Developmental Toxicity (Segments II) Study of WR238605 Succinate in Rabbits
Abstract
This study evaluated the developmental toxicity of WR238605 Succinate in time-mated New Zealand White (Pasteurella Free) female rabbits. Doses were 0, 2, 7 and 25 mg base/kg/day administered by gavage during gestation days (GD) 6 -18 (GDO = day of observed mating). A positive control group was administered retinol palmitate, 300 mg/kg/day, on GD9 and 10 by gavage. Due to an apparent dosage formulation analysis problem, the high dose was retested at the Sponsor's request. Doses of 0 or 25 mg base/kg/day were administered by gavage during GD6 -18. Due to mortality and reduced food consumption, the dose was lowered to 16 mg base/kg/day on GDI5 -16 (the range of days reflects the study stagger Stan over two days). Maternal toxicity was observed in the initial 25 mg base/kg/day and retest 25/16 mg base/kg/day groups. Abortion and premature delivery occurred in die initial study concommitant with minimally reduced body weight and decreases in food consumption. In the retest, mortality or moribund sacrifice preceded by labored breathing or decreased activity, respectively, was seen at 25 mg base/kg/day; while abortion preceded by blood in the cage pan occurred at the lowered dose of 16 mg base/kg/day. Decreased body weight and/or reduced weight gain and severe reductions in food consumption were noted in the majority of animals in the retest group. In the 7 mg base/kg/day group, one animal aborted; however, there were no alterations in body weight or food consumption. Due to the increased incidence in the 25 and 25/16 mg base/kg/day groups, the abortion in the 7 mg base/kg/day group may be related to administration of WR238605 Succinate. There was no maternal toxicity at 2 mg base/kg/day. Neither embryotoxicity, fetotoxicity, nor teratogenicity was evident at any dose level in the initial or retest WR238605 Succinate-treated groups. Based on these data, the maternal NOEL was at or near 7 mg base/kg/day and the fetal NOEL was 25 mg base/kg/day.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 08, 1995
- Accession Number
- ADA640640
Entities
People
- Ashraf F. Youssef
- Barry S. Levine
- Michael Mercieca
Organizations
- University of Illinois at Chicago