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A comprehensive understanding of toxicologic pathology is essential for those in industry, academia, and government who make decisions concerning the safety and efficacy of drugs and chemicals. Toxicologic pathology relies heavily on the fields of both toxicology and pathology, which are well covered individually in various texts and references; however, there are few texts that address the field of toxicologic pathology. The Handbook of Toxicologic Pathology fills this void and is thus essential for all health professionals within or interacting with the field of toxicologic pathology.
This two-volume set provides the reader with a single reference for toxicologic pathology. In volume I, the book covers toxicologic pathology in its basic aspects, including its definition, the basic biochemical and morphologic mechanisms underlying the discipline, the basic practice of toxicologic pathology (including special techniques) and issues essential to the understanding of toxicologic pathology such as risk assessment, experimental design, and statistical analysis. Next, the book moves to specific issues affecting the "practice" toxicologic pathology, including issues such as knowledge management, regulatory affairs and writing pathology reports. Finally, Volume I closes with several chapters that deal with specific classes of environmental toxicants such as endocrine disruptors and heavy metals. Volume II addresses the toxicologic pathology in a thoroughly standardized systems manner, addressing the basic structure and function of a particular organ system, its response to toxic injury, mechanisms of injury and methods of evaluation of such injury.

Reviews

"The 2 volumes are excellent companions that complement each other as a "1,2" punch! This publication should be on the bookshelf of clinical toxicologists, environmental professionals and laboratory investigators..." ?VETERINARY AND HUMAN TOXICOLOGY (October 2002) "...gives an excellent overview of the numerous processes associated with toxicologic pathology as used in risk assessment. It stands alone as a classic textbook in toxicology, or would be an excellent supplement to other such books. ...Its readability will allow acceptance to all scientists ranging from undergraduate to experienced industry/regulatory professional." ?Paul Baldrick for THE BRITISH TOXICOLOGY SOCIETY NEWSLETTER (Spring 2002) "...very readable, well-referenced, and current... an excellent book for research training." --DOODY'S

"[W]ell illustrated with good quality diagrams, colour and black and white photographs…. [A]n excellent, eminently readable book to have as a study or reference book, covering the essential basics and providing a good overview for any toxicological pathologist, toxicologist or research scientist with an interest in the pathological changes seen in toxicological studies."--British Toxicology Society Newsletter

