Dose Range-Finding Developmental Toxicity Study of WR242511 in Rats
Abstract
This dose range-finding study evaluated the developmental toxicity of WR242511 tartrate in time-mated CD* female rats. Doses were 0. 0.5, 1,2,4 and 8 mg base/kg/day administered by gavage during gestation days (GD) 6-15 (GD0 = day of vaginal plug). Maternal toxicity was observed at the high dose as a significant decrease in total weight gain. In addition, significant decreases in mean daily food consumption were seen during the treatment period. Rough coat was also observed in three females during GDI3-15. The 4 mg base/kg/day dose was considered near or at the maternal no observable effect level (NOEL). Fetal toxicity was apparent at 8 mg base/kg/day as significant decreases in body weights were seen. At the 4 mg base/kg/day dose, a biologically significant decrease in fetal mean body weights was observed, but was only statistically significant in female fetuses. However, at 1 mg base/kg/day a statistically significant decrease was present in both sexes. No biological differences in any other fetal parameters were observed at the high dose or mid high dose groups vs. the control group. The absence of an effect on fetal body weights at 2 mg base/kg/day could not be explained. Fetal body weight changes at 8 mg base/kg/day were considered due to and/or associated with maternal toxicity. The 1 mg base/kg/day dose was considered at or near the low observable adverse effect level (LOAEL) for fetal toxicity Accordingly the following doses are recommended for the definitive developmental toxicity (Segment II) study in rats: 0, 0.5, 2 and 8 mg base/kg/day.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 06, 1994
- Accession Number
- ADA640561
Entities
People
- Ashraf F. Youssef
- Barry S. Levine
Organizations
- University of Illinois at Chicago