An analysis of fetotoxicity using biochemical endpoints of organ differentiation

The biochemical differentiation of the brain, lungs, liver, and kidneys of the late gestation rat fetus was examined to characterize the immediate implications of retarded growth on fetal development. Initially, the normative profile of development of the brain (weight, DNA content, and protein content), lungs (weight and surfactant accumulation), liver (weight and glycogen deposition), and kidneys (weight, alkaline phosphatase activity, and protein content) was determined on gestation days 19, 20, 21, and 22 (day 1 = finding of sperm in the vaginal smear). Subsequently, five compounds known to induce fetotoxicity (chlorambucil, methyl salicylate, mirex, nitrofen, and toxaphene) were administered during organogenesis, and the effects on organ differentiation were determined in day 21 fetuses. The effects of fetal growth retardation resulting from exposure to exogenous agents were not equally distributed among the organs studied. The liver and kidney appeared more sensitive to insult by these agents than did the brain and lungs.