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Dosimetry and Potential Bioaccumulation of a GenX Oligomer HFPO-TeA
Citation:
Renyer, A., B. Payne, M. Devito, M. Hughes, L. Wehmas, AND D. Macmillan. Dosimetry and Potential Bioaccumulation of a GenX Oligomer HFPO-TeA. Presented at SOT, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22272334
Impact/Purpose:
PFAS, currently numbering over 4700, have significant environmental presence and persistence yet only a select few have available toxicological data. The PFAS we are focusing on in this study is HFPO-TeA (perfluoro-(2,5,8-trimethyl-3,6,9-trioxadodecanoic) acid) that is related to GenX. GenX is a short-chain PFAS that was recently regulated in drinking water by the US EPA. To better understand toxicity, dosimetry, and bioaccumulation, male and female Sprague-Dawley rats were orally dosed with several levels of HFPO-TeA over 5 days. These results will aid in the development of short-term, 5-day exposures for more rapid assessment of potential hazards. The general public would be interested in these findings, as they will help guide a portion of the EPA's approach to PFAS going forward.
Description:
Acute and long-term exposure to per- and polyfluoroalkyl substances (PFAS) is of rising concern due to their persistent detection and abundance in the environment coupled with their potential for bioaccumulation. The replacement of legacy PFAS with ether-linked carboxylic acid (PFECA) fluorochemicals is creating new exposure concerns world-wide. For instance, the US EPA recently introduced a new health advisory level in drinking water for the PFECA GenX (2,2,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid) to decrease exposure. Perfluoro-(2,5,8-trimethyl-3,6,9-trioxadodecanoic) acid (HFPO-TeA) is an understudied oligomer of GenX that has been detected widely in China. However, little is known about its hazard, making it a priority with several States and EPA regions. To better understand toxicity, dosimetry, and bioaccumulation, male and female Sprague-Dawley rats were orally dosed with several levels of HFPO-TeA. Dose levels ranged from 0.3-335 mg/kg/day in corn oil. Liver tissue and blood were collected on day 6. HFPO-TeA internal dose levels were quantitated using liquid chromatography high resolution accurate mass spectrometry. PFAS were extracted from plasma and liver samples using a simple protein precipitation method with acidified acetontirile. Both sample types were paired with matrix-matched calibration curves (r ≥ 0.995) generated to accommodate the anticipated levels. The limit of quantitation in liver was 1.76 ng/mL tissue wet weight and in plasma was 8.9 ng/mL. No animals dosed above 17 mg/kg/day survived the length of the study. Male and female rats showed several clinical signs of toxicity at 17 and >6 mg/kg/day, respectively, including lethargy, abnormal breathing, and weight loss. Significant sex associated differences (p < 0.05) were observed in plasma dosimetry data at 6.3 and 17 mg/kg/day dose levels. HFPO-TeA plasma concentrations in female rats ranged from 0.565 ng/mL to 174 ng/mL for the 0.3 and 17 mg/kg/day doses, respectively. Plasma concentrations in male rats were approximately 1.3-2.5 times less than those observed in females at corresponding dose levels above 0.3 mg/kg/day. Internal dose HFPO-TeA levels increased linearly over the dose range for both males and females. Concentrations in plasma after 5 days were approximately 6 times higher than those collected after 2 hours of exposure. Concentrations of HFPO-TeA in liver did not show significant sex associated differences. Dosimetry and bioaccumulation data from this study will inform and expand our knowledge about the potential health hazard this GenX oligomer presents in this model system. Disclaimer: The views expressed in this abstract are those of the author(s) and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency.
URLs/Downloads:
DOI: Dosimetry and Potential Bioaccumulation of a GenX Oligomer HFPO-TeA
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