Document Detail


In vitro metabolism of 8-2 fluorotelomer alcohol: interspecies comparisons and metabolic pathway refinement.
MedLine Citation:
PMID:  17785680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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:
Type:  Comparative Study; Journal Article     Date:  2007-09-04
Journal Detail:
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:
Created Date:  2007-11-16     Completed Date:  2007-12-20     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  333-44     Citation Subset:  IM    
Affiliation:
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714, USA. diane.l.nabb-1@usa.dupont.com
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MeSH Terms
Descriptor/Qualifier:
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:
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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