title: The mutagenicity of chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid, conceivable metabolites of vinyl chloride.
abstract: Previous investigations have shown that the carcinogen vinyl chloride causes base-pair substitution in the bacterium Salmonella typhimurium. The ability of four conceivable metabolites-chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid-to cause base-pair substitution directly in Salmonella typhimurium TA1535 has been compared. The main comparison was performed at initial concentrations from 0.1 to 1.5 mM. In this region, however, a mutagenic effect was observed only with chloroethylene oxide and chloroacetaldehyde, the former being approximately 20 times more effective than the aldehyde when compared on a molar basis.2-Chloroethanol and chloroacetic acid were studied also at higher concentration (1 mM-1 M), and a weak mutagenic response was found with 1 M 2-chloroethanol solution. With chloroacetic acid no enhancement of the mutation frequency could be detected. Chloroethylene oxide was found to be approximately 450 times more effective as a mutagen than chloroacetaldehyde when the comparison is based on exposure doses, defined as the time-dependent concentrations of the compounds in the treatment solutions, integrated between the times of onset and termination of treatment. Similarly, chloroethylene oxide was 10,000-15,000 times more effective as a mutagen than ethylene oxide, used as a positive control.
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009154:Mutation; D010087:Oxides / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014752:Vinyl Chloride / Q000378:metabolism* / Q000494:pharmacology*; D014753:Vinyl Compounds / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000085:Acetates; D010087:Oxides; D014753:Vinyl Compounds; D000431:Ethanol; D000079:Acetaldehyde; D014752:Vinyl Chloride