© 1992 Oxford University Press
research-article |
Evaluation of Teratogenic Potential of N-Formylpiperidine in Rats
*Monsanto Company 800 North Lindbergh Boulevard, Sr. Louis, Missouri 63167
E. I. du Pont de Nemours & Company Inc., Haskell Laboratory Elkton Road, Newark, Delaware 19711
Received January 28, 1991; accepted July 8, 1991
Evaluation of Teratogenic Potential of N-Formylpiperidine in Rats. NAIR, R. S., ALVAREZ, L., AND JOHANNSEN, F. R. (1992). Fundam. Appl. Toxicol. 18, 96–101.
The teratogenic potential of a versatile solvent, N-formylpiperidine (NFP), was evaluated in the rat. Three groups of 25 mated female Sprague-Dawley rats were given 110, 220, or 440 mg/kg/day NFP in distilled water by gavage on Days 6 through 20 of gestation. A control group of 25 animals received distilled water on a comparable regimen. Maternal animals were observed daily for signs of toxicity; body weights and food consumption were measured at regular intervals throughout the study. All animals were euthanized on Gestation Day 21 and the fetuses examined for cleft palate and external abnormalities. One-half of the fetuses in each litter were examined for visceral anomalies while the remaining fetuses were examined for skeletal malformations after appropriate staining. One female in the high dosage group died on Gestation Day 12. Clinical signs of toxicity, observed in 6 females in the high dosage group, included tremors, convulsive movements, and an apparent weakness of the legs. Maternal toxicity, in terms of significantly decreased body weight and food consumption, was observed in the mid and high dosage groups. Food consumption was also significantly depressed for the first 4 days of dosing in the low dosage group. There was a significant increase in number of resorptions in the high dosage group when compared to controls. No effects were observed on other reproductive parameters. Mean fetal body weight was significantly lower in the high dosage group when compared to controls. While the incidence of fetal malformations on a litter basis was higher in the high dosage group, this change was not statistically significant. The incidence of ossification variations was also higher in the high dosage group. Thus, a dosage of 440 mg/kg NFP produced maternal toxicity, embryolethality, fetal growth retardation, and an increased number of malformations. Maternal body weights were depressed at 220 mg/kg but no embryo- or fetotoxicity was observed at or below 220 mg/kg NFP. The number and type of fetal malformations in the 110 and 220 mg/kg dosage groups were also comparable to controls. In conclusion, NFP produced fetal effects only at 440 mg/kg, a dosage which resulted in marked toxicity to the dams.