Epoxidation of the lindane metabolite, beta-PCCH, by human- and rat-liver microsomes.
Human- and rat-liver microsomes convert the lindane metabolite, beta-PCCH (beta-1,3,4,5,6-pentachlorocyclohex-1-ene (3,4,6/5-PCCH] to the metabolites: 1,2,4-TCB (1,2,4-trichlorobenzene), 1,2,3,4-TTCB (1,2,3,4-tetrachlorobenzene), 2,4,5-TCP (2,4,5-trichlorophenol), 3,4,5/6-PCCOL (1,2,4,5,6-pentachlorocyclohex-1-en-3-ol) and beta-PCCH oxide (1,2,3,4,5-pentachloro-7-oxabicyclo[4.1.0]heptane) or (3,4,6/5-PCCH oxide). The identity of the beta-PCCH oxide is confirmed by column chromatography and g.l.c.-mass spectrometry, in comparison to characterized synthetic material. The stability of the beta-PCCH oxide is indicated by its resistance to hydrolysis by microsomal epoxide hydrolase (EC. 3.3.2.3), or various aqueous acid conditions. It shows no mutagenicity using S. typhimurium strain TM677. However, in levels above 0.05 mg/ml it was lethal to the test cells. It is not a substrate for and is only a weak inhibitor of epoxide hydrolase. A stable halogenated hydrocarbon epoxide metabolite is described. Its toxicological role, if any, remains unaccounted for.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D001556:Hexachlorocyclohexane / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; C010275:pentachlorocyclohexene; D001556:Hexachlorocyclohexane; C043572:1,3,4,5,6-pentachlorocyclohexene-1-oxide