Toxicokinetics of 8:2 fluorotelomer alcohol (8:2-FTOH) in male and female Hsd:Sprague Dawley SD rats after intravenous and gavage administration

Abstract

Fluorotelomer alcohols (FTOHs) are used in the production of persistent per- and polyfluorinated alkyl substances (PFAS). Rodents and humans metabolize FTOHs to perfluoralkyl carboxylic acids which have several associated toxicities. Thus, understanding the toxicokinetics of these FTOHs and their metabolites will be useful for interpreting their toxicity for humans. Here, male and female Hsd:Sprague-Dawley SD rats were administered a single dose of 8:2-FTOH via gavage (males: 12, 24, 48 mg/kg; females: 40, 80, 160 mg/kg) or IV (males: 12 mg/kg; females: 40 mg/kg). Toxicokinetics of 8:2-FTOH and two primary metabolites, perfluorooctanoic acid (PFOA) and 7:3-fluorotelomer acid (7:3-FTA) were determined in plasma. Concentrations (total) of these chemicals were determined in the liver, kidney, and brain. There was rapid absorption and distribution of 8:2-FTOH after gavage administration in male rats. The plasma elimination half-life ranged from 1.1 to 1.7 hours. Kinetic parameters of 8:2-FTOH in females were similar to that in males. Bioavailability of 8:2-FTOH ranged from 22 to 41% for both sexes with no dose-dependent trends. 8:2-FTOH metabolites, PFOA and 7:3-FTA were detected in plasma following administration of the parent FTOH. Consistent with existing literature, the plasma half-life of PFOA was longer in males than in females (198–353 hours and 4.47–6.9 hours, respectively). The plasma half-life of 7:3-FTA was around 2–3 days in both sexes. 8:2-FTOH and 7:3-FTA were detected in all tissues; PFOA was found in the liver and kidney but not the brain. Detectable concentrations of metabolites persisted longer than the parent FTOH. These data demonstrate that in rats given a single gavage dose, 8:2-FTOH is rapidly absorbed, metabolized to form PFOA and 7:3-FTA, distributed to tissues, and eliminated faster than its metabolites. Sex differences were observed in the tissue distribution and elimination of PFOA, but not 8:2-FTOH and 7:3-FTA. Keywords: Perfluorinated chemicals, Fluorotelomer alcohols, Rats, Toxicokinetic