Teratology Study in Rats with Amsacrine, an Antineoplastic Agent

Teratology Study in Rats with Amsacrine, an Antineoplastic Agent.ANDERSON, J. A., PETRERE, J. A., SAKOWSKI, R., FITZGERALD, J.E., AND DE LA IGLESIA, F. A. (1986). Fundam. Appl. Toxicol.7, 214–220. Amsacrine, an acndinylamino derivative usedin the treatment of refractory leukemias, was evaluated forits teratogenic potential in pregnant rats. The compound wasgiven by intrapentoneal (ip) administration on Days 6 to 9 ofgestation to groups of 20 female CD rats at levels of 0.5, 1.0,and 2.0 mg/kg. Appropriate vehicle and untreated controls wereincluded. Dams given 2.0 mg/kg lost weight during and afterthe treatment period. Food consumption was comparable to controlsat all dose levels except for the high dose group in the post-treatmentperiod. 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 incidenceof 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, oneat 0.5 mg/kg, and two vehicle control fetuses had gross abnormalities.Fetotoxicity, manifested by inhibition of osteogenesis and minorskeletal abnormalities, occurred with doses of 0.5 mg/kg ormore. The results indicate that amsacrine was embryolethal torats at doses of 2.0 mg/kg and embryotoxic at lower dose levels.Teratogenicity was not evident at doses which did not affectfetal survival.