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

Abstract

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.

Figure 1.

Workflow for selection of structural categories to identify the subset of 75 per- and polyfluoroalkyl substances (PFAS).

Figure 2.

Per- and polyfluoroalkyl substances (PFAS) Library characteristics by category aligned with workflow steps shown in Figure 1: (a) Total chemical count plot showing the total number of PFASs in a specific structural category color-coded by “status,” that is, membership on a single list (EPA PFAS WG $31>\text{EPA-PFAS}>\text{PFAS-Landscape}$); (b) ToxVal record count plot showing the number of PFASs with in vivo toxicity studies available within the category, as sourced from the U.S. EPA ToxVal database; (c) Same count plot as in a, showing only the final selected 75 PFAS substances by list membership and category representation. Color figures are available at https://doi.org/10.23645/epacomptox.7479866.