Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)
Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 EPA Per- and Polyfluoroalkyl Substances (PFAS) Action Plan (U.S. EPA, 2019a) outlines a multi-program national research plan to address the challenge of PFAS (U.S. EPA, 2019a). One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS. Objectives: To use Systematic Evidence Map (SEM) methods to summarize the available epidemiological and animal bioassay evidence for a set of ~150 PFAS that were prioritized in 2019 by the EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing. Methods: Systematic review methods were used to search for literature that was screened using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could be informative for human hazard identification. In addition, a variety of supplemental content was tracked, including studies presenting information on in vitro model systems; non-mammalian model systems; exposure-measurement -only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies that met the PECO criteria after full-text review were briefly summarized with respect to study design and health system(s) were assessed. Because animal bioassay studies with a ≥ 21 day exposure duration (or reproductive/developmental study design) were most useful to the planned CCTE analyses, these studies underwent study evaluation and a detailed data extraction. All data extraction is publicly available on-line as interactive visual formats with downloadable metadata. Results: Over 40,000 studies were identified from scientific databases. Screening processes identified 39 animal and 93 epidemiology studies from the peer reviewed literature and an additional 93 studies from grey literature sources that were considered to meet PECO criteria after full-text review. Human epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 35 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Conclusions: Many of the ~150 PFAS were data poor. By disseminating this information, we hope to facilitate additional assessment work and help identify key research needs.