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Scientific Frontiers in Developmental Toxicology and Risk Assessment
have also evolved adaptive mechanisms, stress responses, and checkpoint pathways to prevent or correct damage from various environmental chemicals and physical conditions (e.g., heat shock), and hence to survive in their environment. Thanks to the broad specificities of these proteins and adaptive processes, animals also detoxify and adaptively respond to many synthetic chemicals as well, even though the animal has never seen these chemicals before in its evolution. Understanding detoxification and adaptation processes in animals and especially in humans has widespread implications for the field of developmental toxicology (for reviews, see Juchau 1980; Juchau et al. 1980; Shepard et al. 1983). Still, some small fraction of old and new chemicals, synthetic and natural, can elude the animal’s defenses enough to impact components of its developmental processes, thereby leading to developmental defects.
The frequency at which all classes of developmental defects occur is thought to be very high, perhaps exceeding half of initial pregnancies. However, the total frequency of developmental defects is only vaguely known, and the means of surveillance for defects are only approximate. It is thought that among newborns with major developmental defects, genetic transmission accounts for perhaps 25% of the cases. Lesser genetic defects, which are insufficient on their own to cause major defects but are sufficient in combination with environmental factors or other genetic factors, account for perhaps another 25% of major defects. Genotype combined with environmental causes is a class of developmental defect that is expected to receive incisive attention in the near future. Genotype is an important class because of its implications that some environmental agents might act as toxicants for some people (predisposed individuals) but not for others, making risk assessment a process requiring information about human diversity as well as toxicant action. A few percent (approximately 3%) of developmental defects are probably attributable to chemicals and physical agents alone and have no known genetic contribution. An unknown fraction of those are due to environmental toxicants. Finally, the causes of nearly half of the major defects immediately detected at birth are so poorly understood that they cannot even be classified as being caused by intrinsic or extrinsic factors or both. Presumably, some fraction of them have a complex environmental component. At the same time, there is a steadily expanding universe of chemicals and combinations of chemicals to which humans are exposed. Most of these chemicals have never been tested for developmental toxicity.