Induction of hepatic peroxisome proliferation by 8-2 telomer alcohol feeding in mice: formation of perfluorooctanoic acid in the liver.
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.
Kudo
Naomi
N
Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan. naokudo@josai.ac.jp
Iwase
Yuko
Y
Okayachi
Hiroshi
H
Yamakawa
Yoshihiro
Y
Kawashima
Yoichi
Y
D042962:Acyl-CoA Oxidase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002210:Caprylates / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D003652:Decanoic Acids / Q000138:chemical synthesis; D005466:Fluorocarbons / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020025:Peroxisome Proliferators / Q000378:metabolism*; D020675:Peroxisomes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D002210:Caprylates; D003652:Decanoic Acids; D005466:Fluorocarbons; D020025:Peroxisome Proliferators; C033729:fluorotelomer alcohols; C036567:perfluorodecanoic acid; C023036:perfluorooctanoic acid; D042962:Acyl-CoA Oxidase