title: Inhalation and oral toxicokinetics of 6:2 FTOH and its metabolites in mammals.
abstract: The toxicokinetics of 6:2 fluorotelomer alcohol (6:2 FTOH) and its terminal perfluorinated and polyfluorinated metabolites (PFBA, PFHxA, PFHpA and 5:3 Acid) have been calculated from laboratory studies of rats and from a biomonitoring study of humans. In vitro studies with mouse, rat and human hepatocytes indicate qualitatively similar metabolic pathways of 6:2 FTOH. In a one-day inhalation study of 6:2 FTOH in rats, PFBA, PFHxA, PFHpA and 5:3 Acid were determined to be the major metabolites in plasma with calculated elimination half-lives of 1.3-15.4h and metabolic yields up to 2.7 mol%. In five-day and 23-day inhalation studies and a 90-day oral study of 6:2 FTOH, the plasma or serum concentration profile of 5:3 Acid was several-fold higher than concentrations observed in the single day study, resulting in an estimated elimination half-life of 20-30 d. In contrast, the concentrations of PFBA, PFHxA and PFHpA showed little or no concentration increase with repeated exposure. Elimination half-lives of PFHxA, PFHpA and 5:3 Acid in humans were estimated from a study of professional ski wax technicians who were occupationally exposed to aerosolized and volatilized components of fluorinated glide wax. The resulting human elimination half-life values of PFHxA, PFHpA and 5:3 Acid were 32, 70 and 43 d, respectively. Based on a one compartment toxicokinetic model, current environmental air concentrations of 6:2 FTOH are estimated to result in plasma concentrations of PFHxA, PFHpA and 5:3 Acid that are less than or equal to typical LOQ values, in agreement with extant biomonitoring results.
authors.affiliation: DuPont Haskell Centers for Health and Environmental Sciences, E. I. duPont de Nemours and Company, Inc., 1090 Elkton Road, Newark, DE 19711-3507, USA. Electronic address: Mark.H.Russell@dupont.com.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Russell
authors.affiliation: DuPont Haskell Centers for Health and Environmental Sciences, E. I. duPont de Nemours and Company, Inc., 1090 Elkton Road, Newark, DE 19711-3507, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Himmelstein
authors.affiliation: E. I. duPont de Nemours and Company, Inc., Chemicals and Fluoroproducts, 974 Centre Road, Wilmington, DE 19805, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Buck
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D006207:Half-Life; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D066007:Toxicokinetics
chemical_list: D005466:Fluorocarbons
keywords: Fluorotelomer; Human; Inhalation; Kinetics; Oral; Rat