Abstract |
Groups of 26 mated Wistar rats were treated from gestation days 6 to 19, by gavage, with 0, 80, 500, or 1000 mg/kg/day of JAU 6476 in 0.5% aqueous carboxymethylcellulose. On day 20 of gestation, the fetuses were delivered by cesarean section. Water consumption and urine excretion were dose-dependently increased for the 500 and 1000 mg/kg/day dose groups. There was no affect on body weight or gravid uterine weight, however, there was a dose related statistically significant decrease in the corrected body weight gain for the 500 and 1000 mg/kgiday dose groups. Clinical chemistry conducted on blood collected at the time of the cesarean section revealed decreased thyroxine and increased cholesterol values in the 500 and 1000 mg/kg/day dose groups. Alanine aminotransferase and alkaline phosphatase were slightly increased at the 1000 mg/kg/day dose. With respect to intrauterine development, there was an increased incidence of engorged placentas and slightly lower fetal weight in the 1000 mg/kg/day dose group. Visceral examination of the fetuses revealed an increased incidence of renal pelvis dilation and microphthalmia in the 1000 mg/kg/day dose group. Evaluation of the skeletons revealed a slight increase in incomplete ossification in single skeletal locations and an increased incidence of supernumerany lumbar rib formation in the 1000 mg/kg/day dose group. The data from this study are indicative of a perturbation of embryonic or fetal development, with an increased incidence of skeletal variation, retarded development, and an increase in common malformations at a dose of 1000 mg/kg/day. |