A Chemical Category-Based Prioritization Approach for Selecting 75 Per- and Polyfluoroalkyl Substances (PFAS) for Tiered Toxicity and Toxicokinetic Testing

Abstract

Summary: Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated substances of interest to researchers, regulators, and the public due to their widespread presence in the environment. A few PFASs have comparatively extensive amounts of human epidemiological, exposure, and experimental animal toxicity data (e.g., perfluorooctanoic acid), whereas little toxicity and exposure information exists for much of the broader set of PFASs. Given that traditional approaches to generate toxicity information are resource intensive, new approach methods, including in vitro high-throughput toxicity (HTT) testing, are being employed to inform PFAS hazard characterization and further ( in vivo ) testing. The U.S. Environmental Protection Agency (EPA) and the National Toxicology Program (NTP) are collaborating to develop a risk-based approach for conducting PFAS toxicity testing to facilitate PFAS human health assessments. This article describes the construction of a PFAS screening library and the process by which a targeted subset of 75 PFASs were selected. Multiple factors were considered, including interest to the U.S. EPA, compounds within targeted categories, structural diversity, exposure considerations, procurability and testability, and availability of existing toxicity data. Generating targeted HTT data for PFASs represents a new frontier for informing priority setting. https://doi.org/10.1289/EHP4555

Fisheries Volume 45 Number 3 March 2020

“…Since it is not designated or regulated as a hazardous or toxic material, AFFF continues to be held widely. Newly developed safer foams are proprietary and the shorter-chain PFAS (e.g., GenX) used in them are not comprehensively tested for toxicity (Hubal 2019 ;Patlewicz et al 2019 ). There are thousands of PFAS compounds that remain untested for harmful effects (Patlewicz et al 2019 ), resulting in a daunting situation for regulators concerned with product manufacturing, human health, and environmental integrity.…”

Per‐ and Polyfluoroalkyl Substances (PFAS): Anglers May Be Exposed to Harmful Chemicals in Their Catch

“…Newly developed safer foams are proprietary and the shorter‐chain PFAS (e.g., GenX) used in them are not comprehensively tested for toxicity (Hubal ; Patlewicz et al. ). There are thousands of PFAS compounds that remain untested for harmful effects (Patlewicz et al.…”

“…There are thousands of PFAS compounds that remain untested for harmful effects (Patlewicz et al. ), resulting in a daunting situation for regulators concerned with product manufacturing, human health, and environmental integrity.…”

“…Evidence exists that PFAS compounds such as PFOS and PFOA may pose significant health risks to humans (Patlewicz et al. ). Currently, unmitigated PFAS environmental contamination is occurring across the USA (and in certain locales internationally).…”

“…In the United States, there is an urgent need for consistent and enforceable regulations regarding PFAS contamination and manufacture to prevent further spread of contamination and danger to public health. Evidence exists that PFAS compounds such as PFOS and PFOA may pose significant health risks to humans (Patlewicz et al 2019). Currently, unmitigated PFAS environmental contamination is occurring across the USA (and in certain locales internationally).…”