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Nontargeted analysis for identification of PFAS biotransformation products in rat plasma.
Citation:
MacMillan, D., A. Renyer, M. Devito, M. Hughes, AND L. Wehmas. Nontargeted analysis for identification of PFAS biotransformation products in rat plasma. SETAC NTA, Durham, NC, May 22 - 26, 2022. https://doi.org/10.23645/epacomptox.19758634
Impact/Purpose:
Biotransformation product data improve our understanding of in vivo disposition of PFAS and contribute to an important aspect of their risk assessment.
Description:
Per- and polyfluorinated substances (PFAS) are frequently used in industrial processes and commercial products, leading to environmental contamination, exposure, and the potential for adverse health effects. With toxicological data available for only a few of the more than 4700 known PFAS, the US Environmental Protection Agency is using short term exposure studies to establish interim benchmark dose levels for emergent PFAS and to promote understanding of the biological responses to PFAS exposure. Introduced exogenous chemicals are often biochemically transformed in biological systems to increase water solubility and promote elimination. Little is known about biotransformations of PFAS, however. Here we present results of nontargeted analysis (NTA) of plasma to identify potential biotransformation products from rats exposed over five days to multiple concentrations of perfluoro(2,5,8-trimethyl-3,6,9-trioxadodecanoic) acid (PF-TODoA) or 2,2,3,3-tetrafluoro-3-(trifluoromethoxy) propionic acid (PF-MOPA). Extracts were analyzed on a Sciex X500R QTOF using independent data analysis (IDA) and sequential window acquisition of all theoretical mass spectra (SWATH) scanning. Data were processed with Sciex OS 2.1 and MarkerView 1.3.1. BioTransformer 3.0 was used to predict PFAS metabolites. Several biotransformations were predicted for PF-TODoA, a twelve carbon perfluoroether carboxylic acid. At least two ions with masses consistent with predicted biotransformations were observed from PF-TODoA-exposed rat plasma. For both ions, formulas with less than 5 ppm mass error compared to the predicted products were generated with Sciex OS. One ion was tentatively identified as the molecular ion of the product formed by O-dealkylation of the PF-TODoA carboxylate moiety to give an alcohol. The MS/MS spectrum included ions that are similarly observed for PF-TODoA. All acquired spectra were searched also for the presence of fragments consistent with structural components of a PF-TODoA precursor. Numerous instances of characteristic fragments were detected, suggesting the presence of additional species of interest. The only biotransformation predicted for PF-MOPA, a small four carbon carboxylic acid, was O-glucuronidation, which was not observed in initial experiments. Results of additional analysis to gain insights into the identities of unknowns will be presented. Disclaimer: This abstract does not necessarily reflect EPA policy.
URLs/Downloads:
DOI: Nontargeted analysis for identification of PFAS biotransformation products in rat plasma.
MACMILLAN SETAC NTA MAY 2022.PDF (PDF, NA pp, 656.434 KB, about PDF)