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ToxSci Advance Access published online on September 4, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm230
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

In-Vitro Metabolism of 8-2 Fluorotelomer Alcohol: Interspecies Comparisons and Metabolic Pathway Refinement

Diane L. Nabb1,*, Bogdan Szostek*, Matthew W. Himmelstein*, Michael P. Mawn*, Michael L. Gargas{dagger}, Lisa M. Sweeney{dagger}, Judith C. Stadler*, Robert C. Buck* and William J. Fasano*

* DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714 {dagger} The Sapphire Group, Inc., Dayton, Ohio 45431

1 To whom correspondence should be addressed. Office: (302) 451-4716. E-mail: diane.l.nabb-1{at}usa.dupont.com, Express Delivery: DuPont Haskell Laboratory H-1/1708, 1090 Elkton Rd. Newark DE 19714

Received May 18, 2007; revision received August 3, 2007; accepted August 25, 2007


  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 perfluroocatanoic acid (PFOA) in the environment. In this study, the in vitro metabolism of [3-14C] 8-2 FTOH and selected acid metabolites by rat, mouse, trout, and human hepatocytes and by rat, mouse, and human liver microsomes and cytosol was 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 were 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.

Key Words: 8-2 fluorotelomer alcohol; glutathione conjugates; taurine conjugates; perfluorinated carboxylic acids; perfluorooctanoate; perfluorononanoic acid; fluorotelomer aldehydes; hepatocytes; hepatic clearance; microsomes.

Author email addresses: diane.l.nabb-1{at}usa.dupont.com, bogdan.szostek{at}usa.dupont.com, matthew.w.himmelstein{at}usa.dupont.com, michael.p.mawn{at}usa.dupont.com, mlg{at}thesapphiregroup.com, lms{at}thesapphiregroup.com, judy.stadler{at}usa.dupont.com, robert.c.buck{at}usa.dupont.com, william.j.fasano{at}usa.dupont.com


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