Toxic interactions of the munitions compounds TNT and RDX in F344 rats.

The potential toxic interactions in F344 rats of the munitions compounds trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) were examined following their coadministration in the diet. Groups of 10 rats per sex received TNT at doses of 5 or 125 mg/kg/day, RDX at doses of 30, 100, or 300 mg/kg/day, and combinations thereof for 13 weeks. Thirty rats per sex served as controls. Toxicologic endpoints included clinical observations, body weight, food consumption, hematology, clinical chemistry, organ weights, and tissue morphology. The major toxic effects following dietary administration of TNT to rats included anemia, hypercholesterolemia, and hepatomegaly, splenomegaly, and testicular atrophy with their accompanying histologic lesions. RDX intoxication in rats included hypotriglyceridemia, behavioral changes, and mortality. Most of the toxic effects of these chemicals were partially antagonized following their coadministration.

Six month oral toxicity study of trinitrotoluene in beagle dogs.

This study was conducted to evaluate the toxicity of the munitions compound 2,4,6-trinitrotoluene (TNT; CAS Reg. No. 118-96-7) in beagle dogs when administered daily for 26 weeks by capsule. Groups of six dogs per sex received TNT at doses of 0 (vehicle controls), 0.5, 2, 8, or 32 mg/kg/day. Toxicologic endpoints included clinical signs, body weights, food consumption, clinical biochemistry, hematology, urinalyses, organ weights, and gross and tissue morphology. The major toxic effects following the oral administration of TNT to dogs included hemolytic anemia, methemoglobinemia, liver injury, splenomegaly with accompanying histologic lesions, and death. Only the highest dose given proved to be lethal. Hepatocytic cloudy swelling and hepatocytomegaly were apparent at all doses tested. Thus, a no observable effect level was not established in this investigation.

Subchronic toxicity of trinitrotoluene in Fischer 344 rats.

This study was conducted to evaluate the toxicity of trinitrotoluene (TNT) in Fischer 344 rats when administered in the diet for 13 weeks. Groups of 10 rats per sex received TNT at doses of 1, 5, 25, 125 or 300 mg/kg/day. Thirty rats per sex served as untreated controls. Toxicologic endpoints included clinical signs, body weight, food consumption, hematology, clinical biochemistry, organ weights and gross/histopathology. Toxic effects following 125 mg/kg/day or greater included decreased food intake and body weight gains, elevated serum cholesterol levels, and anemia (reduced hemoglobin, hematocrit and RBC counts). Splenomegaly, hepatomegaly/hepatocytomegaly and testicular atrophy with degeneration of the seminiferous tubular epithelium were also seen at 125 and 300 mg/kg/day. Hemosiderin-laden macrophages, congestion of the splenic red pulp, methemoglobin production indicative of the oxidizing activity of TNT and/or its metabolites, and the lack of bone marrow toxicity suggested hemolysis as the mechanism of anemia.

An assessment of RBE of Californium-252 for C57-Black/6 mouse fibrosarcoma by a precise afterloading technique.

Afterloading techniques were developed for the in vivo assessment of the RBE of californium-252 with respect of radium-226 using a fibrosarcoma in mice. The afterloading holder positions sources so that the tumor is uniformly irradiated. Using the end points of tumor volumetric studies up to 150 days after irradiation, it was found that the RBE ranged from 5-8 at clinically relevant dose rates and total doses.