Mutagenicity of nifurtimox and benznidazole in the Salmonella/microsome assay.

The genetic activities of two widely used anti-Trypanosoma cruzi drugs, nifurtimox and benznidazole, were investigated. The Salmonella mutagenicity (Ames) test was used to evaluate the mutagenic activity of both drugs. Nifurtimox and benznidazole preferentially induced backward mutations in the base substitution mutagen indicator strain TA100. The observed mutation rates for both drugs were linear over a wide concentration range. Maximum mutagenic activity was obtained at 35 and 100 micrograms per plate for nifurtimox and benznidazole, respectively. No increase in the mutagenic activity of either drug was observed in the presence of rat liver microsomal extracts. Survival experiments revealed that nifurtimox was at least four times more toxic than benznidazole for the Salmonella indicator strain.