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 LD50 for .alpha.-TNT in corn oil was 1320 and 794 mg/kg in male and female rats, respectively, and 660 mg/kg in 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. All species receiving the highest doses exhibited anemia with reduced erythrocytes, Hb 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 glutamic pyruvic transaminase [SGPT] activity in dogs and rats; no effect on serum glutamicoxaloacetic transaminase activty 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 effect 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 as follows: dogs, 0.20; rats, 1.42; and mice, 7.76 mg/kg.cntdot.day.