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ToxSci Advance Access published online on May 11, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi191
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 9, 2005
Accepted May 2, 2005

Biotransformation and Toxicokinetics

Induction of hepatic peroxisome proliferation by 8-2 telomer alcohol feeding in mice: Formation of perfluorooctanoic acid in the liver

Naomi Kudo 1*, Yuko Iwase 1, Hiroshi Okayachi 2, Yoshihiro Yamakawa 2, and Yoichi Kawashima 1

1 Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan
2 Research and Development Laboratories, Maruho Co., 1 Awatacho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan

* To whom correspondence should be addressed.
Naomi Kudo, E-mail: naokudo{at}josai.ac.jp


  Abstract

The effects of dietary administration of 1H, 1H, 2H, 2H-perfluorodecanol (8-2 telomer alcohol), on peroxisome proliferation in the liver of mice were studied. Male ddY mice were fed on a diet containing 8-2 telomer alcohol at concentrations of 0, 0.025, 0.05, 0.1 and 0.2% (w/w) for 7, 14, 21 and 28 days. These treatments with 8-2 telomer alcohol caused liver enlargement in a dose- and duration-dependent manner. Peroxisome proliferation in the liver of mice was confirmed by electron microscopic examination. Peroxisomal acyl-CoA oxidase was induced by these treatments with 8-2 telomer alcohol in a dose- and time-dependent manner. The concentration of perfluorooctanoic acid (PFOA) and related compounds were determined in the liver and plasma, since PFOA had been shown to be a possible metabolite of 8-2 telomer alcohol and to cause significant peroxisome proliferation in rodents. Five metabolites, namely, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), 2H, 2H-perfluorodecanoic acid (8-2 telomer acid), and two unidentified metabolites, were present in the liver and serum. PFOA was confirmed to be accumulated in the liver of mice following the administration of 8-2 telomer alcohol in a dose- and duration-dependent manner. A linear relationship was observed between the concentration of PFOA and the activity of peroxisomal acyl-CoA oxidase in the liver of mice. These results strongly suggest that PFOA, but not 8-2 telomer alcohol itself, caused peroxisome proliferation in the liver. The present study provided evidence that 8-2 telomer alcohol is converted into PFOA in vivo and that the PFOA formed produces biological effects in the liver of mice.

Keywords: 8-2 telomer alcohol; perfluorooctanoic acid; peroxisome proliferation; liver; mouse.
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