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Evaluation of teratogenic potential of N-formylpiperidine in rats
R S Nair1, L Alvarez, F R Johannsen
1Monsanto Company, St. Louis, Missouri 63167.
Abstract:
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.(ABSTRACT TRUNCATED AT 250 WORDS)
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