Metabolism in Vivo of 3,4,5,3', 4'-Pentachlorobiphenyl and Toxicological Assessment of the Metabolite in Rats
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概要
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Metabolism in vivo of 3,4,5,3', 4'-pentachlorobiphenyl (PenCB) and toxicological assessment of the metabolite were investigated using male Wistar rats. Only one metabolite was isolated from the feces of rats administered 3,4,5,3', 4'-PenCB. By gas chromatography-mass spectrometry, the methylated metabolite was identified with the synthesized authentic sample, 4'-methoxy-3,4,5,3', 5'-PenCB. This indicated that the metabolite was 4'-hydroxy-3,4,5,3', 5'-PenCB, which was produced via a 4', 5'-epoxide formation and subsequent NIH-shift of the 4'-chlorine to the 5'-position. Administration of the metabolite at either single i.p. dose of 3 or 10 mg/kg to rats did not cause any toxic and biological effects such as body weight loss, atrophy of thymus and spleen, liver hypertrophy, increase of liver lipids, or 3-methylcholanthrene-type induction of liver enzymes. These changes were observed in rats administered with 3,4,5,3', 4'-PenCB at a single dose of 3 mg/kg. In addition, a trace amount of 4'-hydroxy-3,4,5,3', 5'-PenCB could be detected in rat liver 5 d after treatment with 3,4,5,3', 4'-PenCB or 4'-hydroxy-3,4,5,3', 5'-PenCB. The amount of this metabolite excreted in feces during 5 d after treatment with 3,4,5,3', 4'-PenCB accounted for only 1.3% of dose. In 4'-hydroxy-3,4,5,3', 5'-PenCB-treated rats, about 60% of dose was excreted as unchanged in feces for 5 d. These results suggest that this metabolite is a detoxified product and has no longer the high affinity for the liver, being excreted rapidly into the feces.
- 公益社団法人日本薬学会の論文
著者
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YOSHIMURA HIDETOSHI
Faculty of Pharmaceutical Sciences, Kyushu University
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Koga Nobuyuki
Faculty Of Pharmaceutical Sciences Kyushu University
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BEPPU Manabu
Faculty of Pharmaceutical Sciences, Kyushu University
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Yoshimura Hidetoshi
Faculty Of Pharmaceutical Sciences Kyushu University
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Beppu M
Faculty Of Pharmaceutical Sciences Kyushu University
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Koga H
Faculty Of Pharmaceutical Sciences Kyushu University(present):department Of Food And Nutrition Nakam
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Beppu Manabu
Faculty Of Pharmaceutical Sciences Kyushu University
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Koga Nobuyuki
Faculty of Nutritional Sciences, Nakamura Gakuen University
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