Critical Periods of Exposure and Developmental Outcome

Abstract

The most unique aspect of the Held of developmental toxicology, which sets it apart from all other areas of toxicologic investigation, is the rapidly changing susceptibility of the conceptus to insult. In this presentation, an overview of the changing susceptibility of the conceptus will be given, with a discussion of the difficulties this presents for risk assessment. Prenatal development of all mammalian species can be divided up into the preim-plantation, embryonic, and fetal periods, with each period possessing its own characteristic susceptibility and unique response to prenatal insult. Most developmental toxicity studies have focused on the embryonic period, with malformations as the outcome of major concern. As understanding of mammalian development has increased, it is now clear that susceptibility to functional impairments, as well as to physiologic alterations, also exist during the embryonic and fetal period, which have major consequences for the offspring. The pattern of outcome can vary dramatically depending on the time of exposure; differences in exposure intervals as short as one day can result in a shifting of the pattern of malformation and even determine whether malformations, embryonic death, or functional impairment occurs. Consequently, in considering risk assessment for developmental toxicity, the time of exposure has to be taken into consideration, as well as the level of exposure.