Tissue Distribution of Methylsulfonyl Metabolites Derived from 2,2′,4,5,5′-Penta- and 2,2′,3,4′,5′,6-Hexachlorobiphenyls in Rats

Abstract.

The time courses of fecal excretion and tissue distribution of metabolites derived from 2,2′,4,5,5′-pentachlorobiphenyl (CB101) and 2,2′,3,4′,5′,6-hexachlorobiphenyl (CB149) were investigated in male Wistar rats. The metabolism of both congeners involved primarily hydroxylation at the 3-position, and methylthiolation at the 4-position. Metabolites distributed in tissue were dominated by different ratios of 3- and 4-methylsulfonyl (MeSO₂) metabolites. The 3-/4-MeSO₂ metabolite ratios in liver and adipose tissue for both congeners were 0.41–0.61 at day 4, and then increased to 0.85–1.00 for up to day 42. In contrast, the ratios in lung were 0.03–0.04, and then decreased to 0.01. Compared to the unchanged PCBs at day 42, the distribution ratios of 3-MeSO₂ metabolites were greater in the order of liver (0.46 for CB101 and 0.21 for CB149) > kidney > blood > lung > adipose tissue, whereas those of 4-MeSO₂ metabolites were in the order of lung (9.50 for CB101 and 4.00 for CB149) > kidney > blood > liver > adipose tissue, indicating the different binding affinity of 3-MeSO₂ metabolites in liver from that of 4-MeSO₂ metabolites in lungs of rats. Furthermore, the structure-tissue affinity relationship for 3-MeSO₂ metabolites was investigated, following the administration of 11 3-MeSO₂-PCB congeners to rats. The results indicated that the retention potential of 3-MeSO₂ metabolites in the liver largely depends on the ortho-chlorine substitution in the biphenyl ring rather than the degree of chlorination.