Oral Fertility and Early Embryonic Development Study of WR6026 Dihydrochloride in Rats
Abstract
This study evaluated the toxic potential of WR6026 Dihydrochloride on reproductive capability in CD" male and female rats. WR6026 Dihydrochloride is being developed as an antileishmanial agent. Doses of 0, 3.0, 7.5, and 18 mg base/kg/day were selected on the basis of dose range-finding and developmental toxicity studies in female rats (UIC/TRL Study Nos. 170 and 171, respectively) and a three month toxicity study with a three month recovery period in male and female rats (UIC/TRL Study No. 091). In the present study, doses of 0, 3.0, 7.5, and 18 mg base/kg/day were administered by daily gavage to male CD* rats for at least 54 days and to pregnant female CD* rats for 22 - 26 days in sperm-positive animals and for 33 days in sperm-negative females subsequently palpated pregnant. This included 29 days of dosing prior to cohabitation in males and 15 days of dosing prior to cohabitation in females. One mid dose female was found dead on precohabitation day 13 in the absence of clinical signs and necropsy observations. No mortalities occurred in the high dose. Toxicity occurred in males at 18 mg base/kg/day and in females at 7.5 and 18 mg base/kg/day. Cyanosis seen as blue tongue was observed in both sexes at the high dose. Significantly reduced food consumption and body weights were noted in males at 18 mg base/kg/day essentially throughout the entire study. Decreased organ to brain weight ratios were noted in high and mid dose males for the epididymis. There were no treatment-related effects on sperm motility, count, or morphology in any WR6026 Dihydrochloride-treated group, and no apparent effect on the males' ability to impregnate the females. Females at 7.5 and 18 mg base/kg/day had significant reductions in food consumption and body weight gains during me precohabitation phase. Significantly reduced body weights continued during the gestation phase in females at the high dose.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 09, 1996
- Accession Number
- ADA640650
Entities
People
- Barry S. Levine
- Debra L. Kirchner
- Michael Mercieca
Organizations
- University of Illinois at Chicago