CRITICAL PERIODS OF EXPOSURE AND DEVELOPMENTAL OUTCOME

The most unique aspect of the field of developmental toxicology, which sets it apart from all other areas of toxicologic investigation, is t he rapidly changing susceptibility of the conceptus to insult. In this presentation, an overview of the changing susceptibility of the conce ptus will be given, with a discussion of tile difficulties this presen ts for risk assessment. Prenatal development of all mammalian species can be divided up into the preimplantation, embryonic, and fetal perio ds, with each period possessing its own characteristic susceptibility and unique response to prenatal insult. Most developmental toxicity st udies have focused on the embryonic period, with malformations as the outcome of major concern. As understanding of mammalian development ha s increased, it is now clear that susceptibility to functional impairm ents, as well as to physiologic alterations, also exist during the emb ryonic and fetal period, which have major consequences for the offspri ng. The pattern of outcome can vary dramatically depending on the time of exposure; differences in exposure intervals as short as one day ca n result in a shifting of the pattern of malformation and even determi ne whether malformations, embryonic death, or functional impairment oc curs. Consequently, in considering risk assessment for developmental t oxicity, the time of exposure has to be taken into consideration, as w ell as the level of exposure.