| In vitro metabolism of 8-2 fluorotelomer alcohol: interspecies comparisons and metabolic pathway refinement. | |
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MedLine Citation:
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PMID: 17785680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Diane L Nabb; Bogdan Szostek; Matthew W Himmelstein; Michael P Mawn; Michael L Gargas; Lisa M Sweeney; Judith C Stadler; Robert C Buck; William J Fasano |
Publication Detail:
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Type: Comparative Study; Journal Article Date: 2007-09-04 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 100 ISSN: 1096-6080 ISO Abbreviation: Toxicol. Sci. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-16 Completed Date: 2007-12-20 Revised Date: 2010-09-17 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 333-44 Citation Subset: IM |
Affiliation:
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DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714, USA. diane.l.nabb-1@usa.dupont.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Survival Cells, Cultured Cytosol / metabolism Environmental Pollutants / analysis, metabolism Fatty Alcohols / metabolism*, toxicity Fluorocarbons / analysis, metabolism Hepatocytes / drug effects, metabolism* Humans Male Metabolic Networks and Pathways* Mice Mice, Inbred Strains Microsomes, Liver / metabolism* Octanoic Acids / analysis, metabolism Oncorhynchus mykiss Rats Rats, Sprague-Dawley Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/1,1,2,2-tetrahydroheptadecafluorodecanol-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanol; 0/Environmental Pollutants; 0/Fatty Alcohols; 0/Fluorocarbons; 0/Octanoic Acids; 335-67-1/perfluorooctanoic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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