Thirteen Week Oral (Diet) Toxicity Study of Trinitrotoluene (TNT), Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) and TNT/RDX Mixtures in the Fischer 344 Rat

摘要

This study was conducted to evaluate the toxicity of the munitions compounds 2,4,6-trinitrotoluene (TNT; CAS Reg. No. 118-96-7) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX; CAS Reg. No. 121-82-4), and their potential toxic interactions in Fischer 344 rats when administered in the diet for at least 13 weeks. The data derived were also to be used to select dose levels for comprehensive chronic toxicity/carcinogenicity studies. Groups of 10 rats per sex received TNT at doses of 1, 5, 25, 125 or 300 mg/kg/day; RDX at doses of 10, 30, 100, 300 or 600 mg/kg/day; and the following combinations of these compounds: TNT 5/RDX 30 mg/kg/day, TNT 5/RDX 300 mg/kg/day, TNT 125/RDX 30 mg/kg/day, TNT 125 RDX 100 mg/kg/day, and TNT 125/RDX 300 mg/kg/day. Thirty rats per sex served as controls. Toxicologic endpoints included clinical signs, body weight, food consumption, hematology, clinical chemistry, organ weights, and gross and tissue morphology. An appropriate 10% reduction in body weight gain was seen for males receiving TNT 5 or 25 mg/kg/day, and for females administered TNT 125 mg/kg/day. Other toxic effects following the administration of TNT 25 mg/kg/day or greater included reduced food intake, hypercholesterolemia and anemia (reduced hemoglobin, hematocrit and erythrocyte counts). Splenomegaly with congestion and hemosiderosis of the red pulp, hepatomegaly with hepatocellular hypertrophy, testicular atrophy with degeneration of the seminiferous tubular epithelium and slight increases in kidney weights with deposition of pigment were also seen for rats receiving TNT 125 or 300 mg/kg/day. Elevated methemoglobin levels and cerebellar lesions were observed only at the TNT 300 mg/kg/day dose level.