Comparison of alkylation rates and mutagenicity of directly acting industrial and laboratory chemicals: epoxides, glycidyl ethers, methylating and ethylating agents, halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives.
Groups of industrial and laboratory chemicals were tested for their alkylation activity using 4-(p-nitrobenzyl)-pyridine and deoxyguanosine as nucleophiles. The alkylation activity was compared with mutagenicity of the chemicals to E. coli WP2 uvrA without metabolic activation. All the epoxide-containing compounds including simple epoxides and glycidyl ethers elicited alkylation activity and mutagenicity. Furthermore there was a reasonable correlation between the rate of alkylation and the mutagenic potency. All the methylating and ethylating compounds tested were active but no correlation was observed between the rate of alkylation and the mutagenic potency, apparently due to the different types of alkylation products formed. The other compounds tested including halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives elicited a slow or no alkylation activity while many of the compounds were mutagenic. There was no evidence among the chemicals tested of an alkylating non-mutagen. Thus evidence of alkylation activity appears to indicate mutagenic risk.
D000447:Aldehydes / Q000494:pharmacology; D000477:Alkylating Agents; D000478:Alkylation; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D009153:Mutagens; D013859:Thiocarbamates / Q000494:pharmacology; D013893:Thiram / Q000494:pharmacology
D000447:Aldehydes; D000477:Alkylating Agents; D004852:Epoxy Compounds; D006834:Hydrazines; D006846:Hydrocarbons, Halogenated; D009153:Mutagens; D013859:Thiocarbamates; C020344:glycidyl ethers; D013893:Thiram