Toxicokinetics of perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in male and female Hsd:Sprague dawley SD rats following intravenous or gavage administration

Abstract

1. Poly- and perfluorinated alkyl substances (PFAS) are environmentally persistent chemicals associated with many adverse health outcomes. The National Toxicology Program evaluated the toxicokinetics (TK) of several PFAS to provide context for toxicologic findings.

2. Plasma TK parameters and tissue (liver, kidney, brain) concentrations are reported for perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) or perfluorodecanoic acid (PFDA) after single-dose administration in male and female Hsd:Sprague-Dawley^® (SD) rats.

3. Generally, longer T_max and elimination half-lives, and slower clearance f, were correlated with longer chain length. Male rats administered PFOA had a prolonged half-life compared to females (215 h vs. 2.75), while females had faster clearance and smaller plasma area under the curve (AUC). Females administered PFHxA had a shorter half-life (2 h vs. 9) than males and faster clearance with a smaller plasma AUC, although this was less pronounced than PFOA. There was no sex difference in PFDA half-life. Female rats administered PFDA had a higher plasma AUC/dose than males, and a slower clearance. PFDA had the highest levels in the liver of the PFAS evaluated.

4. Profiling the toxicokinetics of these PFAS allows for comparison among subclasses, and more direct translation of rodent toxicity to human populations.

Keywords:

• Perfluorinated chemicals
• toxicokinetics
• PFHxA
• PFOA
• PFDA

Acknowledgements

The authors extend their gratitude to Steve Ferguson and Esra Mutlu for their critical review of the manuscript.

Disclosure statement

The authors have no conflict of interest to disclose.

Additional information

Funding

This work was performed for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract HHSN273201000016C.