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 32.7-1090microg/plate. MNX induced moderate mutagenesis to strain TA97a with an MI of 1.6-2.8 at a dose range of 21.7-878microg/plate. TNX also induced moderate mutagenesis in strain TA97a with an MI of 2.0-3.5 to TA97a at a dose range of 22.7-1120microg/plate. TNX also caused weak mutagenesis to strain TA100 with S9 activation at the dose of 1200microg/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.
Pan
Xiaoping
X
The Institute of Environmental and Human Health (TIEHH), Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409-1163, USA. xiaoping.pan@tiehh.ttu.edu
San Francisco
Michael J
MJ
Lee
Crystal
C
Ochoa
Kelly M
KM
Xu
Xiaozheng
X
Liu
Jun
J
Zhang
Baohong
B
Cox
Stephen B
SB
Cobb
George P
GP
D004305:Dose-Response Relationship, Drug; D053834:Explosive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016368:Frameshift Mutation / Q000235:genetics; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000494:pharmacology; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000235:genetics*; D014227:Triazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D053834:Explosive Agents; D009153:Mutagens; D009603:Nitroso Compounds; D014227:Triazines; C009160:cyclonite