The effect of chlorine position on the distribution and excretion of four hexachlorobiphenyl isomers

Abstract

The distribution and excretion of four symmetrical polychlorinated biphenyl (PCB) 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, were studied in the male rat. The study of three of these hexachlorobiphenyl isomers permitted an assessment of the importance of each unchlorinated position in the absence of adjacent unsubstituted carbon atoms on the biphenyl rings. The study of 2,3,6,2′,3′,6′-hexachlorobiphenyl allowed an assessment of the importance of adjacent unsubstituted carbon atoms in an otherwise highly chlorinated PCB. 2,3,6,2′,3′,6′-Hexachlorobiphenyl was rapidly metabolized and excreted relative to the hexachlorobiphenyls which did not have adjacent unsubstituted carbon atoms. The other hexachlorobiphenyls were very slowly metabolized by the male rat and have extremely long half-lives in this species. The results of these studies demonstrate the importance of adjacent unsubstituted carbon atoms to the metabolism of PCBs and imply that when the position of PCB chlorination is such as to inhibit the formation of an arene oxide intermediate then PCB metabolism proceeds very slowly. These studies allo indicate that in the absence of adjacent unsubstituted carbon atoms, the preferred mechanism of PCB metabolism may be by the insertion of a hydroxyl group at the meta position.