MUTAGENICITIES OF SAFROLE, ESTRAGOLE, EUGENOL, TRANS-ANETHOLE, AND SOME OF THEIR KNOWN OR POSSIBLE METABOLITES FOR SALMONELLA-TYPHIMURIUM MUTANTS

Safrole, estragole, anethole, and eugenol and some of their known or possible metabolites were tested for mutagenic activity for S. typhimurium TA1535, TA100, and TA98. Highly purified 1′-hydroxyestragole and 1′-hydroxysafrole were mutagenic (approximately 15 and 10 revertants/μmole, respectively) for strain TA100 in the absence of fortified liver microsomes; trans-anethole and estragole appeared to have very weak activity. 3′-Hydroxyanethole was too toxic for an adequate test. Supplementation with NADPH-fortified rat-liver microsomes and cytosol converted 3′-hydroxyanethole to a mutagen(s) and increased the mutagenic activities for strain TA100 of 1′-hydroxyestragole, 1′-hydroxysafrole, estragole, and anethole. No mutagenicity was detected for safrole or eugenol with or without added NADPH-fortified liver preparations. The electrophilic 2′,3′-oxides of safrole, 1′-hydroxysafrole, 1′-acetoxysafrole, 1′-oxosafrole, estragole, 1′-hydroxyestragole, and eugenol showed dose-dependent mutagenic activities for strain TA1535 in the absence of fortified liver microsomes. These mutagenic activities ranged from about 330 revertants/μmole for 1′-oxosafrole-2′,3′-oxide to about 7000 revertants/μmole for safrole-2′,3′-oxide. The arylalkenes, their hydroxylated derivatives, or their epoxides did not show mutagenic activity for strain TA98, except for 1′-oxosafrole-2′,3′-oxide, which had weak activity. Since the arylalkenes are hydroxylated and/or epoxidized by hepatic microsomes, hydroxy and epoxide derivatives appear to be proximate and ultimate mutagenic metabolites, respectively, of the arylalkenes. © 1979.