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In-vivo and in-vitro quantitation and stability of fluorotelomer compounds in rat and human plasma to inform toxicity
Citation:
Brennan, A., L. Albrecht, M. Phillips, J. Ford, B. Wetmore, L. Wehmas, M. Hughes, AND M. Devito. In-vivo and in-vitro quantitation and stability of fluorotelomer compounds in rat and human plasma to inform toxicity. Society of Toxicology, San Diego, CA, March 27 - 31, 2022. https://doi.org/10.23645/epacomptox.19376039
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Description:
Due to their widespread use and persistence, per- and polyfluoroalkyl substances (PFAS) are of potential concern to human health and the environment. To better understand toxicity and risk, accurate determination of internal dose and biotransformation of PFAS in biological matrices at low concentrations from exposure assays is needed. A method was developed for targeted quantitation of two non-ionic PFAS, 6:1 fluorotelomer alcohol (6:1 FTOH) and 10:2 fluorotelomer acrylate (10:2 FTAcr) in plasma. Method detection limits (MDL) for both 6:1 FTOH and 10:2 FTAcr were approximately 1 ng/mL using a protein precipitation extraction with methanol and analysis on a gas chromatography tandem mass spectrometer. The validated method was used to quantitate PFAS concentrations in plasma collected during two 5-d in-vivo rat dose response studies. The nine dose levels for 6:1 FTOH and 10:2 FTAcr ranged from 0 to 96 and 0 to 1000 mg/kg/d, respectively; plasma was collected 24-h after the 5th dose (at study termination). Data from this study and the literature for other fluorotelomer compounds suggest that rats quickly metabolize these PFAS. For 6:1 FTOH, only the highest three and four dose levels for female and male rats, respectively, had plasma concentrations above the MDL. There was an observed decrease in terminal body weight and rate of body weight gain for rats from the highest dose levels for 6:1 FTOH. For 10:2 FTAcr, plasma samples from male and female rats had concentrations that were below the MDL. There was no observed decrease in terminal body weight and rate of body weight gain for rats from the highest dose levels for 10:2 FTAcr. A separate in-vitro study of 10:2 FTAcr in human plasma and hepatocyte cell media was conducted to evaluate compound stability. Human plasma and hepatocyte media were spiked at 10 and 1 µM, respectively, and kept at 37 °C for up to 360 minutes. After 60 minutes, there was a 74% and 86% loss in 10:2 FTAcr in human plasma and hepatocyte media, respectively. The instability of both fluorotelomers in plasma and rapid metabolism indicate that identifying the biotransformation products, especially of 6:1 FTOH, is necessary for understanding the observed adverse effects. The abstract does not necessarily reflect EPA policies.
URLs/Downloads:
DOI: In-vivo and in-vitro quantitation and stability of fluorotelomer compounds in rat and human plasma to inform toxicity
BRENNANAA SOT POSTER 2022 SAN DIEGO CA_20220309_FINAL.PDF (PDF, NA pp, 536.923 KB, about PDF)