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Internal dose and in-life results after short-term exposure of rats to short-chain PFAS
Citation:
Bounds, J., A. Renyer, AND D. Macmillan. Internal dose and in-life results after short-term exposure of rats to short-chain PFAS. Presented at SERMACS, Durham, NC, October 25 - 28, 2023. https://doi.org/10.23645/epacomptox.24585240
Impact/Purpose:
Environmental distribution of PFAS and their potential for toxicity highlight the need to evaluate risks to human health. Short-term dosing studies may help reduce gaps in toxicological information for a wide variety of potentially harmful, data-poor chemicals. We determined plasma concentrations from rats dosed over a 5-day period with one of three emerging per- and polyfluoroalkyl substances (PFAS): perfluoro-3-methoxypropanoic acid (MOPA), perfluorohexanesulfonamide (PFHxSA), or 3:3 fluorotelomer carboxylic acid (3:3 FTCA). We observed widely different plasma concentrations for the three PFAS given at the same dose levels as well significant differences in results between male and female rats. The present effort provides evidence of in vivo persistence and potential bioaccumulation as well as varied biological response for emerging PFAS. These data will inform in vivo distribution and fate of PFAS and contribute to model development and risk assessment.
Description:
Per- and polyfluoroalkyl substances (PFAS) are a diverse array of more than 10,000 chemicals that are widely used in manufacturing and consumer products due to beneficial properties such as strong C-F bonds and resistance to water, oil, and grease. The environmental distribution of PFAS and potential for toxicity highlight the need to evaluate risks to human health. United States manufacturers halted production and use of perfluorooctanoic (PFOA) and perfluorooctane sulfonic acid (PFOS) after studies linked them to adverse health effects. Legacy PFAS have been replaced with emerging PFAS that often have different head groups and ether-linked carbon chains. Our work seeks to quickly fill toxicological data gaps for emerging PFAS through short-term oral exposure studies of male and female Sprague-Dawley rats. Rats were dosed daily for 5 days with one of three PFAS (perfluoro-3-methoxypropanoic acid (MOPA), perfluorohexanesulfonamide (PFHxSA), or 3:3 fluorotelomer carboxylic acid (3:3 FTCA)) or a vehicle control. Clinical signs of toxicity and body weight changes were minimal. Plasma was collected 24 hr after the final dose. Internal dose was determined after protein precipitation by liquid chromatography/ tandem mass spectrometry (LC/MS/MS) using negative ion multiple reaction monitoring mode with electrospray ionization. MOPA was dosed over a range of 0.01 to 300 mg/kg/day; PFHxSA and 3:3 FTCA dosages were 0.01 to 100 mg/kg/day. MOPA was not observed above the limit of quantitation (LOQ) of 16 ng/mL in plasma from rats dosed at 0.01, 0.1, 0.3, 1, 3, and 10 mg/kg/day. Plasma MOPA concentrations from rats dosed at 30, 100, and 300 mg/kg/day ranged from 20.8 - 994 ng/mL. Plasma concentrations at these dose levels for male rats were significantly higher (p < 0.05) than those for female rats. For PFHxSA dosed rats, preliminary plasma concentrations for the 0.01 mg/kg/day dose group were approximately 25 ng/mL. Preliminary data from all higher dose groups (0.1, 0.3, 1, 3, 10, 30, and 100 mg/kg/day) gave plasma PFHxSA concentrations above 500 ng/mL. For the 3:3 FTCA dosed rats, preliminary results for plasma concentrations were below the LOQ (34 ng/mL) for the 0.01 mg/kg/day, approximately 130 - 270 ng/mL for the 0.1 and 0.3 mg/kg/day dose groups, and above 500 ng/mL for the 1 mg/kg/day and higher dose groups. The differences in observed plasma concentrations suggest differences in biological response and toxicokinetics for these emerging PFAS in rats. Disclaimer: The views expressed in this abstract are those of the authors and do not necessarily reflect the statements, opinions, views, conclusions, or policies of the United States Environmental Protection Agency.
URLs/Downloads:
DOI: Internal dose and in-life results after short-term exposure of rats to short-chain PFAS
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