Chlorcyclizine produced cleft palate in the ferret.

THE SUSCEPTIBILITY of rat and mouse embryos to the teratogenic action of chlorcyclizine has been shown by KING and his co-workers (KING, 1965; STEFFEK, 1966). The spectrum of congenital malformations for both these species included clefts of the secondary palate. The species susceptibility of the ferret, a non-rodent, to this agent was investigated and the results are presented in this report. Ferrets were mated at a commercial source (Gilman Marshall, North Rose, New York) and shipped the following day which was recorded as the first day of gestation. Upon arrival at the laboratory, the pregnant ferrets were maintained with a minimal amount of handling for at least a two week period. The maternal diet during this and the subsequent periods of experimentation consisted of fresh horse meat, beef liver, pulverized chick-egg shell, cod liver oil and homogenized pasteurized milk. On days 14-21, 16-23 and 18-25 of gestation, one cm3 of ground chlorcyclizine tablets in water (30 mg/kg) was administered subcutaneously to the animals. One additional ferret received a similar subcutaneous injection of chlorcyclizine in a dosage of 40 mg/kg from the 15-25 gestational days. The control animals consisted of three groups which received either the same volume of saline (two ferrets), drug excipient (five ferrets) or no injections (three ferrets) during the experimental period. The animals were maintained until day 35 of gestation (7 days before expected parturition) and killed by ether anesthesia. The f&uses were removed by laparotomy and examined for grosscongenital malformations. The results are presented in Table 1. One fcetus exhibiting a spontaneous malformation of exancephaly was obtained from the control non-injected group. No spontaneous malformations were seen in either the sham-injected saline or excipient group. Three spontaneous resorptions were noted in the control non-injected series. Maternal loss of hair and fcetal resorptions were observed in one pregnant ferret treated with 40 mg/kg of chlorcyclizine from the 15th through 25th days of gestation. As the dosage was reduced and the time of drug administration restricted to other