The resolution of links between exposure to components of our complex environmental and causation of reproductive effects in the population constitutes an important problem in the field of toxicology. The focus of this volume is developmental toxicology, which represents one aspect of reproductive toxicology dealing with the study of adverse effects on the developing conceptus. Developmental toxicology, which includes teratogenesis as one of its manifesta­ tions, provides a fertile field for research in several basic and clinical disciplines; this field also receives input from several disoiplines such as developmental and molecu­ lar biology, pathology, pharmacology and toxicology, pediatrics and neonatology, and epidemiology. More recently we h~ve seen an emergence of interest in other fields such as perinatal physiology and postnatal behavior which have now become incorporated into the mainstream of research in this discipline. The present volume is an effort to provide a sampling of concepts currently under active investigation in several of the above fields. The authors have endeavored to provide up-to-date in­ formation on the following topics: detection and analysis of potential hazards to the conceptus in the workplace, pharmacokinetic aspects of the maternal/placental! fetal complex and its relationship to human birth defects, and probable mechanisms of teratogenesis as uncovered in certain well-defined situations. Also included are summaries of newer investigations on the emerging field of postnatal functional evaluations, i. e. , adverse effects on adult activities resultant from in utero exposure to toxic substances.

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Epidemiology and Bioavailability.- 1 Assessment of Potential Hazards to the Unborn in the Workplace.- A. Introduction.- B. Management of the Hazard.- C. Environmental Agents.- D. Protective Measures.- E. Safety Standards.- F. Summary.- References.- 2 Pharmacokinetic Modeling and the Teratologist.- A. Introduction.- B. Pharmacokinetic Modeling and Simulation.- I. One-Compartment Open Model.- II. One-Compartment Model with Parallel Elimination.- III. One-Compartment Absorption Model.- C. Multicompartment Models.- I. Two-Compartment Model.- II. Protein Binding and Metabolism Models.- III. Drug-Chemical Interactions (Blood Protein and Tissue Binding).- D. Data Acquisition and Analysis.- References.- 3 Placental Drug Metabolism.- A. Introduction.- B. Oxidation Reactions.- I. Dehydrogenases.- II. Monoamine Oxidase.- III. Monooxygenases.- C. Reduction Reactions.- D. Hydrolytic Reactions.- E. Conjugation Reactions.- References.- 4 Genetic Differences in Drug Metabolism: Proposed Relationship to Human Birth Defects.- A. Introduction.- I. Phase I and Phase II Drug-Metabolizing Enzymes.- II. Fundamental Aspects of Cytochrome P-450.- III. Assessment of Substrates Metabolized by Cytochrome P-450.- B. The Ah Locus.- I. Genetics.- II. Pleiotypic Response of the Ah System.- C. Genetic Influences on Drug-Induced Birth Defects.- D. Use of Ah Locus for Teratogenesis Studies.- I. Genetic Differences in BaP Teratogenicity.- II. Correlation of BaP-Induced Stillbirths and Resorptions with the Ah Allele.- III. Association of BaP-Induced Embryotoxicity with the Ah Allele.- IV. Correlation of BaP-Induced Teratogenesis with the Ah Allele.- V. Developmental Expression of Ah Allele in the Mouse Embryo.- E. Extrapolation of Data to the Human.- F. Summary.- References.- Mechanisms of Teratogenesis.- 5 Viruses as Teratogens.- A. Introduction.- B. Discussion.- I. Epidemiology.- II. Rubella Virus.- III. Cytomegalovirus.- IV. Herpes Simplex Virus.- V. Venezuelan Equine Encephalitis Virus.- VI. Varicella Virus.- C. Summary.- References.- 6 Hormonal Involvement in Palatal Differentiation.- A. Introduction.- B. Developmental Aspects of Secondary Palate Formation.- C. Cyclic AMP and Palatal Differentiation.- D. Prostaglandins in the Secondary Palate.- E. Summary.- References.- 7 Membrane Lipids and Differentiation.