ToxSci Advance Access originally published online on May 11, 2005
Toxicological Sciences 2005 86(2):231-238; doi:10.1093/toxsci/kfi191
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Induction of Hepatic Peroxisome Proliferation by 8–2 Telomer Alcohol Feeding In Mice: Formation of Perfluorooctanoic Acid in the Liver
* Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1–1, Sakado, Saitama 350-0295, Japan, and Research and Development Laboratories, Maruho Co., 1 Awatacho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan
Received January 9, 2005; accepted May 2, 2005
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.
Key Words: 8–2 telomer alcohol; perfluorooctanoic acid; peroxisome proliferation; liver; mouse.
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