The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for 2,4,6-TRINITROTOLUENE

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

Prepared by: Dennis M. Opresko, Ph.D., Chemical Hazard Evaluation Group in the Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, Oak Ridge National Laboratory*.

Prepared for: Oak Ridge Reservation Environmental Restoration Program.

*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

2,4,6-Trinitrotoluene (TNT) is used as a high explosive in military armaments and as a chemical intermediate in the manufacture of dyestuffs and photographic chemicals (Sax and Lewis 1987). TNT is likely to enter the environment in wastewater effluents from production facilities and from leachates at waste disposal sites. Mobility in soil may be limited by strong adsorption to soil particles (EPA 1990).

TNT is absorbed through the gastrointestinal tract, skin, and lungs; is distributed primarily to the liver, kidneys, lungs, and fat; and is excreted mainly in the urine and bile (El-hawari et al. 1981). Metabolism occurs by nitroreduction to amino and hydroxylamino derivatives and by oxidation to benzyl alcohol and benzoic acid derivatives (El-hawari et al. 1981).

In animals, signs of acute toxicity to TNT include ataxia, tremors, and mild convulsions. Splenic hemosiderosis, leukopenia, thrombocytosis, slight hepatomegaly, and increase in kidney weight occurred in mice fed a dietary level equivalent to 700 mg TNT/kg/day for 28 days (Levine et al. 1984b). Oral LD50 values of 660 to 1320 mg/kg have been reported for rats (Dilley et al. 1982).

The primary target organs for TNT toxicity in experimental animals following subchronic and chronic oral exposures are (1) liver (hepatocytomegaly and cirrhosis), (2) blood (hemolytic anemia with secondary alterations in the spleen), and (3) testes (degeneration of the germinal epithelium lining the seminiferous tubules). The LOAEL for hepatotoxicity in dogs was 0.5 mg/kg/day (Levine et al. 1990a).

Chronic oral toxicity studies on rats have also demonstrated TNT-induced anemia and hepatotoxicity, as well as adverse effects on the kidney (hypertrophy and nephropathy) and sternal bone marrow fibrosis (Furedi et al. 1984a).

The reference dose (RfD) for chronic oral exposures, 0.0005 mg/kg/day, is based on a LOAEL of 0.5 mg/kg/day for liver effects in dogs (EPA 1991b). The subchronic oral RfD is the same as the chronic RfD and is based on the same study (EPA 1991a).

Information on the inhalation toxicity of TNT is derived mainly from occupational exposure studies, which indicate that the major effects of chronic exposure to TNT are anemia (decreases in Hgb, Hct, and RBC count), liver dysfunction (increases in serum lactic dehydrogenase, glutamic oxaloacetic transaminase, and bilirubin), and cataracts (equatorial lens opacities) (EPA 1989, 1990). Other reported effects of TNT exposure include dermatitis, leukocytosis, neurological disorders, and nephrotoxicity (Cone 1944, Zakhari and Villaume 1978).

An inhalation reference concentration (RfC) for TNT has not been derived.

Limited information is available on the reproductive or developmental toxicity of TNT to animals or humans following inhalation exposures. Information from occupational exposure studies suggests that TNT may cause menstrual disorders and male impotency (Zakhari and Villaume 1978, Jiang et al. 1991).

No epidemiological evidence is available showing an association between chronic TNT exposure and tumorigenicity in humans. In animal carcinogenicity studies, a significant increase in urinary bladder papillomas and carcinomas was seen in female F344 rats dosed with 50 mg TNT/kg/day for 24 mo (Furedi et al. 1984a). This study was used by EPA to calculate a slope factor of 0.03 (mg/kg/day)-1 (EPA 1991). TNT is classified in weight-of-evidence Group C, possible human carcinogen (EPA 1991a, b).

Retrieve Toxicity Profiles Formal Version

Last Updated 2/13/98

Join the RAIS User's Group for Updates