions at 10, 100, 1,000, and 10,000 ng/mL for PFOS, PFOA, and GenX. Then we measured trophoblast migration using an in vitro scratch assay and found that 1000 ng/mL PFOS, PFOA, and GenX each decreased the rate of trophoblast migration over 24 h. Treatment with PFOS, PFOA, and GenX also decreased trophoblast expression of chemokines (e.g. CCL2, CCL7), chemokine receptors (e.g. CCR4, CCR7), and inflammatory enzymes (e.g. ALOX15, NOS2) involved in migration. These data highlight the presence of PFAS in the placenta and the potential impact in the signaling of critical biological pathways.

THURSDAY, OCTOBER 24

Controlling PFAS at the Source: Legal Obligations and Liability
Geoff Gisler, Southern Environmental Law Center

PFAS are often described as unregulated. Is that true? Are there regulatory tools that the states and federal governments can use to control PFAS at the source? Does common law provide a solution? This presentation will review the purpose of the Clean Water Act, the tools it includes, and potential pitfalls for PFAS dischargers. It will include a summary of common law issues that are the subject of ongoing litigation related to The Chemours Company’s Fayetteville Works Facility in North Carolina.

Potential Solutions for PFAS: NIEHS Superfund Research Program Remediation Research
Heather Henry, National Institute of Environmental Health Sciences

Addressing the complex human health and environmental issues related to PFAS requires innovative, multidisciplinary approaches. The NIEHS Superfund Research Program (SRP) advances solutions to issues like PFAS through grant support to universities and small businesses with the central goal to understand and break the link between chemical exposure and disease. The SRP portfolio includes broad research areas advancing our understanding of PFAS exposures, hazards, and potential solutions, as well as communicating results to communities and stakeholders. This presentation will give a brief overview of treatment options for PFAS and will focus on SRP grantee efforts to develop new approaches to remediate PFAS in the environment and drinking water. These novel extraction, removal, and destruction technologies show promise in reducing the time and cost required to achieve cleanup goals. Also important are groundwater modeling tools to predict how PFAS move in the subsurface, helping to understand where to target remediation approaches. In addition, researchers are developing new tools to measure PFAS in the environment including passive sampling devices and Geographical Information Systems (GIS)-based databases for identifying areas of high PFAS exposure risk. Collectively, ongoing SRP grantee activities, will improve our understanding of the impact of these emerging contaminants, which will lead to lower environmental cleanup costs, reduced risk of exposure, and improvements in human health.

Industry Perspective on Understanding and Abating Organic Fluorinated Compounds
Sean Uhl and Amber Wellman, Chemours Fluoroproducts

Water quality and emerging contaminants are growing concerns across the United States, and rightly so. One focus of this concern is a class of fluorinated chemicals called PFAS. The term PFAS, however, represents a broad and diverse range of compounds that have a variety of physical and chemical properties, health and environmental profiles, uses, and benefits. It is important to understand the proper way to group PFAS into categories and classes based on their unique properties in order to provide focus and enable a science-based approach to analytical methodology, abatement technology, hazard assessment and regulation.

Chemours has worked diligently to create more sensitive analytical methods and synthesize authentic reference standards, when no commercial standards or analytical methods were available, and has made significant R&D investment in abatement technology. Chemours continues to focus on safe manufacture of products that are essential to modern life. This presentation will discuss the high-level classifications within the PFAS group of compounds and an overview of abatement technologies utilized and being studied at Chemours manufacturing sites to determine appropriate abatement approaches to specific classes of PFAS.