Subchronic and chronic toxicities of 2,4-dinitrotoluene were studied in CD® rats. Feeding of 2,4-dinitrotoluene for 13 weeks at a low dose of 34 mg/kg per day in males and 38 mg/kg per day in females caused depressed weight gain. The middle dose of 93 and 108 mg/kg per day, respectively, was toxic, caused reticulocytosis and splenic hemosiderosis, and decreased spermatogenesis. The high dose of 266 and 145 mg/kg per day, respectively, was more toxic and lethal. Some rats had widespread and stiff-legged gaits and demyelination in the cerebellum and brain stem. After feeding up to 2 years, the low dose (0.57 and 0.71 mg/kg per day, respectively) caused no apparent toxic effects. The middle dose (3.9 and 5.1 mg/kg per day, respectively) was toxic; the high dose (34 and 45 mg/kg per day) was more toxic and shortened the life span. Target organs included the blood (toxic anemia), the liver (hepatocellular carcinoma), the testis (atrophy and depression of spermatogenesis), the connective tissue in males (fibromas), the mammary tissue in females (fibroadenomas), and the neuromuscular system in some rats.
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