10 aryl propylene oxides and 6 aryl butylene oxides were synthesized. Dose-mutagenicity relationships were studied for these compounds and for 1,2-epoxybutane, using both the preincubation and plate incorporation Ames tests with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined by concurrent testing at single doses with the plate incorporation assay in strain TA100. In both series of compounds, mutagenicity showed very correlation to chemical reactivity, molar volume and partition values. However, all compounds were mutagenic in at least one system with the propylene oxides being more mutagenic than the corresponding butylene oxide derivatives. The naphthyl derivatives in each series were the most mutagenic.

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.

In an extension of previous studies with deoxycytidine and thymidine reactivities, propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide were reacted with deoxyguanosine as well as deoxyadenosine and, except for the trichloro compound, with DNA. Reactivity with the purine deoxynucleosides as well as the four deoxynucleosides in DNA were quantitated by HPLC methods. Correlations were found for the reactivity with individual deoxynucleosides in solution to Taft sigma electron-withdrawing values of the substituents on the epoxides and for reaction with model nucleophiles. In general, these correlations were not as pronounced for the reactivities of the propylene oxides with the nucleosides in DNA. Correlations for reactivity of the propylene oxides with the individual deoxynucleosides in solution and in DNA, except for dThd, were indicated for mutagenicity in TA100 in the liquid-preincubation Ames test. However, this was not the case for mutagenicities determined with the plate incorporation procedure nor with TA1535, where the relative mutagenicity of trichloropropylene oxide was the outstanding difference. Trichloropropylene oxide appeared to depend upon the error-prone system in TA100 for full expression of its mutagenicity.

6 aromatic glycidyl ethers containing naphthyl, biphenyl or benzylphenyl substituents were synthesized. These epoxides together with the commercially available compounds 2-biphenylyl glycidyl ether were examined for dose-mutagenicity relationships using the plate incorporation Ames test with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined for these compounds and 3 phenyl glycidyl ethers by concurrent testing at a single dose with strain TA100. Meaningful correlations could not be established for the mutagenicity of these epoxides to their molecular volumes, partition values, nor to their reactivities with the model nucleophile, 4-(4-nitrobenzyl) pyridine. However, it was noted that increased conjugated aromatic unsaturation with its resulting planarity led to increased mutagenicity and that this effect decreased when it was further removed from the epoxide moiety.