Structure--mutagenicity relationships for chlorinated ethylenes: a model based on the stability of the metabolically derived epoxides.

We have established an empirical structure-activity relationship for the mutagenicity of certain haloalkenes, based on the calculated stability of the corresponding epoxides. The overall form of the relationship can be understood in terms of a simple theoretical model wherein mutagenic activity results from a balance between DNA binding and detoxification by enzymes such as glutathione transferase and epoxide hydrolase. The activity patterns for two different sets of geometries are sufficiently close to support our theoretical model and to suggest that correlations of this type are relatively insensitive to small changes in molecular geometry. Finally, the mutagenic activity for nine other haloalkenes is predicted, based on the present relationships.