Mutagenic activity of acetonitrile and fumaronitrile in three short term assays with special reference to...

Two aliphatic nitriles, acetonitrile and fumaronitrile were tested for their genotoxic potential in three mutagenicity test systems: the Salmonella/microsome-assay, an assay using Saccharomyces cerevisiae (strain D7), and the bone marrow micronucleus test. Both compounds were tested with and without metabolic activation in the yeast and the bacterial test systems using S9 preparations from phenobarbitone-pretreated and autoinduced rats. Autoinduction was performed by chronic (7 days) application of a dose equivalent to a 5% oral LD50-value of the respective compound. With yeast strain D7 both nitriles induced low levels of gene conversion in the presence of phenobarbitone-induced liver homogenate. An increase in the number of ile+-revertants was not detectable under any condition. Neither of the compounds showed mutagenic activity in the Ames test with or without metabolic activation. A weak positive effect of acetonitrile could be detected in the micronucleus test 24 h after i.p.-injection of the compound using a dose of 60% LD50. Fumaronitrile showed positive results with a 50% LD50 dose 48 h after administration to mice not preinduced. After 1 week of autoinduction these effects did not appear anymore, with the exception of acetonitrile 72 h after application of a dose amounting to 60% of the oral LD50-value.