Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Rats. Volume 2 of 3
Abstract
This study evaluated the toxicity of WR238605 in rats following thirteen weeks of daily oral (gavage) administration. A thirteen week recovery period was included for all groups. Dose levels studied were 0 (vehicle control), 0.5, 6 and 18 mg base/kg/day. The primary toxic affects were seen in the RBCs, lungs, and liver. Significant methemoglobin production was observed in mid and high dose animals, but was reversible. Microscopic lesions in the spleen, kidney, and bone marrow were secondary to mild hemolytic anemia. Toxicity again was limited to the two highest dose levels. Decreased food consumption, decreased body weight gains, methemoglobin production and mild anemia were observed at the mid and high dose levels, but were readily reversible after treatment cessation. Increases in serum ALT, AST, and/or LDH and decreased A/G ratios in high dose animals and possibly mid dose males suggested mild hepatotoxicity, however histopathologic lesions were not seen. Leukocytosis possibly secondary to stress and consisting of increased number of lymphocytes, mature neutrophils, and/or monocytes was seen in the treatment period at the two highest dose levels and was reversible after cessation of treatment. Because the aforementioned toxic responses were limited to mid and high dose animals, a no-adverse effect level of WR238605 was assessed to be 0.5 mg base/kg/day.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 18, 1993
- Accession Number
- ADA640540
Entities
People
- Barry S. Levine
- Michael J. Tomlinson
Organizations
- University of Illinois at Chicago