Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 6. Volume 1

摘要

This study was conducted to evaluate the toxicity of the munitions compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX: CAS Reg. No. 121-82--4) in B6C3F1 mice when administered in their diet for up to 24 months. RDX purity was established to be 89.2-89.7% with the main containment of HMX. Groups of 85 mice per sex recieved RDX at doses of 0, 1.5, 7.0, 35.0 or 100.0 mg/kg/day. This last dose was reduced from 175 mg/kg/day in Test Week 11 due to high mortality. Ten mice/sex/dose were killed following 6 and 12 months on test with surviving animals killed after 24 months of treatment. Toxicologic endpoints included clinical signs, body weight, food consumption, hematology, clinical chemistry, ophthalmology, organweights, and gross and tissue morphology. The major toxic effects observed during the administration of RDX to B6C3F1 mice for up to 24 months included hepatotoxicity, possible CNS involvement, and testicular degeneration. In addition, hepatocellular adenomas and/or carcinomas were more prevalent for RDX-treated females that for corresponding controls. Whether serum cholesterol levels and/or the incidence of hepatocellular tumors were increased at the 7 mg/kg/day dose level is equivocal. The no-effect level under the conditions of the present study is 1.5 mg/kg/day. Keywords: RDX; Chronic toxicity; Hexahydro-1,3,5-trinitro-1,3,5-triazine; Hepatocarcinogen; Hybrid; Mouse; Hepatotoxicity; Carcinoma; Adenoma.