Identification of in Vitro Metabolites of 2, 4, 6, 2', 4', 6'-Hexachlorobiphenyl from Phenobarbital-Treated Dog Liver Microsomes

• Published in: Biological & pharmaceutical bulletin 1993/09/15, Vol.16(9), pp.852-857
• Main Authors: ARIYOSHI, Noritaka, YOSHIMURA, Hidetoshi, OGURI, Kazuta
• Format: Article
• Language: English
• Subjects: 2, 4, 6, 2', 4', 6'-hexachlorobiphenyl; Animals; arene oxide inetermediate; Biological and medical sciences; Chromatography, Gas; dog liver microsome; Dogs; Environmental pollutants toxicology; General aspects; in vitro metabolism; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Medical sciences; Methylation; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Phenobarbital - pharmacology; polychlorinated biphenyl; Polychlorinated Biphenyls - metabolism; secondary metabolism; Toxicology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.16.852

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.