The role of metabolism in the testing of developmental toxicants

The delivery of potential developmental toxicants to the conceptus is dependent on several metabolic and pharmacokinetic factors. Within the maternal-embryo/fetal unit, maternal, placental, and embryo/fetal factors must be considered. These factors include blood flow, permeability, biotransformation, and elimination. Pharmacokinetic models based on data gathered from appropriate in vivo and in vitro studies may be used to describe the effect of these factors on toxicant delivery to the conceptus. Several known human developmental toxicants are discussed in terms of the metabolic and pharmacokinetic factors controlling their delivery to the conceptus. Metabolic events, including activation and/or detoxification, have been reported for the majority of the toxicants examined. Thus it would appear that the role of metabolism should be considered during the testing of potential developmental toxicants.