Acute toxicity of 2-thiotriazone in rats

The acute toxicity of 2-thiotriazone (TTZ) was evaluated in adult and immature rats of both sexes. 2-Thiotriazone produced marked pulmonary toxicity in rats that was both age and sex dependent. TTZ was highly toxic to adult male rats when given as a single dose (oral LD50 = 4.6 mg/kg and ip LD50 = 1.4 mg/kg) with 100% mortality being observed at 10 mg/kg orally and 5 mg/kg intraperitoneally (ip). Female rats were more resistant than males with only 40% mortality at concentrations of 10-100 mg/kg orally. Immature rats (30-40 days of age) of both sexes showed no response when TTZ was administered at concentrations of 10-1000 mg/kg either orally or ip. Gross and histological examination of lung tissue from rats affected by TTZ revealed severe pulmonary edema, effusion, and mottling of the lungs. Significant increases in lung weights were also observed. Studies with diethylmaleate (DEM) and TTZ indicated that DEM pretreatment potentiated the toxic effects of TTZ in adult male, adult female, and immature rats. Lung weights in DEM/TTZ-treated rats were twice that of animals treated with TTZ alone. The results of the present study indicate that TTZ is highly toxic to male rats with the lungs being particularly vulnerable to its effects and that TTZ toxicity is enhanced by DEM pretreatment.