Examination of the mutagenicity of RDX and its N-nitroso metabolites using the Salmonella reverse mutation assay

The mutagenicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its N-nitroso derivatives hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) were evaluated using the Salmonella tryphimurium reverse mutation assay (Ames assay) with strains TA97a, TA98, TA100, and TA102. Using a preincubation procedure and high S9 activation (9%), RDX was observed to induce weak mutagenesis to strain TA97a with a mutagenicity index (MI) of 1.5–2.0 at a dose range of 32.7–1090 μg/plate. MNX induced moderate mutagenesis to strain TA97a with an MI of 1.6–2.8 at a dose range of 21.7–878 μg/plate. TNX also induced moderate mutagenesis in strain TA97a with an MI of 2.0–3.5 to TA97a at a dose range of 22.7–1120 μg/plate. TNX also caused weak mutagenesis to strain TA100 with S9 activation at the dose of 1200 μg/plate. MNX and TNX induced weak to moderate mutagenesis to strain TA102. Strain TA97a was found to be the most sensitive strain among these four strains. No cytotoxicity of RDX, MNX, and TNX was observed at the concentrations used in this study. Doses were verified by HPLC.