Morphogenesis of malformations in hamsters caused by retinoic acid: relation to dose and stage at treatment.

Female golden hamsters were each given a single administration of retinoic acid sodium saltat one of 20 stages in pregnancy. Retinoic acid is the carboxylic acid derived by oxidation of the hydroxyl group of retinol (vitamin A1 alcohol). It is rapidly excreted and appears to act for a short time. Near-term fetuses were found to have more than 70 types of malformation. The incidence of each external malformation produced by several oral dosage levels at each of 15 postimplantation treatment times was determined. The incidence of each internal malformation at the fetal LD50 dose was determined. Forty types of malformation whose incidence was 10% or more at the fetal LD50 dose at some time in pregnancy were studied. Embryonic development of various structures was correlated with the critical period for production of each malformation, based on a table of normal development constructed by examining untreated embryos at 48 ages. In many cases the period during which administration of retinoic acid produced a given malformation began well before there was any morphologically identifiable precursor of the structure destined to be affected.