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Oral administration of a large amount of chlormadinone acetate into pregnant mice and rabbits produced a large number of fetal malformations, such as cleft palate and others, while norethisterone with 1% mestranol showed no such teratogenic activity though its lethal effect on the fetuses was stronger than that of chlormadinone acetate. Norethynodrel with 2% mestranol showed the strongest lethal effect of the progestogens tested in mouse embryos, and cleft palate was induced in the surviving fetuses at 10 mg/kg. The dosage of the drugs which showed teratogenicity was generally much higher than human therapeutic or pharmacological doses in rabbits on the basis of maternal body weight.
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Takano et al. (1966) studied this question.
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