[Acute toxicological studies of captopril in rats and mice]

The acute toxicity of captopril, a potential inhibitor of angiotensin converting enzyme, was studied in Sprague-Dawley rats and ICR mice. In the oral administration, a decrease of spontaneous motor activity, lacrimation, salivation and decline of body temperature was noted in the rats and mice. In the mice, tarry stool was also noted. The LD50 was estimated as: 4249 mg/kg in male mice, 5050 mg/kg in female mice, 4336 mg/kg in male rats and 4245 mg/kg in female rats, In the dead animals, a hemorrhagic erosion or ulcer was recognized in the glandular stomach. An intravenous captopril in mice, caused immediate death by dyspnea in some animals within 3 minutes, but delayed death was also occurred within 24 hours showing a decrease of spontaneous motor activity and decline of body temperature. The LD50 was estimated as 3154 mg/kg in male mice and 3225 mg/kg in female mice. A single intravenous administration of captopril in dose of 1600 mg/kg did not cause any death in the rats of both sexes. The mice of both sexes well tolerated a single subcutaneous administration of captopril in a dose of 2400 mg/kg. No death occurred in rats of both sexes received subcutaneously captopril in a dose of 1200 mg/kg. At an injection site, a necrotic ulcer was noted in the skin of rats and mice which received subcutaneously captopril in a dose of 1600 mg/kg or more and 1200 mg/kg, respectively.