Developmental Toxicity (Segment II) Study of WR242511 in Rabbits
Abstract
This study evaluated the embryo/fetal toxicity and the teratogenic potential of WR242511 tartrate in time-mated New Zealand White (Pasteurella Free) female rabbits. Doses were 0, 0.5, 1.3, and 3.5 mg base/kg/day administered by gavage during gestation days (GD) 6-18 (GDO = day of observed mating). In addition, a positive control group was administered retinol palmitate, 300 mg/kg/day, on GD9 and 10 by gavage. The results are summarized in Table 1. One female in the high dose prematurely delivered on GD29 and one female in the mid dose aborted on GD27. No other maternal toxic manifestations were observed in any WR242511 dose level. In addition, fetal toxicity was not apparent. In the positive control group, one female aborted on GD22. Other manifestations of toxicity in this group were a marginal decrease in weight gain during dosing; significant decreases in uterine weight and viable fetuses; and significant increases in post-implantation loss, early resorptions and fetuses with external, visceral and skeletal malformations. With the exception of one abortion and one premature delivery in test article-treated animals, toxicity was not apparent in either the does or their fetuses. Based on the results of this study, the highest dose tested (3.5 mg base/kg/day) was considered at or near the no observed effect level for both maternal and fetal toxicity in rabbits. Since 6 mg base/kg/day in a previously conducted dose range-finding study was lethal to 5/5 animals, it is believed that a dose in excess of 3.5 mg base/kg/day in the present investigation would have resulted in excessive mortality.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 02, 1994
- Accession Number
- ADA640607
Entities
People
- Barry S. Levine
Organizations
- University of Illinois at Chicago