Retinyl palmitate as a positive control agent in rat and rabbit developmental toxicity studies

The use of retinyl palmitate (RP) as an oral positive control agent was dem onstrated in CD rats and New Zealand White rabbits in 3 developmental toxic ity studies in each species. Based on dose range-finding studies 1000 or 30 0 mg/kg day(-1) (i.e., 250,000 and 75,000 IU/kg day(-1)) were administered by oral gavage to rats and rabbits, respectively on gestation days (GD) 9 a nd 10. The vehicle control groups received either 1% methylcellulose/0.2% T ween 80 or deionized distilled water from GD 6 to 15 in rats and from GD 6 to 18 in rabbits. Maternal clinical signs, body weights, and food consumpti on were evaluated. Necropsy and cesarean-section observations were conducte d on GD 20 and 29 in rats and rabbits, respectively All viable fetuses were weighed, sexed, and externally examined. In rats but not rabbits, maternal toxicity was observed as significantly decreased body weights and food con sumption, while fetal toxicity occurred as significantly decreased fetal bo dy weights. RP was teratogenic in both rats and rabbits, producing a spectr um of significantly increased external, skeletal, and visceral fetal anomal ies in all RP-treated groups. The observed malformations were typical of th ose produced by vitamin A, i.e., cleft palate, pinna anomalies, and microph thalmia/anophthalmia. These studies demonstrate that RP is a reproducible a nd cost-effective positive control agent for use in rat and rabbit developm ental toxicity studies.