Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part I. Beagle Dogs

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.