TY - JOUR T1 - COMPARATIVE METABOLISM OF POLYCHLORINATED BIPHENYLS AND TISSUE DISTRIBUTION OF PERSISTENT METABOLITES IN RATS, HAMSTERS, AND GUINEA PIGS JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 373 LP - 380 DO - 10.1124/dmd.104.002444 VL - 33 IS - 3 AU - Koichi Haraguchi AU - Nobuyuki Koga AU - Yoshihisa Kato Y1 - 2005/03/01 UR - http://dmd.aspetjournals.org/content/33/3/373.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -