RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 373
OP 380
DO 10.1124/dmd.104.002444
VO 33
IS 3
A1 Haraguchi, Koichi
A1 Koga, Nobuyuki
A1 Kato, Yoshihisa
YR 2005
UL http://dmd.aspetjournals.org/content/33/3/373.abstract
AB 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