chapter  9
16 Pages

Mechanisms of the Mammalian Cell Cytotoxicity of Explosives

Explosives and their degradation products can be toxic and mutagenic to humans, and other mammalian species (see Chapters 7, 8, and 10). The toxic effects of 2,4,6-trinitrotoluene (TNT) were observed as early as the 1920s [1]. Oral administration of TNT, picric acid, and 2,4,6-trinitrophenyl-N-methylnitramine (tetryl) to rats and mice was accompanied by hemolytic anemia, methemoglobinemia (increased formation of the ferric state of hemoglobin unable to bind oxygen), reduced hematocrit (erythrocyte concentration in blood, v/v), liver damage, splenomegaly, hypercholesterolemia, and testicular atrophy [2-6]. The data on the mutagenic activity of TNT and its metabolites in mammalian cells were equivocal, depending on the cell line and conditions [7-10]. The exposure of humans to nitroaromatic explosives is accompanied by multiple toxic effects, which are inuenced by the genetic or individual susceptibility, and by the workplace standards [1,11,12]. Increased exposure to TNT causes methemoglobinemia [11]; cataracts [12-14]; reproductive toxicity [15]; skin lesions and dermatitis [16]; and urinary tract, kidney, and liver tumors

9.1 Introduction .................................................................................................. 211 9.2 Enzymatic Reactions of Nitroaromatic Explosives ...................................... 213

9.2.1 Free Radical Reactions of Nitroaromatic Explosives ....................... 213 9.2.2 Formation of Stable Metabolites of Nitroaromatic Explosives ........ 218

9.3 Mammalian Cell Cytotoxicity of Nitroaromatic Explosives ........................ 221 9.4 Mammalian Cell Cytotoxiciy and Enzymatic Reactions of Other

Explosives ..................................................................................................... 222 9.5 Concluding Remarks .................................................................................... 223 References .............................................................................................................. 223

[17,18]. An increased incidence of acute and chronic leukemia has also been reported following chronic exposure [19].