Comparative study on formation of hydroxy and sulfur-containing metabolites from different chlorinated biphenyls with 2,5-substitution in rats.

2,4',5-Trichlorobiphenyl (TriCB), 2,3',4',5-tetrachlorobiphenyl (TetraCB), 2,2',4',5,5'-pentachlorobiphenyl (PentaCB), and 2,2',3',4',5,5'-hexachlorobiphenyl (HexaCB) were studied with regard to the fecal excretion and tissue distribution of their metabolites after intraperitoneal injection to rats. Major fecal metabolites were 3- and 4-hydroxy and 3- and 4-methylthio derivatives, the substitution ratios depending largely on the degree of chlorination. As the degree of chlorination increased, hydroxy products were more efficiently excreted, whereas the formation of methylthio metabolites greatly decreased. As a result, the excretion ratios of methylthio and hydroxy products varied with 2.8 for TriCB, 1.3 for TetraCB, 0.04 for PentaCB, and 0.02 for HexaCB. The 3-/4-hydroxy substitution ratios were 0.6 for TriCB, 1.4 for TetraCB, 21 for PentaCB, and 35 for HexaCB, whereas the 3-/4-methythio substitution ratios were 1.2 for TriCB, 0.8 for TetraCB, 0.18 for PentaCB, and 0.12 for HexaCB. The formation rate of 3- and 4-methylthio metabolites from each congener was correlated to the accumulation and distribution of 3- and 4-methylsulfonyl derivatives in tissues. The tissue/blood concentration ratios of methylsulfonyl metabolites showed that the 3-methylsulfonyl derivatives from higher chlorinated biphenyls had a relatively high affinity for liver and adipose tissue, whereas the 4-methylsulfonyl derivatives were selectively retained in the lung in all cases.