Teratogenic effect of cyclophosphamide and the preventive effects of pyrithinoldehydrochloride monohydrate.

Teratogenic effects were induced in outbred Swiss mice by treatment of 8-week-old pregnant females with one of five different doses (5, 10, 20, 30, 40 mg/kg b.w.) of cyclophosphamide. Because the 11.5th day of pregnancy was the most effective day to induce malformations in mice, animals treated on this day were used for prophylactic studies. A preliminary study had shown that 30 mg/kg b.w. cyclophosphamide was the ideal dose to produce 100% malformations on the 11.5th day of pregnancy. From day 7.5 to 9.5 all fetuses were resorbed with this dosage. Most malformations were induced with 20, 30 or 40 mg/kg b.w., whereas 5 and 10 mg/kg b.w. caused no alterations of the fetuses. The frequency distributions of the various induced malformations and combined malformations of a positive control group (30 mg/kg b.w. of cyclophosphamide on the 11.5th day of pregnancy) were compared to those found in groups receiving different doses of the prophylactic. This substance reduced significantly the rate of malformations; 1/160 LD50 pyrithinoldehydrochloride monohydrate administered 4 times prior to cyclophosphamide treatment was the most effective. However, a complete prevention of teratogenic effects could not be accomplished.