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Internal Dose of Selected PFAS (Perfluoro-3-methoxypropanoic acid and) in Rat Plasma from Short Term Dosing Studies
Citation:
Renyer, A., D. MacMillan, M. Devito, M. Hughes, AND L. Wehmas. Internal Dose of Selected PFAS (Perfluoro-3-methoxypropanoic acid and) in Rat Plasma from Short Term Dosing Studies. 69th Annual American Society for Mass Spectrometry (ASMS) Conference, Philadelphia, Pennsylvania, October 31 - November 04, 2021. https://doi.org/10.23645/epacomptox.16814986
Impact/Purpose:
Poster for the 69th Annual American Society for Mass Spectrometry (ASMS) Conference on Oct. 31 - Nov. 4, 2021
Description:
Per- and polyfluoroalkyl substances (PFAS) are of growing concern due to their increasing environmental presence and persistence. Current estimates put the number of PFAS over 4700 yet only a select few have available toxicological data. To provide a rapid, less costly assessment of potential toxicity than possible with traditional 90-day and 2-year studies, a series of 5-day oral exposures to 8 dose levels of PFAS plus vehicle control were initiated. 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. Plasma concentrations for the first of these involving exposures to either perfluoro-3-methoxypropionic acid (PF-MOPA) or perfluoro-2,5,8-trimethyl-3,6,9-trioxadodecanoic acid (PF-TODoA) will be presented. Male and female Sprague-Dawley rats dosed via oral gavage to either PF-MOPA ranging from 0.4-677.3 mg/kg/day or PF-TODoA ranging from 0.3-335 mg/kg/day. Plasma samples were collected on day 6 and prepared using protein precipitation and isotope dilution in a 96-well plate format. Target analytes were determined using a Sciex x500R QTOF operated in multiple reaction monitoring mode with electrospray ionization and negative ion polarity. Due to the wide range of exposures, multiple dilution schemes with separate matrix-matched calibrations were employed to quantitate internal dose. Chromatographic separation was achieved with gradient elution paired with a Phenomenex Kinetex XB-C18 (100 × 2.1 mm) column. Methods were validated prior to analysis of study samples. Protein precipitation was selected for extraction of PFAS due to its simplicity, ruggedness, and applicability to analytes over a wide range of chemistries. Plasma was diluted by factors ranging from 400 to 6 with matrix-matched curves generated with each to accommodate the anticipated plasma levels. The method demonstrated good precision (RPD ≤ 24%) and accuracy (108 – 109% Recovery). Extraction efficiency increased and matrix effect decreased with higher levels of sample dilution. Limits of quantitation for both PF-MOPA and PF-TODoA were in the low ng/mL range. Matrix-matched calibrations were acceptable with r ≥ 0.995. Instrument source parameters and chromatography were optimized for each analyte. Potential contamination by PF-MOPA and PF-TODoA was routinely evaluated through analysis of solvent blanks and commercial rat plasma. PF-MOPA plasma concentrations from male rats were determined to range from 56.0 μg/mL for the 677.3 mg/kg/day dose to 1.38 ng/mL for the 0.4 mg/kg/day dose. 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 processing of the chemical between sexes. Further details of method validation and results for internal dose of PF-MOPA and PF-TODoA will be presented. Disclaimer: This abstract does not necessarily reflect EPA policy.
URLs/Downloads:
DOI: Internal Dose of Selected PFAS (Perfluoro-3-methoxypropanoic acid and) in Rat Plasma from Short Term Dosing Studies
ASMS PHILLY POSTER V7.PDF (PDF, NA pp, 449.256 KB, about PDF)