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  • History

  • Scope of Problem: The Human Experience

    • Thalidomide

    • Diethylstilbestrol

    • Ethanol

    • Tobacco Smoke

    • Cocaine

    • Retinoids

    • Antiepileptic Drugs

    • Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists

  • Principles of Developmental Toxicology

    • Critical Periods of Susceptibility and Endpoints of Toxicity

    • Dose–Response Patterns and the Threshold Concept

  • Mechanisms and Pathogenesis of Developmental Toxicity

    • Advances in the Molecular Basis of Dysmorphogenesis

  • Pharmacokinetics and Metabolism in Pregnancy

  • Relationships between Maternal and Developmental Toxicity

  • Maternal Factors Affecting Development

    • Genetics

    • Disease

    • Nutrition

    • Stress

    • Placental Toxicity

    • Maternal Toxicity

  • Developmental Toxicity of Endocrine-Disrupting Chemicals

    • Laboratory Animal Evidence

    • Human Evidence

    • Impact on Screening and Testing Programs

  • Modern Safety Assessment

    • Regulatory Guidelines for In Vivo Testing

    • Multigeneration Tests

    • Children’s Health and the Food Quality Protection Act

    • Alternative Testing Strategies

    • Epidemiology

    • Concordance of Data

    • Elements of Risk Assessment

    • New Approaches

      • The Benchmark-Dose Approach

      • Biologically Based Dose–Response Modeling

  • Pathways to the Future

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History

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Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functional or metabolic impairment, and/or death of the organism. Developmental exposures may also alter the risk of diseases in adulthood. Developmental toxicology defined as such is a relatively new science, but teratology, the study of structural birth defects, as a descriptive science preceded written language. For example, a marble sculpture from southern Turkey dating to 6500 bc depicts conjoined twins (Warkany, 1983), and Egyptian wall paintings of human conditions such as cleft palate and achondroplasia date to as long as 5000 years ago. Conjecture has it that mythological figures such as the Cyclops and sirens took their origin in the birth of malformed infants (Thompson, 1930; Warkany, 1977). Ancient Babylonians, Greeks, and Romans believed that abnormal infants were reflections of celestial events and were considered to be portents of the future. Indeed, the Latin word monstrum, from monstrare (to show) or monere (to warn), connotes an ability to foretell the future. In turn, derivation of the word teratology is from the Greek word for monster, teras.

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Hippocrates and Aristotle thought that abnormal development could originate in physical causes such as uterine trauma or pressure, but Aristotle also held a widespread belief that maternal impressions and emotions could influence the development of the child. He advised pregnant women to gaze at beautiful statuary to increase their child’s beauty. Although this theory sounds fanciful, it is present in diverse cultures throughout recorded history. Indeed, we now know that maternal stress, depression, and anxiety during pregnancy can be deleterious to the developing conceptus and child (Dunkel Schetter and Tanner, 2012).

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In 1649, the French surgeon Ambrois Paré expounded upon the theory of Aristotle and Hippocrates by writing that birth defects could result from narrowness of the uterus, faulty posture of the pregnant woman, or physical trauma such as a fall. Fetal limb amputations were thought to result from amniotic bands, adhesions, or twisting of the umbilical cord. This conjecture has proven ...

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