Identification of in vitro metabolites of 2,4,6,2′,4′,6′-hexachlorobiphenyl from phenobarbital-treated dog liver microsomes

We studied in vitro metabolites of 2, 4, 6, 2′, 4′, 6′-hexachlorobiphenyl (HCB, IUPAC PCB No. 155) produced by liver microsomes of a phenobarbital (PB)-treated beagle dog. The major metabolites were 3-hydroxy-2, 4, 6, 2′, 4′, 6′-HCB (M-1), 4-hydroxy-2, 6, 2′, 4′, 6′-pentachlorobiphenyl (PenCB, M-2) and 3, 4-dihydroxy-2, 6, 2′, 4′, 6′-PenCB (M-3). Furthermore, 4-hydroxy-2, 3, 6, 2′, 4′, 6′-HCB (M-4), which could be formed via the 3, 4-epoxidation and the subsequent NIH-shift of the chlorine from the 4 to the 3 position, was also detected. We found that M-3 is a common secondary metabolite of the two major monohydroxy metabolites, M-1 and M-2. These results indicate that the dog seems to metabolize and eliminate this congener not only by a mechanism involving direct insertion of a hydroxyl group but also via an arene oxide intermediate.