Science Inventory

Application of a Quality Scoring System for Assessing Per- and Polyfluoroalkyl Substances (PFAS) in Organic Solvents for In Vitro Toxicokinetic Testing

Citation:

Smeltz, M., M. Clifton, Larry - RTP McMillan, M. Devito, AND B. Wetmore. Application of a Quality Scoring System for Assessing Per- and Polyfluoroalkyl Substances (PFAS) in Organic Solvents for In Vitro Toxicokinetic Testing. SETAC North America 42nd Annual Meeting, Virtual, Virtual, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.16879327

Impact/Purpose:

This poster will be presented at the 42nd Annual SETAC meeting being held virtually in November 2021 and is focused on the development of a quality scoring system to assess PFAS stock solutions. More than 450 unique PFAS-organic solvent stocks were assessed by mass spectrometry to guide further in vitro testing by providing a pass/fail score with informational flags. One application of this scoring system was to assess plasma protein binding, a toxicokinetic property that informs bioaccumulative potential, on more than 60 PFAS, where most chemicals displayed very high binding rates.

Description:

PFAS represent a large chemical class for which limited toxicity and toxicokinetic information is available. Given the persistent and bioaccumulative properties for legacy PFAS, category or grouping strategies are being employed using in vitro new approach methodologies (NAMs) to evaluate the larger PFAS space. One critical aspect to ensuring accurate and complete evaluation of PFAS is the quality of the material being assessed. Numerous organic solvents, including dimethyl sulfoxide (DMSO) and ethanol, are used as diluents for in vitro evaluation. Using mass spectrometry approaches, a quality scoring system was created to provide a simple pass or fail notation with descriptive flags for each PFAS stock by examining for parent mass and impurities. 201 unique PFAS prepared in 469 stock solutions were assessed through this scoring system, where 75 unique PFAS were investigated by liquid chromatography mass spectrometry (LC-MS) and 126 were characterized by gas chromatography mass spectrometry (GC-MS). Most failed LC-MS examined PFAS belonged to the hexafluoropropylene oxide acid family in DMSO, including GenX, while 60 GC-MS amenable PFAS with predicted low boiling points were discarded due to failure to detect during analysis. Failed stocks have been removed from use in any EPA in vitro evaluations. Ultimately, over 115 PFAS in DMSO stocks received passing quality scores to allow for further in vitro testing. In vitro measures of PFAS plasma protein binding (PPB), a toxicokinetic property used to inform PFAS bioaccumulative potential, were generated across the LC-MS PFAS DMSO stocks. PPB measures by ultracentrifugation showed very high binding rates [i.e., fraction unbound (Fu) = 0.001for perfluorooctanoic acid] across 75% of PFAS examined. Six PFAS with high predicted water solubility exhibited less protein binding, with Fu values ≥0.10, including hexafluoroglutaric acid (Fu = 0.53). For perfluoroalkyl carboxylic acids, increasing chain length exhibited higher PPB (C3: perfluoropropanoic acid Fu = 0.31; C10: perfluorodecanoic acid Fu = 0.003). This stock quality scoring system provides an informed guide on how to proceed with performing in vitro experiments to advise NAM-anchored, risk-based assessment of PFAS. The views expressed in this abstract are those of the authors and do not necessarily represent the views or policies of the US EPA.