Developmental Toxicity Potential of Nitroguanidine in Rats
Abstract
The potential of nitroguanidine to produce developmental toxicity was evaluated in pregnant Sprague-Dawley rats. Nitroguanidine, suspended in 1% carboxymethylcellulose, was administered at doses of 0, 100, 316, and 1000 milligrams/kg/day by oral gavage on Days 6 through 15 of gestation. Fetuses were delivered by cesarean section on Day 20, weighed, examined externally, and processed in either Bouin's solution for visceral examination or alizarin red stain for skeletal examination. Following a generalized failure to thrive, two animals in the 1000 milligrams/kg/day group died and one was terminated in a moribund condition. At necropsy, significant quantities of nitroguanidine were present in the stomachs of these three animals. Nitroguanidine given at 1000 milligrams/kg/day produced decreased food consumption, weight loss, dehydration, red urine, and red material on nose/whiskers in the dams during the treatment period and decreased weight gain from Day 0 to Day 20 of gestation. Fetuses from the 1000 milligrams/kg/day group were significantly smaller than controls with an increased incidence of retarded ossification of the sternebrae, caudal vertebrae, pubis. There was no evidence of developmental toxicity of nitroguanidine in rats under conditions of this study. Nitroguanidine produced maternal and fetal toxicity at the 1000 milligrams/kg/day dose level. The no- observed-effect level was 316 milligrams/kg/day. Keywords: Developmental toxicology, Teratology, Nitroguanidine, Rats.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1988
- Accession Number
- ADA192383
Entities
People
- Don W. Korte Jr.
- Gayle A. Orner
- Valerie G. Coppes
Organizations
- Letterman Army Hospital