Cytotoxic and genotoxic effects of energetic compounds on bacterial and mammalian cells in vitro

The mutagenicity and toxicity of energetic compounds such as 2,4,6-trinitro toluene (TNT), 1,3,5-trinitrobenzene (TNB), hexahydro-1,3,5-trinitro-1,3,5- triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and of amino/nitro derivatives of toluene were investigated in vitro. Mutag enicity was evaluated with the Salmonella fluctuation test (FT) and the V79 Chinese hamster lung cell mutagenicity assay. Cytotoxicity was evaluated u sing V79 and TK6 human lymphoblastic cells. For the TK6 and V79 assays, TNB and 2,4,6-triaminotoluene were more toxic than TNT, whereas RDX and HMX we re without effect at their maximal aqueous solubility limits. The primary T NT metabolites (2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2,4 -diamino-6-nitrotoluene and 2,6-diamino-4-nitrotoluene) were generally less cytotoxic than the parent compound. The FT results indicated that TNB, TNT and all the tested primary TNT metabolites were mutagenic. Except for the cases of 4-amino-2,6-dinitrotoluene and 2,4-diamino-6-nitrotoluene in the T A98 strain, addition of rat liver S9 resulted in either no effect, or decre ased activity. None of the tested compounds were mutagenic for the V79 mamm alian cells with or without S9 metabolic activation. Thus, the FT assay was more sensitive to the genotoxic effects of energetic compounds than was th e V79 test, suggesting that the FT might be a better screening tool for the presence of these explosives. The lack of mutagenicity of pure substances for V79 cells under the conditions used in this study does not preclude tha t genotoxicity could actually exist in other mammalian cells. In view of ea rlier reports and this study, mutagenicity testing of environmental samples should be considered as part of the hazard assessment of sites contaminate d by TNT and related products. (C) 1999 Elsevier Science B.V. All rights re served.