Mammalian Toxicity of Munitions Compounds. Phase II. Effects of Multiple Doses Part II. 2,4-Dinitrotoluene.

摘要

The effects of 2,4-DNT after oral administration for up to 13 weeks were investigated in dogs, rats, and mice. A detailed study of the disposition and metabolism was performed in rats and the metabolic pathways compared in dogs, rats, mice, rabbits, and monkeys. The main target organs for the toxic effects of 2,4-DNT were the erythrocytes (methemoglobinemia leading to Heinz bodies and to anemia and its sequelae), the testes (depressed spermatogenesis), and the neuromuscular system (a rigid paralysis associated with mild central nervous system lesions). The highest no effect levels were 5 mg/kg/day in male and female dogs, less than 34 mg/kg/day in male rats and less than 38 mg/kg/day in female rats, and 137 mg/kg/day in male mice and 147 mg/kg/day in female mice. 14C-2,4-DNT was well absorbed after oral dosing by all species tested except mice. The radiolabel was concentrated in the liver and kideny. Primary biotransformation reactions were reduction of one or both nitros to amines and oxidation of the methyl to a benzyl alcohol or benzoic acid. Secondary conjugation reactions occurred before excretion in the urine. (Author)