Application of Systematic Evidence Map Methods to Characterize Available Evidence for 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 outlines a multi-program national research plan to address the challenge of PFAS (U.S. EPA, 2019). One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS, especially those which are not the subject of existing or underway assessments by the US EPA. Objectives: To use Systematic Evidence Map (SEM) methods to summarize the available human 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 the literature that was screened included the using use of 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 characterization. In addition, a variety of supplemental content was tracked, including studies presenting information on in vitro model systems,; non-mammalian model systems,; exposure-level - 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 of a > 28 21 day duration of exposure duration (or reproductive/developmental study design) were most useful to the planned CCTE analyses, these studies underwent study evaluation and a full extraction of study methods detailed data extraction. All data extraction is publicly available on-line as in interactive visual formats with do that and can be downloaded .

Results

Over 40,000 studies were identified from scientific databases . Both machine-learning and manual screening processes were used to identified 39 animal and 93 epidemiology studies from the peer reviewed literature and an additional 93 studies from gray literature sources that were considered to meet PECO criteria-relevant after full-text review. Human epidemiological evidence was (available for 11 PFAS), which mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence was (available for 35 PFAS). The most commonly effects outcomes assessed in animals were observed in the 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 conducted by others and help identify key research needs.

Impact/Purpose

Evidence maps are an analysis that uses systematic review methods to compile and summarize available evidence, but do not reach any assessment hazard conclusions (or a toxicity value). They are considered a standalone publishable unit and represent the compilation of evidence that occurs during problem formulation and scoping. In this example, I hope you’ll see that SEMs can also be a useful tool for prioritization, identifying data gaps, or updating an existing assessment. The IRIS program began generating SEMs in 2019, and they are now becoming a routine analysis product within IRIS and PPRTV programs, as well as other fit for purpose assessment products. As you’ll see with this project, we’ve become adept with these workflows which is how we’ve allowed so much progress on a large chemical library in a relatively short time. As you’ll see with this project, we’ve become adept with these workflows which is how we’ve allowed so much progress on a large chemical library in a relatively short time.

Citation

Carlson, L. AND K. Thayer. Application of Systematic Evidence Map Methods to Characterize Available Evidence for Pfas. American Water Works Association Virtual PFAS Summit, Virtual, Virtual, February 10, 2021.