Mutagenicity of para-substituted [alpha]-methylstyrene oxide derivatives with Salmonella

Abstract

A series of 5 para-substituted [alpha]-methylstyrene oxide derivatives have been synthesized and together with [alpha]-methylstyrene oxide as well as styrene oxide have been studied as to their mutagenicity with the TA100 and TA1535 strains of Salmonella typhimurium. A multiple regression analysis model has been developed which describes the mutagenicity of the [alpha]-methylstyrene oxides in TA100. An increase in van der Waals volume was the most important variable in the model with greater improvement occurring with inclusion of the Hammett values for the para substituents on the compounds. The [alpha]-methylstyrene oxides were less active alkylating agents with 4-(p-nitrobenzyl)pyridine than styrene oxide and with pyridine all reactivity was at the [beta]-epoxide carbon. However all the [alpha]-methylstyrene oxide derivatives, except for the bromo compound where toxicity was evident, showed mutagenicity values either greater or comparable to that of styrene oxide. These studies would indicate that reactivity at the [beta]-carbon should also be a factor in describing the mutagenicity of the parent styrene oxide series.