No abstract

Subchronic and chronic toxicities of 2,4-dinitrotoluene (2,4-DNT) were evaluated in CD-1® mice. 2,4-DNT was more toxic to males than to females. Male mice fed 47 mg/kg per day or 137 mg/kg per day for 13 weeks gained less weight. However, females fed 52 or 147 mg/kg per day had no adverse effects. Feeding of 413 mg/kg per day for males or 468 mg/kg per day for females lowered feed consumption, depressed body weight, and caused mild anemia and mild hepatocellular dysplasia in both sexes and mild testicular degeneration in males. Both males and females were fed an average of 14 (low dose), 95 (middle dose), or 898 mg/kg per day (high dose) for up to 24 months. In males, there was a high incidence of epithelial renal tumor and hepatocellular dysplasia in all dose groups, Incidence of testicular atrophy was increased in the middle-and high-dose males. In addition, the high dose caused toxic anemia and death. In females, the high dose was associated with toxic anemia, hepatocellular dysplasia, nonfunctional follicle with a lack of corpora lutea, an effect analogous to the testiclar atrophy in males, and death. A generalized pigmentation, probably of 2,4-DNT metabolite origin, was seen in many tissues of especially the high-dose males and females.

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.

No abstract

Subchronic and chronic toxicities of 2,4-dinitrotoluene (2,4-DNT) were studied in beagle dogs. The major adverse effect of 2,4-DNT in dogs was a neuropathy, characterized by incoordination and paralysis. There were vacuolation, endothelial proliferation, and gliosis of the cerebellums of some affected dogs. These effects were seen in 1 dog given 1.5 mg/kg per day for 2 years, in all dogs given 10 mg/kg per day within 6 months, and in all dogs given 25 mg/kg per day within 2 months. There was great variation between individuals in onset and severity of adverse effects. Some dogs progressed to a complete paralysis, leading to death. Methemoglobin and its sequelae were common, but not life threatening. Heinz bodies were a useful indicator of this effect. Less important adverse effects seen included testicular degeneration and biliary tract hyperplasia. No changes were found in tumor incidence, immunoglobin E and cytogenetic assays, and other routine hematologic and clinical laboratory tests.