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Genotoxic activity of nitroaromatic explosives and related compounds in Salmonella typhimurium
Abstract:
A number of nitroaromatic explosives and related compounds were examined for mutagenic activity with the Salmonella/mammalian microsome test. 9 of 11 nitroaromatics tested were mutagenic, including 2,4,6-trinitrotoluene, the most widely produced military explosive. All the nitroaromatics, except 2,4,6-trinitrophenol and 2,3,5-trinitroresorcinol, were at least an order of magnitude more mutagenic than 3 dinitrotoluene (DNT) isomers. The most active compound was 2,3,5-trinitronaphthalene, which was approximately 5000 times more mutagenic than DNT isomers. These compounds induced predominantly frameshift mutations. The mutagenic activity did not require S9 activation, but was largely dependent on the presence of an intact nitroreductase capability in the test bacteria. This implied that reduced metabolites, possibly hydroxylamines, are the proximal mutagenic intermediates.
Insights
Many nitroaromatic explosives, including 2,4,6-trinitrotoluene, show mutagenic activity in bacterial tests. Their mutagenicity is linked to nitroreductase activity, suggesting reduced metabolites are key mutagens.
Area of Science:
- Environmental Science
- Toxicology
- Chemical Mutagenesis
Background:
- Nitroaromatic compounds are widely used, particularly as military explosives.
- Assessing the mutagenic potential of these compounds is crucial for environmental and health risk evaluation.
- Previous studies have indicated potential genotoxicity of some nitroaromatics.
Purpose of the Study:
- To evaluate the mutagenic activity of various nitroaromatic explosives and related compounds.
- To identify specific nitroaromatics with significant mutagenic potential.
- To elucidate the mechanism underlying the mutagenic activity of these compounds.
Main Methods:
- Utilized the Salmonella/mammalian microsome assay (Ames test) to assess mutagenicity.
- Tested eleven different nitroaromatic compounds, including 2,4,6-trinitrotoluene.
- Investigated the role of bacterial nitroreductase activity and S9 activation in mutagenicity.
Main Results:
- Nine out of eleven tested nitroaromatics exhibited mutagenic activity.
- 2,3,5-trinitronaphthalene was the most potent mutagen, approximately 5000 times more mutagenic than dinitrotoluene (DNT) isomers.
- Mutagenic activity was primarily frameshift mutations and was dependent on bacterial nitroreductase, not S9 activation.
Conclusions:
- Nitroaromatic explosives, notably 2,4,6-trinitrotoluene, pose a mutagenic risk.
- The mutagenic mechanism involves nitroreduction, producing potentially hazardous hydroxylamine intermediates.
- Further research into the environmental fate and toxicological impact of these compounds is warranted.