title: Toxicokinetics of perfluorooctanoate (PFOA) in rainbow trout (Oncorhynchus mykiss).
abstract: Rainbow trout (Oncorhynchus mykiss) confined to respirometer-metabolism chambers were dosed with perfluorooctanoate (PFOA) by intra-arterial (i.a.) injection and sampled to obtain concentration time-course data for plasma, urine, and expired water. The data were then analyzed by compartmental modeling to estimate rates of renal and branchial clearance. Averaged across all animals, the renal clearance rate (1.35mL/h/kg) was more than ten times greater than the branchial clearance rate (0.12mL/h/kg). The average whole-body elimination half-life was 12.6d, which is somewhat longer than values obtained in previous studies with smaller trout. The tissue distribution of PFOA was assessed by collecting tissues at the end of chambered exposures and in a separate tissue time-course experiment. From the time-course study it appeared that an internal steady-state was established within 24h of i.a. injection. Consistent with previous studies, the rank order of PFOA concentration in tissues at steady state was: plasma>liver>kidney>muscle. In a second set of chambered experiments, fish were exposed to PFOA in water to determine the rate of branchial uptake. Branchial uptake rates were too low to assess directly by measuring PFOA concentrations in inspired and expired water. Uptake rate constants (mean 0.19L/d/kg; 0.1% uptake efficiency) were therefore estimated by compartmental modeling using plasma concentration time-course data and model parameters derived from the elimination experiments. It is clear from this effort that elimination of PFOA by trout occurs primarily via the renal route. This finding is consistent with numerous studies of mammals and suggests that trout possess membrane transporters that facilitate the movement of PFOA from plasma to urine.
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Consoer
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Hoffman
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Fitzsimmons
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kosian
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA. Electronic address: nichols.john@epa.gov.
authors.forename: John W
authors.initials: JW
authors.lastname: Nichols
mesh_terms: D000818:Animals; D002210:Caprylates / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D006207:Half-Life; D008657:Metabolic Clearance Rate; D017686:Oncorhynchus mykiss / Q000502:physiology*; D014018:Tissue Distribution; D066007:Toxicokinetics; D014874:Water Pollutants, Chemical / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; D014874:Water Pollutants, Chemical; C023036:perfluorooctanoic acid
keywords: Membrane transporter; Perfluoroalkyl acid; Perfluorooctanoate; Rainbow trout; Renal elimination; Tissue distribution