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Author(s): Nabb DL (Nabb, Diane L.); Szostek B (Szostek, Bogdan); Himmelstein MW (Himmelstein, Matthew W.); Mawn MP (Mawn, Michael P.); Gargas ML (Gargas, Michael L.); Sweeney LM (Sweeney, Lisa M.); Stadler JC (Stadler, Judith C.); Buck RC (Buck, Robert C.); Fasano WJ (Fasano, William J.)
Title: In vitro metabolism of 8-2 fluorotelomer alcohol: Interspecies comparisons and metabolic pathway refinement
Source: TOXICOLOGICAL SCIENCES 100 (2): 333-344
Date: 2007 DEC
Document Type: Journal : Article
DOI: 10.1093/toxsci/kfm230
Language: English
Comment:
Address: DuPont Haskell Lab Hlth & Environm Sci, Newark, DE 19714 USA.
Sapphire Grp Inc, Dayton, OH 45431 USA. Reprint: Nabb, DL, DuPont Haskell Lab Hlth & Environm Sci, H-1-1708, 1090 Elkton
Rd, Newark, DE 19714 USA. E-mail: diane.l.nabb-1@usa.dupont.com
Author Keywords: 8-2 fluorotelomer alcohol; glutathione conjugates; taurine conjugates;
perfluorinated carboxylic acids; perfluorooctanoate; perfluorononanoic
acid; fluorotelomer aldehydes; hepatocytes; hepatic clearance;
microsomes
KeyWords Plus: TELOMER-B ALCOHOL; TOXICOKINETIC MODEL; RATS; LIVER; MICE; HEPATOCYTES;
HUMANS; BIOTRANSFORMATION; ELIMINATION; MICROSOMES
Abstract: The detection of perfluorinated organic compounds in the environment has generated interest in their biological fate. 8-2 Fluorotelomer alcohol (8-2 FTOH, C7F15CF2CH2CH2OH), 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-C-14] 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.
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