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Category-Based Toxicokinetic Evaluations of Data-Poor Per and Polyfluoroalkyl Substances (PFAS) by Gas Chromatography Coupled with Mass Spectrometry
Citation:
Wetmore, B., A. Kreutz, Matt Henderson, M. Phillips, L. Albrecht, L. McMillan, AND M. Clifton. Category-Based Toxicokinetic Evaluations of Data-Poor Per and Polyfluoroalkyl Substances (PFAS) by Gas Chromatography Coupled with Mass Spectrometry. Society of Toxicology, San Diego, CA, March 27 - 31, 2022. https://doi.org/10.23645/epacomptox.19371335
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Description:
Concern over exposure to and potential health effects of per- and polyfluoroalkyl substances (PFAS) has increased significantly as more is learned about their widespread environmental presence, persistence, and bioaccumulative potential. The limited measurement, monitoring, toxicokinetic (TK), and toxicologic data currently available is inadequate to inform risk evaluations across this diverse domain. In this study, approximately 75 gas chromatography (GC) amenable PFAS were selected for in vitro TK evaluation to expand our knowledge across several PFAS structural and functional groupings, including PFAS alcohols, fluorotelomer alcohols, amides, and acrylates. Targeted analytical methods were developed using gas chromatography coupled with mass spectrometry (GC/MS); ultracentrifugation was used to measure human plasma protein binding (PPB) and 20-donor pools of human hepatocyte suspensions were used in a substrate depletion approach to measure in vitro clearance (Clint). Method development was successful in plasma for >50 PFAS, with fraction unbound (fu) values ranging from 0.005-1, with 25th and 50th percentiles at 0.03 and 0.09, respectively. Compared to liquid chromatography (LC) amenable PFAS fu measures in a companion effort, these values show 10-fold lower binding overall. Trend analyses across a range of groupings were conducted; and include an increase in chain length associated with lower fu, and an inverse relationship between low van der Waals volume and high fu. Several but not all acrylates were unstable in plasma. Of the 49 PFAS with methods developed in hepatocyte media, over 30 were found to be highly unstable, with many exceeding 60% abiotic loss within 60 min after addition to media. Of those for which Clint was measured, values ranged from no clearance (hexafluoroamylene, pentafluoropropionamide) to 49.9 ¿l/min*million cells (1H,1H,10H,10H-Perfluorodecane-1,10-diol) with a median value of 17.31. Future efforts will use TK data in an in vitro-in vivo extrapolation approach to predict doses required to achieve systemic concentrations consistent with in vitro points of departure from high throughput screening efforts. The views expressed in this abstract are those of the authors and do not necessarily represent the views or policies of the US EPA.
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DOI: Category-Based Toxicokinetic Evaluations of Data-Poor Per and Polyfluoroalkyl Substances (PFAS) by Gas Chromatography Coupled with Mass Spectrometry
2022_SOT_WETMORE_PFAS-GC_TK_ANAL_V5.PDF (PDF, NA pp, 670.66 KB, about PDF)