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Identification of Biotransformation Products (BPs) in Rats Exposed to 6:1 Fluorotelomer Alcohol (6:1 FTOH)
Citation:
Brennan, A., S. Shaut, A. Renyer, R. Payne, J. Ford, M. Devito, M. Hughes, L. Wehmas, AND D. Macmillan. Identification of Biotransformation Products (BPs) in Rats Exposed to 6:1 Fluorotelomer Alcohol (6:1 FTOH). SETAC, Louisville, KY, November 12 - 16, 2023. https://doi.org/10.23645/epacomptox.24526438
Impact/Purpose:
Poster presented to the Society of Environmental Toxicology and Chemistry (SETAC) North America 44th Annual Meeting November 2023
Description:
Fluorotelomer alcohols (FTOHs) are precursors and intermediates to the toxic, persistent, and bioaccumulative perfluorocarboxylic acids and are of concern to human health and the environment. To better understand the toxicity and risk from FTOHs, male and female rats were orally dosed with 6:1 FTOH for five days at dose-levels ranging from 0.1 to 300 mg/kg/day. Plasma was collected 24 hours after the last dose at study termination (or on day 6). Preliminary internal dose results in plasma suggest that rats quickly metabolize 6:1 FTOH. Therefore, the identification of biotransformation products is useful for understanding the adverse effects observed (decreased body weight and mortality at the highest dose levels). A SCIEX X500R liquid chromatography-quadrupole time-of-flight in negative electrospray ionization mode was used to detect and identify biotransformation products based on high-resolution accurate mass and fragmentation fingerprints collected using data-independent and data-dependent acquisition scans. Chemical transformation predictions were used to build suspect screening lists and guide identification. SCIEX Analytics Software was used to initially screen data based on comparison to vendor and in-house spectral libraries. SCIEX MarkerView Software was used to identify features that were unique and dose-dependent across treatment groups using statistical analyses. The use of t-tests and principal component analysis greatly reduced the features of interest. Preliminary results in plasma showed a tentative match of a predicted biotransformation product, perfluoroheptanoic acid (PFHpA), to an in-house spectral library with a library hit score of 100% and mass error of less than 1 ppm. The feature tentatively identified as PFHpA was also observed to be one of the most abundant peaks with significant differences (p < 0.001) observed across treatment groups. The Environmental Protection Agency’s Hazard Comparison Dashboard classifies PFHpA hazard scores as very high for genotoxic mutagenicity and high for both endocrine disruption and oral acute toxicity, suggesting potential mammalian health effects from 6:1 FTOH (and likely PFHpA) exposure. The abstract does not reflect EPA policies.
URLs/Downloads:
DOI: Identification of Biotransformation Products (BPs) in Rats Exposed to 6:1 Fluorotelomer Alcohol (6:1 FTOH)
PRESENTATION.PDF (PDF, NA pp, 992.423 KB, about PDF)