Thus, risk assessors are challenged by the problems of extrapolation, interpretation, cost, and speed. Considering the large number of environmental chemicals (both manufactured and naturally occurring chemicals) that are not adequately tested for potential developmental toxicity, scientists have been asked to develop testing approaches that are based on our rapidly expanding knowledge of normal development to provide more timely information with improved predictions for human developmental outcomes. These issues are ongoing challenges in the effort to assess human risk from environmental toxicants.


Developmental biology is the study of normal developmental processes. It begins with descriptions of the sequential events of development, from the formation of the oocyte (the egg precursor) and sperm, to fertilization, then to cell division, morphogenesis (the transformation of egg organization into embryonic organization), organogenesis (the formation of organs), cell differentiation, and embryonic and fetal growth. In its full scope, developmental biology covers the development and growth of the infant, child, and adolescent to the time of reproductive maturity. Developmental biology also describes events in the organism’s spatial dimension (the changing number and position of cells, tissues, and organs) in the vast multicellular population of the embryo and fetus (approximately 1 trillion cells in a newborn infant).

In the past 15 years, remarkable advances have been made in the knowledge of the components, mechanisms, and processes of normal development, primarily as the result of new insights into the molecular biology of development. Developmental biology has become a study of the mechanisms of development at the molecular level, particularly of the interaction of components of intracellular genetic regulatory circuits with components of intercelluar signaling pathways. To cite a few of those insights, it is now known that the trillions of cells of a large mammal such as a human have the same genetic composition (genetic blueprint). As recently reaffirmed by the cloning of Dolly the lamb (Wilmut et al. 1997), the Cumulina mouse family (Wakayama et al. 1998), and a nonhuman primate (Chan et al. 2000), the genetic content of almost all of the cells in an animal does not change from that of the single-celled fertilized egg from which it developed. Despite having the same genes, the cells in an animal differ widely in their appearance, functions, and responses to environmental impacts. At least 300 cell types are recognized in humans (e.g., red blood cells, Purkinje nerve cells, and smooth or striated muscle cells), and the number of cell subtypes at different stages of development and different parts of the body is perhaps tens of thousands. These cell types differ greatly in their ribonucleic acids (RNA) and proteins, reflecting the different combinations of genes they express from the same genomic repertoire). Development can be viewed as evolution’s foremost ac-

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