Teratogenic and cytogenetic effects of hycanthone in mice and rabbits

Hycanthone administered daily to pregnant mice at 3 dose levels on days 61–11 of gestation produced embryolethality and a depression of fetal body weights. At 12.5 mg/kg, no teratogenic effects were observed; at 25 mg/kg, fetal malforrnations occurred, and at 50 mg/kg, more than 90% of the conceptuses were killed. When hycanthone was administered to mice as single injections on days 5–9 of gestation embryolethal and teratogenic effects appeared to be limited to days 6 and 7. In rabbits hycanthone treatment on days 7, 8, and 9 of gestation produced embryolethality at a dose of 25 mg/kg and both embryolethality and teratogenicity at 50 mg/kg. Although hycanthone depressed the mitotic Index and induced chromosomal aberrations in microcultures of blood from untreated rabbits no cytogenetic effects of the drug were observed in either adult or fetal mice and rabbits in vivo.