Herbicidal phenylalkylureas as possible mutagens

摘要: Abstract The herbicide monuron ( N -(4-chlorophenyl)- N′ , -dimethylurea)—a recognized carcinogen—and some of its congeners have been found also to induce back mutations in Salmonella typhimurium (Ames test), as well micronuclei mouse bone marrow cells and an inhibition testicular DNA synthesis (DSI test) mice. As both the Ames test DSI correlate with chemical carcinogenicity, urea herbicides general might be suspected carcinogenic activity. In order investigate potential mode action these substances we looked for possible activation mechanisms. reaction sequence N-oxidation-esterification-carbonium ion formation seemed only one able fit observed structure-activity relationships. Chemical proposed -acetoxy compounds provided means testing this hypothesis. Only -acetoxy-, but neither -hydroxy- nor unchanged parent ureas, exhibited a direct alkylating measured by NBP-assay. reactivity pattern several positional isomers could shown coincide theoretical predictions, did stability chloroisomers aqueous solution at pH 7. Furthermore derivatives demonstrated behave directly acting mutagens, while activity is dependent on metabolic S-9-liver fraction. enhancing Acetyl-CoA S-9 mediated mutagenicity ureas can then regarded final proof sequence.