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Scientific Frontiers in Developmental Toxicology and Risk Assessment
curred is the critical factor in determining which organ was affected. The concept of developmental phase specificity and other core principles of experimental developmental toxicology grew out of that early work. Knowledge about normal developmental processes was applied to understand abnormal development, the pathogenesis resulting in malformations. In the course of such investigations, various chemical and physical insults were used to perturb development to elucidate the underlying normal processes.
In the 1950s, approximately at the time when basic scientific research in normal and abnormal embryo development was expanding, phocomelia and amelia of the arms and legs, two very rare manifestations of human limb defects, occurred in infants born in several European countries and Australia. Independently and almost simultaneously, two alert physicians, one in Australia and one in Germany, concluded that the sudden increase in those defects was attributable to treatment with the pharmaceutical thalidomide early in the pregnancies of the mothers of the affected babies (McBride 1961; Lenz 1961; Lenz and Knapp 1962). Until that time, thalidomide was thought to be a “nontoxic” sedative/hypnotic. The removal of thalidomide from the international market brought the phocomelia epidemic to an end. By various estimates, 7,000 to 10,000 babies were affected. Animal studies later confirmed that thalidomide has toxicological properties that affect development in some species (for reviews, see Neubert and Neubert 1997 and Stephens 1988).
Mass media coverage of the thalidomide tragedy brought the field of developmental toxicology to the attention of the public. For the first time, it was tragically demonstrated that a chemical agent had the potential to profoundly affect human development. Responsible scientists and members of the regulatory community recognized that developmental toxicity might not be unique to thalidomide. It was soon realized that the toxicity testing methods for pharmaceutical products in use at that time were focused primarily on the adult and were inadequate to predict the response or susceptibility of the embryo or fetus. An ad hoc committee of scientists, including many of the charter members of the Teratology Society, was assembled by the U.S. Food and Drug Administration (FDA) to develop guidelines for assessing the hazard potential of new therapeutic agents for developmental toxicity. Other regulatory agencies in the United States and around the world have since adopted similar guidelines, which are applied not only to pharmaceuticals but to all classes of chemicals with significant human exposure potential.
The recognition that environmental factors, whether chemical, physical, or biological, could elicit malformations resulted in a new emphasis on identifying and characterizing other agents that might cause adverse impacts. The disciplines of developmental biology, pharmacology, toxicology, and obstetrics and gynecology were brought together to address these research questions. As our ability to understand the cellular and macromolecular actions of chemicals grew, so did the field of developmental toxicology, which increasingly focuses on un-