Propane 2-nitronate is the major genotoxic form of 2-nitropropane

The mutagenicity of 2-nitropropane in Salmonella typhimurium (strain TA100) was proportional to the pH (range 6.1-9.1) of the medium used for pre-incubation of the agent and for incubation of the agent with the Salmonella. The mutagenicity correlated with an enhanced rate of tautomerase to propane 2-nitronate at relatively high pH as measured by high performance liquid chromatography. Both the mutagenicity in Salmonella typhimurium (strains TA100 and TA102) and the rate of tautomerisation to the nitronate was lower with 2-deutero-2-nitropropane than with non-deuterated 2-nitropropane. Furthermore, 2-deutero-2-nitropropane was less potent in the induction of unscheduled DNA synthesis in rat hepatocytes over a 4-h period. Propane 2-nitronate therefore appears to be pivotal in the causation of the genetic toxicity of 2-nitropropane. The presence of hepatocytes enhanced nitronate production from 2-nitropropane suggesting a contribution from hepatic enzymes in the tautomerisation reaction.