title: Cytotoxic and genotoxic effects of energetic compounds on bacterial and mammalian cells in vitro.
abstract: The mutagenicity and toxicity of energetic compounds such as 2,4, 6-trinitrotoluene (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. Mutagenicity was evaluated with the Salmonella fluctuation test (FT) and the V79 Chinese hamster lung cell mutagenicity assay. Cytotoxicity was evaluated using 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 were without effect at their maximal aqueous solubility limits. The primary TNT 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 TA98 strain, addition of rat liver S9 resulted in either no effect, or decreased activity. None of the tested compounds were mutagenic for the V79 mammalian cells with or without S9 metabolic activation. Thus, the FT assay was more sensitive to the genotoxic effects of energetic compounds than was the 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 that genotoxicity could actually exist in other mammalian cells. In view of earlier reports and this study, mutagenicity testing of environmental samples should be considered as part of the hazard assessment of sites contaminated by TNT and related products.
authors.affiliation: Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada. bernard.lachance@nrc.ca
authors.forename: B
authors.initials: B
authors.lastname: Lachance
authors.forename: P Y
authors.initials: PY
authors.lastname: Robidoux
authors.forename: J
authors.initials: J
authors.lastname: Hawari
authors.forename: G
authors.initials: G
authors.lastname: Ampleman
authors.forename: S
authors.initials: S
authors.lastname: Thiboutot
authors.forename: G I
authors.initials: GI
authors.lastname: Sunahara
mesh_terms: D000818:Animals; D001392:Azocines / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004785:Environmental Pollutants / Q000633:toxicity*; D006573:Heterocyclic Compounds, 1-Ring / Q000633:toxicity; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014050:Toluene / Q000031:analogs & derivatives / Q000633:toxicity; D014227:Triazines / Q000633:toxicity; D014301:Trinitrobenzenes / Q000633:toxicity; D014303:Trinitrotoluene / Q000633:toxicity*
chemical_list: D001392:Azocines; D004785:Environmental Pollutants; D006573:Heterocyclic Compounds, 1-Ring; D009153:Mutagens; D014227:Triazines; D014301:Trinitrobenzenes; D014303:Trinitrotoluene; C029222:sym-trinitrobenzene; D014050:Toluene; D007041:Hypoxanthine Phosphoribosyltransferase; C007950:octogen; C009160:cyclonite