- A. Introduction.- B. Membrane Lipid Composition and Differentiation.- C. Lipids as Intracellular Messengers.- D. Membrane Lipid Metabolism During Normal and Abnormal Mammalian Embryogenesis.- I. Initial Studies.- II. Role of the Placenta.- III. Experimental Approaches.- IV. Results.- 1. In Vitro Enzyme Studies.- 2. In Vivo Metabolic Studies.- 3. In Vitro Metabolic Studies.- 4. Acyl Composition of Embryo and Placental Phospholipids.- V. Vitamin A and Glucocorticoids.- E. Conclusion.- References.- 8 Hormone Receptors and Malformations.- A. Introduction.- B. Steroids.- I. Androgens.- 1. Testicular Feminization.- II. Glucocorticoids.- 1. Cystic Fibrosis.- 2. Cleft Palate.- C. Cholesterol.- I. Low Density Lipoprotein.- 1. Familial Hypercholesterolemia.- D. Thyroid Hormones.- I. Triiodothyronine.- 1. Familial Thyroid Hormone Resistance.- E. Polypeptide Hormones.- I. Growth Hormone.- 1. Levi-Lorain Dwarfism and Snell Dwarf.- II. Parathyroid Hormone.- 1. Pseudohypoparathyroidism.- F. Conclusion.- References.- 9 Mutagens as Teratogens: A Correlative Approach.- A. Introduction.- B. In Vivo Cytogenetics Versus Teratology.- C. In Vitro Cytogenetics Versus Teratology.- D. Teratogenicity and Microtubule Disruption.- E. Carcinogens as Mutagens and Teratogens.- F. Discussion.- I. Teratology Correlated with Chromosome Alteration.- II. Teratology Correlated with Carcinogen-Induced Point Mutations.- III. Mutation and Abnormal Development.- References.- Adverse Effects on Function.- Chpater 10 Behavioral Testing Procedures: A Review.- A. Introduction.- B. Morphological Development of the Central Nervous System.- C. Variables in Behavioral Teratologic Testing.- I. Examples of Behavioral Teratogens.- II. Premating and Prenatal Variables.- III. Postnatal Variables.- D. Postnatal Assessment.- I. Physical Development.- 1. Pinna Detachment.- 2. Incisor Eruption.- 3. Eye Opening.- 4. Ear Unfolding and Opening.- 5. Testes Descent.- 6. Vaginal Opening.- 7. Development of Fur.- II. Behavioral Analyses.- 1. Reflex Development Tests.- 2. Motor and Coordination Tests.- 3. Spontaneous or Nonforced Behavior Tests.- 4. Forced Behavioral Tests.- E. Conclusions.- References.- 11 Behavioral Teratology: A New Frontier in Neurobehavioral Research.- A. Introduction.- B. Agents that Cause Gross Structural Malformation and Behavioral Effects.- I. Animal Studies and the Consideration of Critical Periods.- 1. Predifferentiation Period.- 2. Period of the Embryo.- 3. Period of the Fetus.- II. Human Studies.- 1. The Fetal Alcohol Syndrome.- 2. The Fetal Hydantoin Syndrome.- 3. The Fetal Trimethadione Syndrome.- 4. Thalidomide.- C. Agents that Cause Behavioral Effects in the Absence of Gross Structural Malformations.- I. Animal and Human Studies.- 1. Amphetamine.- 2. Barbiturates.- 3. Phencyclidine.- 4. Opiates.- D. Summary.- References.- 12 Abnormal Lung Function Induced by Prenatal Insult.- A. Introduction.- B. Lung Development.- C. Experimental Alteration of Lung.- D. Impact and Visibility of Developmental Alterations in Neonatal Population.- E. Conclusion.- References.- 13 Postnatal Alterations of Gastrointestinal Physiology, Hematology, Clinical Chemistry, and Other Non-CNS Parameters.- A. Introduction.- B. Functional Teratology of the Gastrointestinal Tract.- I. Gastrointestinal Congenital Malformations.- II. Normal Anatomy, Development, and Physiology of the Gastrointestinal Tract.- III. Physiologic Teratology of the Gastrointestinal Tract.- IV. Test Agents.- V. Observations.- 1. Anatomic.- 2. Rectal Emptying.- 3. Transit Time.- 4. Food Consumption and Utilization.- 5. Gastric Emptying.- VI. Discussion of Observed Physiologic Changes.- C. Other Non-CNS Functional Alterations.- I. Hematology.- II. Clinical Chemistry.- III. Urinalysis.- IV. Reproduction.- V. Cardiovascular.- VI. Organ Weights.- VII. Histopathology.- VIII. Immunology.- D. Summary and Conclusion.- References.- In Vitro Screens of Teratogenic Potential.- 14 Detection of Teratogens Using Cells in Culture.- A.…