Long-Term Administration of High Dose Vitamin A to Rats Does Not Cause Fetal Malformations: Macroscopic, Skeletal and Physicochemical Finds

A rat model was used to investigate whether high oral doses of vitamin A lead to fetal malformations and to what extent retinyl esters (RES) are transferred from the mother to the fetuses. Retinol and RES concentrations in plasma behave similarly in rats and humans. When high concentrations of vitamin A are administered, plasma retinol concentrations remain relatively constant, whereas plasma RES increased in parallel with the dose. To achieve an elevation from approximately 150 to > 1525 nmol x L(-1) in the experimental group before mating, female Ibm: RORO (spf) rats were fed a maintenance diet enriched with 15.2 x 10(3) retinol equivalents (RE) x kg(-1) at the start and increased stepwis…