© 1986 Oxford University Press
research-article |
Teratology Study in Rats with Amsacrine, an Antineoplastic Agent1
Department of Pathology and Experimental Toxicology, Warner-Lamberl/Parke-Davis, Pharmaceutical Research 2800 Plymouth Road, Ann Arbor, Michigan 48105
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 used in the treatment of refractory leukemias, was evaluated for its teratogenic potential in pregnant rats. The compound was given by intrapentoneal (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.