Metabolism of symmetrical hexachlorobiphenyl isomers in the rat

Abstract

The excretion and metabolism of four symmetrical hexachlorobiphenyl [ 14C] isomers 2,3,5,2′,3′,5′-hexa-; 2,3,6,2′,3′,6′-hexa-; 2,4,5,2′,4′,5′-hexa-; and 2,4,6,2′,4′,6′-hexachlorobiphenyl, have been studied in the rat. Excretion of these hexachlorobiphenyl prior to metabolism to more polar compounds was negligible. Of the four isomers studied, the three which do not have vicinal unsubstituted carbon atoms were metabolized and excreted quite slowly. One isomer, 2,3,6,2′,3′,6′-hexachlorobiphenyl, which does have vicinal unsubstituted carbon atoms, was rapidly metabolized and excreted. The results indicate that the rate of metabolism and excretion of these hexachlorobiphenyl isomers depends on the position rather than the degree of chlorine substitution on the biphenyl ring. Metabolites of these hexachlorobiphenyl isomers were isolated from rat feces and identified by comparison of their mass and NMR spectral and chromatographic properties with synthetic metabolites. The hexachlorobiphenyl metabolites showed evidence of dechlorination, chlorine shifts, and possible metabolism via the direct insertion of a hydroxyl group. The nature of the metabolites of these hexachlorobiphenyl isomers strongly supports the intermediacy of an arene oxide as the predominant mechanism of PCB metabolism. Metabolism by direct insertion of a hydroxyl group is of importance only in the absence of vicinal unsubstituted carbon atoms and is facilitated by the presence of unchlorinated meta positions.