Chronic and Carcinogenic Study of Trinitroglycerin in Rats, Mice and Dogs

Abstract

Four groups of 38 male and 38 female Charles River CD albino rats and of CD-1 mice were fed diets containing 0 (control), 0.01, 0.1, or 1.0% trinitroglycerin (TNG) for 2 years. Rats fed the high dose had decreased food consumption and weight gain. Periodic hematological examination found compensated anemia with reticulocytosis, elevated serum transaminases and occasional methemoglobinemia in high dosage rats. At the 1 year necropsy, 8 high-dose rats examined had cholangiofibrosis and some had hyperplastic foci in the liver. At 2 years, all 13 surviving high-dose rats and 6 of the 16 middle-dose rats had enlarged and grossly abnormal livers which on microscopic examination revealed severe cholangiofibrosis and hepatocellular carcinomas. One-half of the high-dose males had interstitial cell tumors in the testes. No apparent toxic effects were observed in the low-dose animals. Mice fed the high-dose of TNG had decreased food consumption and weight gain. At 1 year, the high-dose mice had heme-derived pigment deposits in various organs, and liver dysplasia. At 2 years, the pigmentation occurred in most high-dose and some middle-dose mice while minimal liver dysplasia was found in all the treated groups. Four groups of 6 male and 6 female beagle dogs were given capsules containing 0 (control), 1, 5 or 25 mg/kg/day of TNG for 1 year. Transient methemoglobinemia only was observed in most of the dogs at all the dose levels.

This research was supported by US Army Medical Research and Development Command under Contract No. DAMD 17-74-C-4073