Chronic toxicity studies on 1,3,5-trinitrobenzene in Fischer 344 rats. Final report, 1 May 1993-30 April 1995
Chronic toxic effects of I ,3,5-tnnitriotrobenzene (TNB) in male and female Fischer rats were evaluated by feeding certified powdered laboratory chow diet supplemented with varied concentrations of TNB (0, 5, 60 and 300 mg/kg diet). The study was designed to accommodate three interim sacrifices (10 rats/group/sex) at 90, 180 and 365 days. The final sacrifice was performed after two years. All data related to these interim sacrifices are presented independently in appendices J to L. The calculated average TNB consumption for females was 0.23, 2.68 and 13.31 mg/kg/day and was 0.22, 2.64 and 13.44 mg/kg/day for males. Terminal body weights were significantly decreased in both sexes in the 300 mg/kg group. Relative spleen weights were decreased in both sexes in the 300 mg/kg group while brain weights were increased in females in this same group. Methemoglobin was increased in both sexes in the 300 mg/kg group while other hematological effects noted at the interim sacrifice times were not evident at two years. Histopathological examinations suggested treatment related changes in both sexes involving the kidneys (cytoplasmic/hyaline droplets) in the 60 and 300 mg/kg groups and the spleen (erythroid cell hyperplasia and pigment deposition) in the 300 mg/kg group. The cytoplasmic/hyaline droplets were characterized by immunohistochemistry as alpha-2u-globulin. These renal droplets were also noted at the interim sacrifice times. A no observed adverse effect level (NOAEL) was established in this study at 2.68 mg/kg b.w./day for F-344 rats administered TNB for two years.
- Research Organization:
- Environmental Protection Agency, Cincinnati, OH (United States). Risk Reduction Engineering Lab.
- OSTI ID:
- 420183
- Report Number(s):
- AD-A--315216/2/XAB; CNN: Contract MIPR-93MM3558
- Country of Publication:
- United States
- Language:
- English
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