Two Week Oral Dose Range-Finding Toxicity Study of WR242511 in Rats
Abstract
This study evaluated the toxicity of WR242511 tartrate in rats following two weeks of daily oral administration by gavage. Dose levels studied were 0 (vehicle control), 0.5, 2.0 and 6.2 mg base/kg/day. The primary toxic effects of WR242511 tartrate included anemia, hepatotoxicity and leukocytosis. Females were more sensitive than males to the anemic state whereas the reverse was true for hepatotoxicity. Anemia was seen in mid and high dose females, whereas hepatotoxicity was only observed in high dose males and may have been associated with the death of one high dose male on Day 13. Generalized leukocytosis occurred in the high dose animals and in mid dose females. Toxicity was not apparent in low dose animals. Significant methemoglobinemia was noted in mid and high animals, and possibly at the low dose. As this is the desired pharmacologic effect of WR242511 tartrate, its occurrence was not considered indicative of toxicity. The purpose of mis study was to select dose levels for a three month toxicity study in rats. It is anticipated that significant toxicity would occur at the high dose, marginal or no toxicity would be observed at the mid dose, and no toxicity would occur at the low dose level. On this basis, the following three dose level ranges are suggested: 0.5, I - 1.5, and 2 - 4.5 mg base/kg/day.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 08, 1993
- Accession Number
- ADA640639
Entities
People
- Barry S. Levine
Organizations
- University of Illinois at Chicago