Hycanthone has been tested for embryotoxic activity in mice and rabbits. Treatment of mice on days 6–11 of gestation produced little embryotoxicity at a dose of 12.5 mg/kg, but produced teratogenic effects at 25 mg/kg and induced almost complete intrauterine death at 50 mg/kg. Single injections on various days of gestation demonstrated that the mouse conceptus is most sensitive to hycanthone‐induced teratogenesis on gestation days 6 and 7, at which time a high incidence of exencephaly and skeletal malformations was found. Hycanthone (50 mg/kg) given to pregnant mice on day 7 of gestation depressed DNA synthesis in embryonic tissue, an effect which was evident 30 minutes after drug treatment and which lasted at least 3 hours. Following a single injection of [3H‐U] hycanthone into 7‐day pregnant mice, radioactivity was rapidly cleared from the maternal plasma, having a half‐life of 1–2 hours; higher levels of radioactivity were attained in the embryonic vesicles than in maternal plasma at all time intervals tested. Hycanthone also had embryotoxic activity in rabbits. A dose of 25 mg/kg increased the incidence of intrauterine death, and at 50 mg/kg both embryolethal and teratogenic effects were noted.
Evaluation of the teratogenic activity of hycanthone in mice and rabbits
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