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 demonstrated in CD rats and New Zealand White rabbits in 3 developmental toxicity studies in each species. Based on dose range-finding studies 1000 or 300 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 and 10. The vehicle control groups received either 1% methylcellulose/0.2% Tween 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 consumption were evaluated. Necropsy and cesarean-section observations were conducted 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 consumption, while fetal toxicity occurred as significantly decreased fetal body weights. RP was teratogenic in both rats and rabbits, producing a spectrum of significantly increased external, skeletal, and visceral fetal anomalies in all RP-treated groups. The observed malformations were typical of those produced by vitamin A, i.e., cleft palate, pinna anomalies, and microphthalmia/anophthalmia. These studies demonstrate that RP is a reproducible and cost-effective positive control agent for use in rat and rabbit developmental toxicity studies.