Acute Oral and Intraperitoneal Toxicity Study of WR242511 and WR269410 in Rats
Abstract
This study examined the acute oral and intraperitoneal toxicity of WR242511 tartrate and WR2694I0 in rats. 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. Non-survivors were also necropsied. The acute oral LD50 of WR242511 tartrate in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was approximately eight-fold lower than in female rats (males; 16.3 mg base/kg and females; 135 mg base/kg). The LD50 values obtained when WR242511 tartrate was administered intraperitoneally in the same vehicle were not significantly different between the sexes (males; 32 mg base/kg and females; 30 mg base/kg). Thus, the LD50 of WR242S11 tartrate was unaffected by sex when administered by intraperitoneal injection, but affected by sex when administered orally. The acute oral LDS0 of WR269410 in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was approximately four-fold greater than in female rats (males; 603 mg/kg and females; 147 mg/kg). Due to a physical inability to intraperitoneally administer WR269410 dosage formulations in 0.1% Methylcellulose/O.4% Tween 80 at high enough concentrations to produce lethality, WR269410 was administered intraperitoneally as a solution in polyethylene glycol 200 (PEG 200). The calculated LD50 value of intraperitoneally administered WR269410 in males was 155 mg/kg. An LD50 value in females was estimated to be approximately 70-80 mg/kg. The results of this study suggest that WR242511 tartrate is more acutely toxic than WR269410 when administered either orally or intraperitoneally. Based on the oral LD50 data and after consultation with the Sponsor, the following dose levels are suggested to be used in the two week oral dose range-finding studies in rats of WR242511 tartrate; 0, 0.5, 2.0, and 62 mg base/kg/day, and of WR269410; 0, 2.0, 6.0, 18.0 mg/kg/day.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 14, 1993
- Accession Number
- ADA640628
Entities
People
- Barry S. Levine
Organizations
- University of Illinois at Chicago