Reproductive toxicity of bimolane in mice and rabbits

Bimolane (AT-1727), 1,2-bis (4-morpholinomethyl-3,5-dioxopiperazinyl)-ethane, is a new antitumor drug, synthesized first in our institute. When the mice were injected ip bimolane 3.7 or 37.2 mg/kg on d 6-15 after mated, 23 or 100% of the embryos were resorbed, while the surviving fetuses remained normal. After ip bimolane 7.4 or 14.9 mg/kg, the weights of living fetuses were all less than that of the control group (P less than 0.01). After ig bimolane 140 mg/kg to the mice on d 6-15 after mated, 43% of the fetuses developed subcutaneous edema, but no other abnormalities were seen. When the rabbits were given ip bimolane 30 mg/kg on d 7-18 after mated, all the embryos were resorbed. On d 10 after mated ip a single dose of bimolane 74.4 mg/kg to the mice caused nanomelia (34%) and subcutaneous hematoma (55%). Therefore, teratogenicity of bimolane was observed in mice.