[Chronic toxicity of aclacinomycin A in rats (author's transl)]

Male and female Wistar rats were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at 5 dosage levels (0.08, 0.15, 0.3, 0.6 and 1.2 mg/kg/day) by daily intraperitoneal injections for 180 days for a chronic toxicity study. Recovery was also examined for 30 days after completion of the administration. Mortality was as follows: Male 5/24, female 3/24 in 0.6 mg/kg/day dose group and male 19/24, female 8/24 in 1.2 mg/kg/day dose group. Anorexia, depression of spontaneous activity and unformed feces were observed in rats in 0.6 and 1.2 mg/kg/day dose groups after day 90. Body weight gain decreased during the period. No significant change was found in rats receiving the drug at 0.3 and less mg/kg/day all through the observation period. Remarkable decreases in WBC count were noted in rats in the two highest dose groups on day 90. Autopsy findings included atrophy of the thymus and hyperemia and hemorrhage in the gastrointestinal tract and mesenteric lymph node in the animals treated at 0.6 and 1.2 mg/kg/day in the examination on day 90. Histologically, atrophy of the thymus and hyperplasia of the spleen were observed in the higher dose groups on day 90. But no remarkable abnormalities were found in histological examination on day 180. The changes in general symptom and decrease in body weight gain, which were observed during the dosing period in rats in 0.6 mg/kg/day dose group, recovered within 30 days after the drug administration was discontinued but no complete recovery of the WBC count decrease was observed.