Species difference in hydroxylation of polychlorinated biphenyls and exposure of metabolites in human blood.

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1. In the hydroxylation metabolism of polychlorinated biphenyls (PCBs), species differences were studied in rats, mice, hamsters and guinea pigs dosed with PCB mixture (Kanechlor 500). Catechol PCBs (mainly di0H-CBH0) were highly produced in hamsters, while hydroxylated PCBs (mainly 4-OH-CB 107) and methylsulfonyl PCBs were preferably produced in rats and mice. Guinea pigs produced methylsulfonyl-hydroxylated PCBs. All diOH-PCBs were found to be derived from 2,5-or 2,3,6-chlorinated PCBs.2. The in vitro metabolism of PCB 101 was studied using liver microsomes of rats, hamsters and guinea pigs.3-0H-, 3'-OH-, 4'-OH-and 3',4'-di0H-CB101 were formed by liver microsomes of rats and guinea pigs. The formation of di0H-CB101 from 3'-OH-and 4'-0H-CB101 proceeded at much higher rate than that from CB101 and was accelerated by phenobarbital-treatment. The result indicated that the metabolism of CB 101 to di0H-CB101 is principally catalyzed by CYP2B enzymes, which prefer 4'-0H-and 3'-OH to CB101.3. Hydroxyl Ted PCBs retained in human blood were found to be 4-0H-CB107, 4-0H-CB146 and 4-0H-CB187.In order to further investigate the body burden of di0H-PCBs in human, blood samples from Fukuoka residents were analyzed by electron capture negative ionization-gas chromatography-mass spectrometry (ECNI-GC), using 18 synthesized references (veratrolic PCBs) for catechol metabolites. As a result, one di0H-PCB was detected in human blood, and identified as 4,5-(OH)_2-2,3,6,2',4',5'-hexaCB (di0H-CB149).Further monitoring and toxicological significance of hydroxylated PCBs including catecholic PCBs should be performed, since these metabolites may decrease the thyroxine levels in human body.