Genotoxicity of allyl compounds--a quick screening strategy based on structure-activity relationships and a battery...

A proposed strategy for the rapid screening of the genotoxic activities of allylic compounds is based on structure-activity relationships elaborated by a battery of quick screening tests. The procedure facilitates the selection of appropriate representatives of this class of compound for subsequent testing, so that both expensive and time-consuming assays and the use of animals can be drastically reduced. The studies have yielded several important results. Allylic compounds with suitable leaving groups have been shown to exert direct genotoxic activity. In the metabolic activation of these compounds the formation of epoxides is clearly of minor importance, playing a role only in the case of 2,3-dichloro-1-propene and some of its homologues, whereas all reactive allylic compounds can be activated to genotoxic alpha,beta-unsaturated carbonyl compounds (acrolein). The most significant factors for genotoxicity are the leaving groups and halogen substituents. Alkyl substituents increase the direct genotoxicity while decreasing the indirect activity (via acroleins).