Hydroxylation and methylthiolation of mono-ortho-substituted polychlorinated biphenyls in rats: identification of metabolites with tissue affinity.

The metabolism of three mono-ortho-substituted congeners, 2,3,3',4, 4'-pentachlorobiphenyl (CB105), 2,3',4,4',5-pentachlorobiphenyl (CB118), and 2,3,3',4,4',5-hexachlorobiphenyl (CB156), was investigated with regard to the identification of hydroxy- and sulfur-containing metabolites and their tissue retention in rats. Hydroxylation proceeded primarily at the meta or para position either via an arene oxide, involving NIH shift and dechlorination, or by direct insertion of a hydroxyl group. CB105 was hydroxylated preferably in the 2,3,4-trichlorinated ring to yield 4-OH-2,3,3',4', 5-pentaCB, whereas CB118 was hydroxylated in the 2,4, 5-trichlorinated ring to yield the same hydroxy metabolite to a similar extent. The concentration of 4-OH-2,3,3',4',5-pentaCB in blood was >3 times higher than that in liver, lung, or kidney. The ratios of 4-OH-2,3,3',4',5-pentaCB to unchanged CB in blood were 11:1 for CB105 and 7:1 for CB118. The other two metabolites, 4'-OH-2, 3',4,5,5'-pentaCB from CB118 and 4'-OH-2,3,3',4,5,5'-hexaCB from CB156, also exhibited a high blood affinity. Another metabolism of mono-ortho-PCBs PCBs involved methylthiolation in the vicinal ortho and meta unsubstituted positions to give methylthio metabolites, which were detected as methylsulfonyl metabolites in liver and adipose tissue. The tissue retention of these metabolites might contribute to the toxic and biologic effects of mono-ortho-substituted PCBs.