Oral Fertility and Early Embryonic Development Study of WR242511 Tartrate in Rats
Abstract
This study evaluated the toxic potential of WR242511 Tartrate on reproductive capability in CD male and female rats. WR242511 Tartrate is being developed as an anticyanide agent Doses were based on a three month toxicity study in rats (UIC/TRL Study No. 107) in which mortality and toxicity was seen in males at doses of 4.5 mg/kg/day and on a developmental toxicity study in rats (UIC/TRL Study No. 144) in which maternal toxicity was observed at 8 mg/kg/day. In the present study, doses of 0, 0.3, 1.0, and 3.0 mg base/kg/day were administered by daily gavage to male rats for at least 60 days and to pregnant female rats for 23 - 27 days in sperm-positive animals and for 48 days in sperm-negative females. This included 29 days of dosing prior to cohabitation in males and 15 days of dosing prior to cohabitation in females. Lethality/toxicity was seen primarily in the high dose males; while only toxicity occurred in high dose females. Six of 25 high dose males were sacrificed moribund on day 15 or 21. Clinical signs in these and/or the remaining high dose animals included dark material around the nose, piloerection, hunched posture, and rough coat. Significant reductions in body weights, body weight gains, and food consumption occurred in males primarily at 3 mg base/kg/day. In males at 1 mg base/kg/day, sporadic, nonsignificant reductions in body weight gains contributed to a significant reduction in total body weight gains. Decreased organ weight/brain weight ratios were noted in high dose males for the epididymis, seminal vesicles, and prostate. However, there were no effects on sperm motility, count, or morphology in any group, and no apparent effects on the males' ability to impregnate the females. Females in the 3 mg base/kg/day group exhibited significantly reduced body weights and food consumption during the precohabitation and gestation periods. There were no effects on Cesarean section or estrous cycle parameters in any group.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 21, 1995
- Accession Number
- ADA640655
Entities
People
- Barry S. Levine
- Debra L. Kirchner
- Michael Mercieca
Organizations
- University of Illinois at Chicago