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Drug Metabolism and Disposition Fast Forward
First published on December 17, 2004; DOI: 10.1124/dmd.104.002444

0090-9556/05/3303-373-380$20.00
DMD 33:373-380, 2005

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*POLYCHLORINATED BIPHENYLS

COMPARATIVE METABOLISM OF POLYCHLORINATED BIPHENYLS AND TISSUE DISTRIBUTION OF PERSISTENT METABOLITES IN RATS, HAMSTERS, AND GUINEA PIGS

Koichi Haraguchi, Nobuyuki Koga, and Yoshihisa Kato

Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan (K.H.); Department of Food and Nutrition, Nakamura Gakuen University, Fukuoka, Japan (N.K.); and School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan (Y.K.)

The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4- or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO2-CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO2-CBs from 2,5-dichloro-substituted PCBs, guinea pigs formed higher levels of meta-MeSO2-CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3',4'-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2',4'-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO2- and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.

Address correspondence to: Dr. Koichi Haraguchi, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan. E-mail: ko-ichi{at}ka2.so-net.ne.jp




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Y. Kato, S.-i. Ikushiro, R. Takiguchi, K. Haraguchi, N. Koga, S. Uchida, T. Sakaki, S. Yamada, J. Kanno, and M. Degawa
A Novel Mechanism for Polychlorinated Biphenyl-Induced Decrease in Serum Thyroxine Level in Rats
Drug Metab. Dispos., October 1, 2007; 35(10): 1949 - 1955.
[Abstract] [Full Text] [PDF]


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