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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 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS. OBJECTIVE: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ~150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing. METHODS: Systematic review methods were used to identify and screen literature 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 inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement-only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams. DISCUSSION: Many of the ~150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large class of chemicals with widespread use and persistence in the environment and in humans; however, most of the epidemiology research has focused on a small subset. OBJECTIVES: The aim of this systematic evidence map (SEM) is to summarize the epidemiology evidence on approximately 150 lesser studied PFAS prioritized by the EPA for tiered toxicity testing, facilitating interpretation of those results as well as identification of priorities for risk assessment and data gaps for future research. METHODS: The Populations, Exposure, Comparators, and Outcomes (PECO) criteria were intentionally broad to identify studies of any health effects in humans with information on associations with exposure to the identified PFAS. Systematic review methods were used to search for literature that was screened using machine-learning software and manual review. Studies meeting the PECO criteria underwent quantitative data extraction and evaluation for risk of bias and sensitivity using the Integrated Risk Information System approach. RESULTS: 193 epidemiology studies were identified, which included information on 15 of the PFAS of interest. The most commonly studied health effect categories were metabolic (푛= 37), endocrine (푛= 30), cardiovascular (30), female reproductive (푛= 27), developmental (푛= 26), immune (푛= 22), nervous (푛= 21), male reproductive (푛= 14), cancer (푛= 12), and urinary (푛= 11) effects. In study evaluation, 120 (62%) studies were considered High/Medium confidence for at least one outcome. DISCUSSION: Most of the PFAS in this SEM have little to no epidemiology data available to inform evaluation of potential health effects. Although exposure to the 15 PFAS that had data was fairly low in most studies, these less-studied PFAS may be used as replacements for “legacy” PFAS, leading to potentially greater exposure. It is impractical to generate epidemiology evidence to fill the existing gaps for all potentially relevant PFAS. This SEM highlights some of the important research gaps that currently exist. [ABSTRACT FROM AUTHOR]

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 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS. OBJECTIVE : SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ~ 150 PFAS that were priori- tized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing. METHODS : Systematic review methods were used to identify and screen literature 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 inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with =21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata RESULTS: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams. DISCUSSION: Many of the ~ 150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343 [ABSTRACT FROM AUTHOR]