Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Abstract

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 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 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 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 mo...

Epidemiology Evidence for Health Effects of 150 per- and Polyfluoroalkyl Substances: A Systematic Evidence Map

“…As part of a broader effort to characterize the evidence of health effects associated with exposure to less-studied PFAS, we created a systematic evidence map (SEM) of epidemiology studies of the approximately 150 less-studied PFAS prioritized by the U.S. Environmental Protection Agency (U.S. EPA) for tiered toxicity testing. 11 This SEM is an extension of another recently published SEM of these PFAS, 12 which presented detailed data on animal toxicology studies but only high-level summary study design characteristics (e.g., population, study design, and health effect categories) for epidemiology studies. This SEM uses the same literature search and screen results but adds to the previous analysis with full data extraction and study evaluation of the identified epidemiology studies, allowing the user to access the full quantitative results and risk of bias ratings when examining the available evidence.…”

“…High-level summary information as reported in Carlson et al. 12 is useful at the scoping stage to understand the quantity of available data but does not allow for users to assess the findings or utility of the available studies. The information in this SEM is being disseminated in downloadable formats and an interactive dashboard to facilitate further analyses.…”

Invited Perspective: The Promise of Fit-for-Purpose Systematic Evidence Maps for Supporting Regulatory Health Assessment

“…New methods that support improved efficiency and effectiveness of risk assessments, including the systematic evidence map described by Carlson et al. 1 in this issue, are greatly needed.…”

“…Carlson et al. 1 used machine learning tools to greatly improve the efficiency of the SEM workflow, including SWIFT-Active Screener, which iteratively prioritizes titles and abstracts for manual screening. The use of SWIFT-Active Screener for this purpose has been externally validated.…”

“…concluded that many of the they assessed were data poor. 1 Considering both SEMs, this comparison makes clear that there are many available studies on some that would not be used by the U.S. EPA in a regulatory context. However, it is our hope that such studies would be included in a meaningful way in the body of evidence that the U.S. EPA uses to inform health assessments.…”