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

  • 정문구 (한국화학연구소 안전성연구부) ;
  • 한상섭 (한국화학연구소 안전성연구부) ;
  • 양중익 (동아제약 주식회사 중앙 연구소) ;
  • 노정구 (한국화학연구소 안전성연구부)
  • Published : 1994.04.01

Abstract

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.

Keywords