The mutagenicity of chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid, conceivable metabolites of vinyl chloride

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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.

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