Acute Oral and Intraperitoneal Toxicity Study of WR242511 and WR269410 in Mice
Abstract
This study examined the acute oral and intraperitoneal toxicity of WR242511 tartrate and WR269410 in mice. The dose levels were selected on the basis of range-finding tests. After dosing, the animals were weighed weekly, observed daily for 14 days, and the survivors were necropsied on Day 14. Nonsurvivors were also necropsied. The acute oral LD50s of WR242511 tartrate, administered in 1% methylcellulose/0.4% Tween 80 by gavage, were not significantly different between sexes (males; 23.0 mg base/kg and females; 22.45 mg base/kg). The LD50 values obtained when WR242511 tartrate was administered intraperitoneally in the same vehicle were identical for both sexes (21.82 mg base/kg). Thus, the LD50 of WR242511 tartrate was unaffected by sex or route of administration. Due to dosage formulation problems, WR269410 was administered as a solution in polyethylene glycol 200 (PEG 200). An oral LD50 could not be calculated because of apparent vehicle lethality at the dosing volumes necessary to administer lethal doses of WR269410. The oral LD50 of WR269410 is however estimated to exceed 1000 mg/kg, based on the additive contribution of the vehicle to the mortality observed. In the intraperitoneal acute toxicity test, WR269410 was administered in PEG 200 resulting in a LD50 value of 117.43 mg/kg in males and 190.04 rag/kg in females. Thus, WR269410 is several-fold less acutely toxic than WR242511 tartrate administered by either route. This latter drug also demonstrated a significantly steeper dose-mortality curve.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1993
- Accession Number
- ADA573913
Entities
People
- Barry S. Levine
Organizations
- University of Illinois at Chicago