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.
Ariyoshi
N
N
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yoshimura
H
H
Oguri
K
K
D000818:Animals; D002849:Chromatography, Gas; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*
D011078:Polychlorinated Biphenyls; C027310:2,4,6,2',4',6'-hexachlorobiphenyl; D010634:Phenobarbital