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 Drosphila 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.