Determination of the Chronic Mammalian Toxicological Effects of TNT (Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the Fischer 344 Rat). Volume 1

摘要

This study was conducted to evaluate the toxicity of the munitions compound 2,4,6-trinitro-toluene (TNT) in Fischer 344 rats when administered in their diet for up to 24 months. Groups of 75 rats per sex received TNT at doses of 0, 0.4, 2, 10 and 50 mg/kg/day. Ten rats/sex/dose were sacrificed following 6 and 12 months on test with surviving animals sacrificed after 24 months of treatment. Toxicologic endpoints included clinical signs, body weights, food consumption, hematology, clinical chemistry, opthalmology, organ weights, and gross and tissue morphology. The major toxic effects observed during the administration of TNT to F344 rats for up to 24 months included anemia with secondary splenic lesions, hepatotoxicity, and urogenital lesions. In addition, hyperplastic/neoplastic lesions of the liver, kidneys and urinary bladder were observed. Based on the observance of splenic congestion, increased amounts of pigment deposition in the kidneys and bone marrow fibrosis at doses of 2.0 mg/kg/day or greater, the no-effect level under the conditions of the present study is 0.4 mg/kg/day. Keywords: Methemoglobinemia.