SINGLE ADMINISTRATION TOXICITY STUDIES OF T-3761 IN MICE, RATS AND DOGS

Single dose toxicity studies of T-3761 were carried out in mice, rats and dogs, and the following results were obtained. 1. The approximate lethal dose of T-3761 were more than 5,000mg/kg for mice and rats, more than 2,000 mg/kg for dogs with oral administration, and more than 5,000 mg/kg for mice and rats with subcutaneous injection. LD50 values with intravenous injection were 783 mg/kg for male mice, 832 mg/kg for female mice, 341 mg/kg for male rats, and 403 mg/kg for female rats. Two dogs given 200 mg/kg did not die but one of the two treated with 400 mg/kg died after intravenous injection. The approximate lethal dose for dog was 400 mg/kg. 2. Neither abnormal symptoms and macroscopic findings nor deaths were observed in mice and rats treated orally. Granuloma around precipitates of T-3761 at the injection site was seen in mice and rats injected subcutaneously. Slight increase of white blood cell count, serum GOT, CPK and urea nitrogen were transiently found in dogs treated orally. Neither abnormal macroscopic findings nor deaths were observed in dogs treated orally. 3. Decreased motor activity and irregular breathing were observed in mice and rats injected intravenously. In dying animals, tonic or clonic convulsions were observed. Vomiting, hyperemia of ophthalmic mucosa, edema of face, decrease of motor activity, salivation and decrease in body temperature were observed in dogs injected intravenously. At higher doses, scream and tachypnea were observed while injecting. Hematological examinations disclosed that increases in red blood cell count, white blood cell count, hematocrit and hemoglobin were found transiently. In biochemical examinations, increases in serum GOT, GPT, urea nitrogen and creatinine were found transiently. One dog intravenously injected 400 mg/kg, showed tonic convulsion and died.