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A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS)
Citation:
Judson, R., D. Smith, M. Devito, J. Wambaugh, B. Wetmore, K. Friedman, G. Patlewicz, R. Thomas, R. Sayre, J. Olker, S. Degitz, S. Padilla, J. Harrill, T. Shafer, AND K. Carstens. A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS). Society of Toxicology (SOT) 63rd Annual Meeting and ToxExpo, Salt Lake City, UT, March 10 - 14, 2024. https://doi.org/10.23645/epacomptox.25451677
Impact/Purpose:
Presentation to the Society of Toxicology (SOT) 63rd Annual Meeting and ToxExpo March 2024
Description:
Background and Purpose: Per- and polyfluoroalkyl substances (PFAS) are widely used in non-stick coatings, firefighting foams and other products. Their fluorinated state contributes to their unique uses and stability, but also may result in long half-lives in the environment and humans. There is increasing evidence that some of these compounds can be toxic, leading to immunosuppression, cancer, and other unwanted outcomes. Hundreds to thousands of PFAS are in commerce and the environment, but only a small fraction of these have been evaluated for toxicity using standard in vivo tests. This leads to a need to prioritize which of these compounds should be examined further. Here we demonstrate an approach to prioritizing PFAS by combining human biomonitoring data (blood concentrations) with bioactivity data (concentrations at which bioactivity is observed) from a battery of in vitro assays. The result is a risk metric, the margin of exposure (MoE) which is the bioactivity concentration divided by the blood concentration. Chemicals with low MoE values could then be prioritized for further risk assessment or risk management. Methods: We have combined in vitro points of departure from a separate study on ~150 PFAS with blood levels taken from a comprehensive literature survey and calculate MoE values. A total of 31 PFAS had all required data. Results: Two of these (PFOA and PFOS) have MoE values <1 for some populations. An additional 9 PFAS have MoE values <100 for some populations. Conclusions: We provide a discussion of multiple sources of uncertainty in the MoE calculation and conclude that this complete set of 11 PFAS with MoE<100 should be examined further. This study shows a promising approach to screening level risk assessments of compounds such as PFAS that are long-lived in human and other species and provides an approach for further studies being carried out at the US EPA. Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS)
PFAS BCBCR SOT 2024 POSTER FINAL_18MAR24.PDF (PDF, NA pp, 846.173 KB, about PDF)