The comparative genotoxicological study of new local anesthetics, 3-(2-alkoxyphenylcarbamoyloxy)quinuclidium chlorides, on Salmonella typhimurium, Saccharomyces cerevisiae, Vicia faba, Hordeum vulgare and Drosophila melanogaster

Potential gentoxicity of five new local anesthetics, derivatives of phenylcarbamic acid differing in the length of the alkyl chain of the alkoxy substituent, was studied on five test systems. There was a direct relationship with increased toxic effect in bacteria and yeast as a function of the elongation of the alkyl chain of the alkoxy substituents of the phenylcarbamic acid esters. On the other hand, no structure-toxicity relationship was found after application of 3-(2-alkoxyphenylcarbamoyloxy)-quinuclidium chlorides on plants and Drosophila. All anesthetics were nonmutagenic to Salmonella typhimurium strains TA97, TA98, TA100, and TA102 in the absence and in the presence of S9 mix. Pentyloxy and heptyloxy derivatives increased rates of genetic changes in Saccharomyces cerevisiae, mainly revertants at the isoleucine locus. Pentyloxy and hexyloxy derivatives increased the frequency of chromosome aberrations in Vicia faba root-tip meristems. No chlorophyll mutations were detected after treatment of Hordeum vulgare with pentyloxy, hexyloxy and heptyloxy derivatives. No sex-linked recessive lethals were scored in Drosophila melanogaster males. The rates of aneuploids induced in their germ cells were significantly increased after treatment with butoxy and octyloxy derivatives. However, the local toxic and genotoxic effects of test anesthetics on the microorganisms of the anesthetized tissues may be of some importance. In particular, the genotoxic effect exhibited in fungi by the heptyloxy derivative, a potent local anesthetic, was remarkable.