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
Dzierlenga A.L, Robinson V.G, Waidyanatha S, DeVito M.J, Eifrid M.A, Gibbs S.T, Granville C.A, *Blystone C.R
Poly- and perfluorinated alkyl substances (PFAS) are widely distributed, environmentally persistent chemicals associated with a broad range of health outcomes. The National Toxicology Program evaluated the subchronic toxicity of several PFAS in rats. Additionally, toxicokinetic (TK) studies were conducted to provide context for toxicologic findings, and to facilitate extrapolation to human exposures. Here, plasma TK parameters and tissue (i.e., liver, kidney, brain) concentrations are reported for perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), or perfluorodecanoic acid (PFDA) after a single-dose administration in male and female Hsd:Sprague Dawley ® (SD) rats. Generally, Tmax and elimination half-lives were longer, and clearance was slower with PFAS of longer chain length. Male rats administered PFOA had a prolonged half-life compared to females (215 hours compared to 2.75), with females displaying a faster clearance than males and a lower systemic exposure evidenced in plasma areas under the curve (AUC). Females treated with PFHxA also had a slightly shorter half-life (2 hours vs 9) than males and a faster clearance than males with a lower plasma AUC, although this difference was not as pronounced as PFOA. There was not a prominent sex difference following PFDA administration in half-lives (66 days in males, 52 in females). Female rats administered PFDA had higher plasma AUC/dose than males, and a slower clearance. PFDA had the highest measured liver tissue levels of the PFAS studied, whereas renal levels were highest in PFHxA- and PFOA-treated females. Profiling the toxicokinetics of straight chain legacy PFAS allows for comparison of the different classes, and a more direct translation of rodent toxicity to human populations.