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Evaluations of in vivo and in vitro dosimetry and metabolic biotransformation of the hexafluoropropylene oxide homologue HFPO-TeA, an emerging per-and polyfluoroalkyl substance (PFAS)
Citation:
MacMillan, D., A. Renyer, M. Smeltz, M. Phillips, K. Ravindra, M. Devito, M. Hughes, L. Wehmas, AND B. Wetmore. Evaluations of in vivo and in vitro dosimetry and metabolic biotransformation of the hexafluoropropylene oxide homologue HFPO-TeA, an emerging per-and polyfluoroalkyl substance (PFAS). SETAC, Pittsburgh, PA, November 13 - 17, 2022. https://doi.org/10.23645/epacomptox.21552594
Impact/Purpose:
These data are improving our understanding of HFPO homologue biotransformation and disposition, enabling a more robust risk-based evaluation of a key emerging PFAS group.
Description:
High levels and persistence of legacy per- and polyfluoroalkyl substances (PFAS) in the environment and organisms along with potential adverse effects led to government restrictions, voluntary phase outs, and the need for replacements with similarly useful but less toxic properties. Emerging PFAS such as hexafluoropropylene oxide (HFPO) homologues are used in fluoropolymer manufacture as alternatives to perfluorooctanoic acid. Recent detection of perfluoro-2,5,8-trimethyl-3,6,9-trioxadodecanoic acid (HFPO-TeA) in surface waters combined with the dearth of hazard data creates potential for exposure with unknown health effects. The US Environmental Protection Agency conducted a 5-day dose-response study in male and female Sprague-Dawley rats to evaluate in vivo hazard, dosimetry, and HFPO-TeA biotransformation products (BTPs). After daily administration of HFPO-TeA at doses ranging from 0.3 to 335.2 mg/kg/day, in-life observations showed signs of toxicity including weight loss and abnormal breathing. Female rats lost weight starting at the 6.3 mg/kg/day dose; weight loss for males did not occur until the 17 mg/kg/day dose. Plasma, liver, and kidney were collected to evaluate internal dose and target tissue disposition, and probe for BTPs. Targeted analysis of plasma collected 24 hr after the 5th dose revealed significantly higher HFPO-TeA in female rats than males at doses of 2.3 mg/kg/day and above. Non-targeted analysis (NTA) revealed potential BTPs of HFPO-TeA, including perfluoro-2,5-trimethyl-3,6-dioxanonanoic acid (HFPO-TA), which was present in plasma of both sexes, but at a lower abundance in females. Data visualization showed separation of the data from exposed plasma and controls, and clustering according to sex. Cross-species and cross-sex evaluations of in vitro hepatocyte clearance and plasma protein binding are underway to further characterize sex and species differences and conduct in vitro-in vivo comparisons of HFPO-TeA internal dosimetry estimation and biotransformation characterization. Determinations of HFPO-TeA and BTP levels in liver and kidney are also underway to round out evaluations of target tissue dosimetry and metabolic biotransformation. These data are improving our understanding of HFPO homologue biotransformation and disposition, enabling a more robust risk-based evaluation of a key emerging PFAS group. Disclaimer: This abstract does not necessarily represent the views or policies of the US Environmental Protection Agency.
URLs/Downloads:
DOI: Evaluations of in vivo and in vitro dosimetry and metabolic biotransformation of the hexafluoropropylene oxide homologue HFPO-TeA, an emerging per-and polyfluoroalkyl substance (PFAS)
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