Teratogenic effect of 9-fluoro-11β, 21-dihydroxy-16α-methylpregna-1, 4-diene-3, 20-dione (A 41 304), a new antiinflammatory agent, and of dexamethasone in rats and mice

A41 304 at 400 μg/kg produced depression of body weight gains in the rat dams but did not increase the number of the fetuses with gross malformations. At 400 μg/kg of dexamethasone, body weight gains of the rat dams were markedly depressed and fetuses presented cleft palate and depression of the placental weight, body weight and crown-rump length. As for the influence of both drugs upon the fetal skeleton, ossification of the odontoid process and metatarsus was delayed and lumbar ribs increased. Dexamethasone at 400 μg/kg, in addition to these findings, caused prominently delayed ossification of the caudal vertebrae. When A41 304 at 1600 μg/kg and dexamethasone at 400 μg/kg were given to pregnant mice, cleft palate occurred with high incidences, but neither visceral abnormalities nor skeletal malformations attributable to the drug administration were observed. The critical period of cleft palate which was noted in the mice given A41 304 was day 11 through day 15 of pregnancy, mainly days 11 ?? 13 of pregnancy. Cleft palate was seen in a doserelated manner in either A41 304-treated groups or dexamethasone-treated groups, but the incidence at the same dosage level was higher in dexamethasome-treated groups than in A41 304-treated groups.