Teratogenesis and Reproductive Toxicology

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. Introduction.- B. Differentiating Cells in Culture to Detect Teratogens.- C. In Vitro Cell Interactions.- D. Migration of Cells in Culture.- E. Conclusions.- References.- 15 Embryonic Organs in Culture.- A. Introduction.- B. Advantageous Features of In Vitro Systems.- C. Developmental Features of the Limb Bud.- D. Limb Bud Organ Culture.- I. General.- II. Details of the Culture Method.- III. Characteristics of the Cultured Limb Buds.- IV. Quantification of Cartilage in Cultures.- V. The Use and Efficacy of the Screening System.- VI. Summary.- E. Current Limitations and Future Improvements.- F. Conclusions.- References.- 16 Whole Embryos in Culture.- A. Introduction.- B. Preimplantation.- I. General Considerations.- II. The All-or-None Response.- C. Peri-Implantation.- I. General Considerations.- II. Technical Obstacles.- III. Blastocyst Cultures.- D. Postimplantation.- I. Direct Additions.- 1. Chemical Inhibitors.- 2. Environmental Factors.- 3. Substances Implicated in Human Exposure.- II. Beyond Direct Additions.- 1. Chemical Inhibitors.- 2. Heavy Metals.- 3. Nutrition.- III. Metabolic Activation.- IV. Teratogen Identification.- 1. Diabetes.- 2. Immunologic Responses.- 3. Fetal Wastage.- References.- 17 The Role of an Artificial Embryo in Detecting Potential Teratogenic Hazards.- A. Introduction.- B. Basic Aspects of Hydra Biology.- I. Nurture of Adult Hydra.- II. The Nature of Artificial Hydra “Embryos”.- 1. The Testing Procedure.- a) “Embryos”.- b) Adult Hydra.- C. Evaluation of Results.- D. Discussion.- References.- Chemical Index.