title: Teratology study in rats with amsacrine, an antineoplastic agent.
abstract: Amsacrine, an acridinylamino derivative used in the treatment of refractory leukemias, was evaluated for its teratogenic potential in pregnant rats. The compound was given by intraperitoneal (ip) administration on Days 6 to 9 of gestation to groups of 20 female CD rats at levels of 0.5, 1.0, and 2.0 mg/kg. Appropriate vehicle and untreated controls were included. Dams given 2.0 mg/kg lost weight during and after the treatment period. Food consumption was comparable to controls at all dose levels except for the high dose group in the post-treatment period. Decreased litter size, increased postimplantation loss, and reduced fetal weights occurred with doses of 2.0 mg/kg. Significantly reduced fetal body weight and increased incidence of stunting were the only adverse findings at 0.5 and 1.0 mg/kg, respectively. Two fetuses at 2.0 mg/kg, one at 1.0 mg/kg, one at 0.5 mg/kg, and two vehicle control fetuses had gross abnormalities. Fetotoxicity, manifested by inhibition of osteogenesis and minor skeletal abnormalities, occurred with doses of 0.5 mg/kg or more. The results indicate that amsacrine was embryolethal to rats at doses of 2.0 mg/kg and embryotoxic at lower dose levels. Teratogenicity was not evident at doses which did not affect fetal survival.
mesh_terms: D000014:Abnormalities, Drug-Induced; D000677:Amsacrine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005865:Gestational Age; D011247:Pregnancy; D051381:Rats; D013723:Teratogens
chemical_list: D013723:Teratogens; D000677:Amsacrine