title: In vitro metabolism of 8-2 fluorotelomer alcohol: interspecies comparisons and metabolic pathway refinement.
abstract: The detection of perfluorinated organic compounds in the environment has generated interest in their biological fate. 8-2 Fluorotelomer alcohol (8-2 FTOH, C(7)F(15)CF(2)CH(2)CH(2)OH), a raw material used in the manufacture of fluorotelomer-based products, has been identified in the environment and has been implicated as a potential source for perfluorooctanoic acid (PFOA) in the environment. In this study, the in vitro metabolism of [3-(14)C] 8-2 FTOH and selected acid metabolites by rat, mouse, trout, and human hepatocytes and by rat, mouse, and human liver microsomes and cytosol were investigated. Clearance rates of 8-2 FTOH in hepatocytes indicated rat > mouse > human >/= trout. A number of metabolites not previously reported were identified, adding further understanding to the pathway for 8-2 FTOH metabolism. Neither perfluorooctanoate nor perfluorononanoate was detected from incubations with human microsomes. To further elucidate the steps in the metabolic pathway, hepatocytes were incubated with 8-2 fluorotelomer acid, 8-2 fluorotelomer unsaturated acid, 7-3 acid, 7-3 unsaturated acid, and 7-2 secondary fluorotelomer alcohol. Shorter chain perfluorinated acids were only observed in hepatocyte and microsome incubations of the 8-2 acids but not from the 7-3 acids. Overall, the results indicate that 8-2 FTOH is extensively metabolized in rats and mice and to a lesser extent in humans and trout. Metabolism of 8-2 FTOH to perfluorinated acids was extremely small and likely mediated by enzymes in the microsomal fraction. These results suggest that human exposure to 8-2 FTOH is not expected to be a significant source of PFOA or any other perfluorocarboxylic acids.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714, USA. diane.l.nabb-1@usa.dupont.com
authors.forename: Diane L
authors.initials: DL
authors.lastname: Nabb
authors.forename: Bogdan
authors.initials: B
authors.lastname: Szostek
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Himmelstein
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mawn
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gargas
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sweeney
authors.forename: Judith C
authors.initials: JC
authors.lastname: Stadler
authors.forename: Robert C
authors.initials: RC
authors.lastname: Buck
authors.forename: William J
authors.initials: WJ
authors.lastname: Fasano
mesh_terms: D000818:Animals; D002210:Caprylates / Q000032:analysis / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004785:Environmental Pollutants / Q000032:analysis / Q000378:metabolism; D005233:Fatty Alcohols / Q000378:metabolism* / Q000633:toxicity; D005466:Fluorocarbons / Q000032:analysis / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism*; D017686:Oncorhynchus mykiss; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity