Mutagenicity studies with nitrofurans. II. mutagenicity of nitrofurylacrylic acid for Salmonella typhimurium

Abstract

The mutagenicity of 3-(5-nitro-2-furyl)acrylic acid (5-NFA) for Salmonella typhimurium tester strains TA100, TA98, TA1535 and TA1950 was studied by using the spot test, liquid-incubation test, microsomal assay, host-mediated assay and mutagenic analysis of blood and urine from treated mice. 5-NFA was dissolved in physiological saline or 10% ethanol. In the spot test, mutagenicity was found with TA100 and TA98 tester strains. A dose-related increase in mutation frequency was observed in the liquid-incubation test (at concentrations ranging from 1 to 50 micrograms 5-NFA/ml) with TA100 and TA1535; TA100 was the more sensitive. The use of ethanol reduced bacterial cell survival and increased the frequency of revertants. The Salmonella/microsomal assay showed no difference in mutagenic activity between the 5-NFA samples in tests with and without metabolic activation in vitro. In the host-mediated assay, mutagenicity of 5-NFA was detected after its applications in 3 fractionated doses. Subcutaneously applied 5-NFA was mutagenic after a total dose of 15 mg/kg, and after intragastric application of a total dose of 150 mg/kg. When blood samples from treated mice were analysed, the mutagenicity of 5-NFA at intragastric doses of 75, 150 and 300 mg/kg was observed for the tester strains TA100, TA98 and TA1950. The highest frequency of revertants was detected 15 or 30 min after administration of 5-NFA, the level being reached, according to the dose applied and strain used, after 1--2 h and confirmed in the course of 48 h. At the dose of 10 mg/kg, no mutagenic change was observed. Both tests on blood samples and host-mediated assay yielded identical results regardless of whether 5-NFA was dissolved in physiological saline or in 10% ethanol. Experiments in which mutagenic activity in urine was analysed demonstrated the mutagenicity of 5-NFA at the dose of 150 mg/kg with maxima after 24 and 48 h.