Reproductive Toxicity Study of DA-125, A New Anthracycline Anticancer Agent: (I) Teratogenicity Study in Rats

새로운 안트라사이클린계 항암제 DA-125의 생식독성연구: (I) 랫트 최기형시험

DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.