Developmental Toxicity (Segment II) Study of WR238605 Succinate in Rats
Abstract
This study evaluated the developmental toxicity of WR23 8605 Succinate in time-mated CD* female rats. Doses were 0, 3, 10, and 30 mg base/kg/day administered by gavage during gestation days (GD) 6-15 (GD0 = day of vaginal plug) . In addition, a positive control group was administered retinol palmitate, 1000 mg/kg/day, on GD9 and 10 by gavage. Maternal toxicity was observed in the high dose and to a lesser extent in the mid dose. At the high dose, significant decreases in body weight, total weight gain and food consumption were observed throughout the study with rough coat seen in two animals. In addition, enlarged spleen was observed at necropsy in 16 high dose and 1 mid dose females. In the mid dose, marginal decreases in body weight and food consumption were observed during the dosing period. Maternal toxicity was not observed in the low dose. Doses of WR238605 succinate used in the present study were not developmentally toxic. Retinol palmitate (1000 mg/kg/day on GD 9 & 10) was developmentally and maternally toxic. Significant decreases in body weight, total weight gain and uterine weights were observed. In addition, significant increases in fetal malformations and decreases in fetal body weights and the number of viable fetuses were observed. In conclusion, WR238605 succinate was maternally toxic in rats at 10 mg base/kg/day, however developmental toxicity was not observed up to 30 mg base/kg/day, the highest dose level tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 04, 1994
- Accession Number
- ADA640741
Entities
People
- A. F. Youssef
- Barry S. Levine
- M. Mercieca
Organizations
- University of Illinois at Chicago