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Internal dose of perfluoro-3-methoxypropanoic acid in rat plasma and in-life effects from short term dosing studies
Citation:
Renyer, A., D. MacMillan, M. Devito, M. Hughes, AND L. Wehmas. Internal dose of perfluoro-3-methoxypropanoic acid in rat plasma and in-life effects from short term dosing studies. Society of Toxicology, San Diego, CA, March 27 - 31, 2022. https://doi.org/10.23645/epacomptox.19341683
Impact/Purpose:
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Description:
Concern over the exposure of per-and polyfluoroalkyl substances (PFAS) has risen because of their detection in the environment, persistence, and bioaccumulation. A series of 5-day oral exposures to eight dose levels of PFAS plus vehicle control were initiated to provide a rapid, less costly assessment of potential toxicity than possible with traditional 90-day and 2-year studies. Quantitation of internal dose, along with toxicogenomics, will yield primary points of departure based upon benchmark dose response modeling and enable timely risk prioritization for less-well studied PFAS. The objective of this study was to assess the internal dose and in-life effects in rats exposed to perfluoro-3-methoxypropionic acid (PF-MOPA). Male and female Sprague-Dawley rats (8-10 weeks) were dosed via oral gavage to PF-MOPA ranging from 0.4-677.3 mg/kg/day in water.. Plasma was collected on day 6. An analytical method was developed and validated for the quantification of target analytes using HPLC-high resolution accurate mass spectrometry. Plasma was diluted by factors ranging from 6 to 400 with matrix-matched curves (r ≥ 0.995) generated with each to accommodate the anticipated plasma levels. The method demonstrated good precision (RPD ≤ 11%) and accuracy (98-101%). Limits of quantitation for PF-MOPA were in the low ng/mL range. PF-MOPA plasma concentrations from male rats were determined to range from 1.32 ng/mL to 20.4 µg/mL for the 1.1. and 677.3 mg/kg/day dose, respectively. The PF-MOPA concentrations in plasma from female rats were found to be approximately 2-18 times less than those observed from males at corresponding dose levels above 3.2 mg/kg/day, suggesting differential disposition of the chemical between sexes. Males had a higher body weight gain across all concentrations than females. Males and females dosed at 677.3 mg/kg/day had a decrease in average body mass of at least 50 g and showed thin hair, rough coats (males), and piloerection (females). Preliminary data from this exposure suggests that the animals were exhibiting toxicity across all dose levels, with the severity increasing with dose range. Consideration of internal dose and in-life effects of PFAS are important to their overall toxicologic characterization. Disclaimer: This abstract does not necessarily reflect EPA policy.
URLs/Downloads:
DOI: Internal dose of perfluoro-3-methoxypropanoic acid in rat plasma and in-life effects from short term dosing studies
SOT SANDIEGO 2022 V7.1.PDF (PDF, NA pp, 363.255 KB, about PDF)