Vinyl chloride mutagenicity via the metabolites chlorooxirane and chloroacetaldehyde monomer hydrate.
Mutagenicity tester strains of Bacillus and Salmonella were used to assay vinyl chloride in nutrient broth at a practical concentration level. Also screened without exogenous activation were seven potential metabolites of vinyl chloride in their pure forms as well as the related epichlorohydrin. Chlorooxirane, chloroacetaldehyde, chloroacetaldehyde monomer hydrate, chloroacetaldehyde dimer hydrate, chloroacetaldehyde trimer, and epichlorohydrin produced significant mutagenic acitivity in Salmonella typhimurium strains sensitive to base-pair mutation. A recombination repair deficient strain of Bacillus subtilis was inhibited in growth by these compounds, whereas excision repair deficient and wild type strains of Bacillus subtilis were relatively unaffected. On the basis of these assays a working hypothesis for the vinyl chloride carcinogenesis mechanism is proposed which involves chlorooxirane and chloroacetaldehyde monomer hydrate as the ultimate carcinogenic metabolites of vinyl chloride.
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects*; D002273:Carcinogens / Q000494:pharmacology; D002728:Chlorohydrins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004811:Epichlorohydrin / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005027:Ethylene Oxide / Q000494:pharmacology / Q000031:analogs & derivatives; D008956:Models, Chemical; D009153:Mutagens; D009154:Mutation / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects*; D013045:Species Specificity; D014752:Vinyl Chloride / Q000378:metabolism / Q000494:pharmacology*; D014753:Vinyl Compounds / Q000494:pharmacology*
D002273:Carcinogens; D002728:Chlorohydrins; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; D014753:Vinyl Compounds; D004811:Epichlorohydrin; D005023:Ethylene Chlorohydrin; C015061:chloroethylene oxide; D000079:Acetaldehyde; D005027:Ethylene Oxide; D014752:Vinyl Chloride