Short‐term oral toxicity of 2,4,6‐trinitrotoluene in mice, rats, and dogs

Abstract

The short-term oral toxicity of 2,4,6-trinitrotoluene (alpha-TNT) was determined in dogs, rats, and mice. Single-dose oral LD50s for alpha-TNT in corn oil were 1320 and 794 mg/kg in male and female rats, respectively, and 660 mg/kg in both male and female mice. For multiple-dose studies, dogs were dosed daily for up to 13 wk with alpha-TNT at 0, 0.2, 2.0, or 20 mg/kg by capsule; rats received 0, 0.002, 0.01, 0.05, or 0.25% and mice received 0, 0.001, 0.005, 0.025, or 0.125% alpha-TNT in their diets over the same period. All species receiving the highest doses exhibited anemia, with reduced erythrocytes, hemoglobin, and hematocrit. Alterations were observed in organ weights, including enlarged spleens (accompanied by hemosiderosis) and livers, and depressed body weight and/or body weight gain (temporary in dogs and mice). Alterations in clinical chemistry values included elevated cholesterol and depressed serum glutamicpyruvic transaminase activity in dogs and rats; no effect on serum glutamic-oxaloacetic transaminase activity was observed. Some effects, such as SGPT depression in rats, appeared after 13 wk, suggesting a cumulative toxicity. Reduced testes size was observed in rats at the highest dose regardless of length of exposure. Most of the toxic effects were reversible, but testicular atrophy was not in rats allowed a 4-wk recovery period after treatment. Signs of anemia were present at intermediate dose levels. "No observable effects" levels for alpha-TNT were: dogs, 0.20; rats, 1.42; and mice, 7.76 mg/kg . d.

Nitroaromatic Munition Compounds: Environmental Effects and Screening Values

“…The calculated log Kow value of 2.03 (Liu et al 1983a (Opresko 1995a). In the first study, Dilley et al (1982) administered TNT to dogs, rats, and mice for 13 wk. Groups of 2 male and 2 female beagle dogs were administered doses of 0, 0.2, 2.0, or 20 mglkg/d in gelatin capsules.…”

Soils contaminated with explosives: Environmental fate and evaluation of state-of-the-art remediation processes (IUPAC Technical Report)

“…Studies on mice, rats, and dogs have demonstrated that TNT exposure may result in a variety of adverse health effects including cardiovascular, gastrointestinal, hematological, hepatic, renal, immunological, neurological, reproductive, developmental, genotoxic, and carcinogenetic effects [186]. Recent mammalian studies conducted on mice and rats [222,223] administered up to 601 mg TNT per kg body weight to whitefooted mice over a 14-day period. While fatalities were not observed [222], several indicators of nonspecific immunity, including increased spleen weight, were related to dose.…”

“…Recent mammalian studies conducted on mice and rats [222,223] administered up to 601 mg TNT per kg body weight to whitefooted mice over a 14-day period. While fatalities were not observed [222], several indicators of nonspecific immunity, including increased spleen weight, were related to dose. Results of dosing studies with hispid cotton rats suggest that hepatic enzymes and hemolytic anemia may be useful biomarkers of terrestrial contamination by explosives [223].…”

Effects of 2,4,6-Trinitrotoluene in a Holistic Environmental Exposure Regime on a Terrestrial Salamander, Ambystoma tigrinum

“…The presence of these compounds in the sediments and soils from munitions facilities has been demonstrated at concentrations high enough to adversely affect some algal, vascular plant, invertebrate, and fish species (6,28). Toxic effects of 2,4,6-trinitrotoluene (TNT) exposure on mammals have been investigated (9,21,22); however, information specific to amphibian exposures is lacking. Yet, TNT and metabolites have been shown to bioaccumulate in terrestrial salamanders in a soil matrix (19).…”