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[Volume. 1]----------
CONTENTS
VOLUME 1 General Toxicologic Pathology
Contributors = xxv
Preface = xxix
PART A : Basics of Toxicologic Pathology
 1. Toxicologic Pathology : An Introduction / Colin G. Rousseaux ; Wanda M. Haschek ; Matthew A. Wallig
  Ⅰ. An Overview of Toxicologic Pathology = 3
   A. What Is Toxicologic Pathology? = 3
   B. The Philosophy of Toxicologic Pathology = 4
  Ⅱ. The Need for Toxicologic Pathology in Modern Society = 5
   A. What Led to the Need for Toxicologic Pathology? = 5
   B. The Value of Toxicologic Pathology = 9
  Ⅲ. The Future of Toxicologic Pathology = 9
   A. Animals and Toxicologic Pathology = 9
   B. The "Practitioner" of Toxicologic Pathology = 10
   C. The "Researcher" in Toxicologic Pathology = 11
   D. The "Consultant" in Toxicologic Pathology = 12
   E. The "Manager" in Toxicologic Pathology = 12
   F. Training Future Toxicologic Pathologists = 13
  Ⅳ. Summary = 14
   Suggested Reading = 14
 2. Biochemical Basis of Toxicity / Elizabeth H. Jeffery
  Ⅰ. Introduction = 15
  Ⅱ. Absorption = 16
   A. Passage across Membranes = 16
   B. Absorption Routes = 17
  Ⅲ. Distribution = 18
   A. Volume of Distribution = 18
   B. Storage = 18
   C. Barriers = 20
  Ⅳ. Biotransformation = 20
   A. Detoxification and Bioactivation = 20
   B. Role of Enzyme Location in Toxicity = 23
  Ⅴ. Excretion = 23
   A. Urinary Excretion = 23
   B. Mechanisms of Urinary System Toxicity = 24
   C. Biliary Excretion = 25
   D. Pulmonary Excretion = 26
   E. Other Excretory Mechanisms = 26
  Ⅵ. Factors Causing Variation in Handling = 27
   A. Genetic Factors = 27
   B. Environmental Factors = 28
  Ⅶ. Interaction of Agent and Organism = 29
   A. Site Specificity = 29
   B. Dose Dependency and Site of Action = 29
   C. Critical Organ for Toxicity = 30
   D. Temporal Outcome of Interaction = 30
  Ⅷ. Site-Specific Interactions = 30
   A. Receptors and Enzymes = 30
   B. Mechanisms of Site-Specific Toxicities = 32
  Ⅸ. Nonspecific Interaction = 33
   A. Electrophiles and Covalent Binding = 33
   B. Free Radicals and Lipid Peroxidation = 34
   C. Loss of Calcium Homeostasis = 34
  Ⅹ. Mechanisms of Protection = 35
   A. Prevention of Toxicity = 35
   B. Adaptation of the Organism = 35
   C. Reversibility of Toxic Injury = 36
   Suggested Reading = 37
 3. Morphologic Manifestation of Toxic Cell Injury / Matthew A. Wallig
  Ⅰ. Introduction = 39
   A. Key Cellular Components in Cell Injury = 39
   B. Factors Influencing Injury = 39
   C. Reaction of the Body to Injury = 41
   D. Adaptation = 41
  Ⅱ. Reversible Cell Injury = 43
   A. Cell Swelling = 45
   B. Fatty Change = 46
  Ⅲ. Irreversible Cell Injury = 48
   A. Oncotic Necrosis = 49
   B. Apoptotic Necrosis = 56
   C. Sequelae = 58
  Ⅳ. Concluding Comments = 63
   Suggested Reading = 64
 4. Organelle Biochemiry and Regulation of Cell Death / Myrtle A. Davis ; Elizabeth H. Jeffery
  Ⅰ. Overview and Nomenclature = 67
  Ⅱ. Cell Membrane = 68
   A. Introduction = 68
   B. Membrane Integrity and Signals for Engulfment during Apoptosis = 68
   C. Receptors Associated with the Cell Membrane = 68
  Ⅲ. Cytoskeleton = 69
   A. Actin Microfilaments = 70
   B. Microtubules = 70
   C. Intermediate Filaments = 71
   D. Structure Meets Gene Expression and Cell Signaling = 71
  Ⅳ. Mitochondrion = 71
   A. Mitochondrial Compartments and Membranes : History and Function = 71
   B. Permeability Transition Pore(Mitochondrial Megachannel Port) = 72
   C. Mitochondrial Swelling, Permeability, and Mechanism of Cell Death = 72
   D. Mitochondrial Protein Translocation and Apoptosis = 73
   E. Mitochondrial Energy Transport and Cell Death = 73
  Ⅴ. Endoplasmic Reticulum = 74
   A. The "Unfolded Protein Response" to ER Stress = 74
   B. ER Stress and Calcium = 75
   C. Caspase 12 Specifically Responds to ER Stress = 75
  Ⅵ. Nucleus = 75
   A. A Review of Nuclear Structure during Cell Death = 76
   B. Nuclear Structure during Cell Death = 76
   C. Regulation of Cell Death by Nuclear Transcription Factors = 77
   D. DNA Tumor Viruses and Regulation of Apoptosis = 78
  Ⅶ. Extracellular Matrix = 79
   A. Integrins : Cell-Matrix Interaction = 79
   B. Matrix Proteases in Cell Death = 80
  Ⅷ. Summary = 80
   Suggested Reading = 80
 5. Carcinogenesis / Stephen Mastorides ; R. R. Maronpot
  Ⅰ. Introduction = 83
  Ⅱ. The Spectrum of Proliferative Lesions = 84
   A. Quantitative Cell Proliferation = 84
   B. Qualitative Cell Proliferation = 86
   C. Preneoplasia = 87
   D. Neoplastic Cell Proliferation = 88
   E. Diagnostic Distinction among Preneoplasia, Benign Neoplasia, and Malignant Neoplasia = 89
  Ⅲ. Steps in the Neoplastic Process = 90
   A. Overview = 90
   B. Multiple Steps in the Neoplastic Process = 91
  Ⅳ. Hypotheses of Mode of Action of Chemical Carcinogens = 97
   A. Overview = 97
   B. Mutational Genetic Hypothesis of Chemical Carcinogenesis = 98
   C. Nonmutational Genetic Hypothesis of Chemical Carcinogenesis = 100
   D. Epigenetic Hypothesis of Chemical Carcinogenesis = 101
   E. Viral Hypothesis of Carcinogenesis = 104
  Ⅴ. Oncogenes and Tumor Suppressor Genes in Chemical Carcinogenesis = 106
   A. Genes and Tumor Suppressor Genes in Chemical Carcinogenesis = 106
   B. Protooncogene Function = 106
   C. Protooncogene Activation = 107
   D. Protooncogene Activation in Chemical Carcinogenesis = 108
   E. Tumor Suppressor Genes and Carcinogenesis = 110
  Ⅵ. Cell Cycle Control and Carcinogenesis = 110
  Ⅶ. Tests for Carcinogenic Potential of Chemicals = 112
   A. In Vivo Chronic Rodent Carcinogenicity Studies(Rodent Bioassays) = 113
   B. Additional in Vivo Tests for Carcinogenicity = 115
   C. In Vivo Short-Term Tests = 119
   Suggested Reading = 119
 6. Applied Clinical Pathology in Preclinical Toxicology Testing / G. S. Smith ; R. L. Hall ; R. M. Walker
  Ⅰ. Introduction = 123
  Ⅱ. Hematology = 125
   A. Parameters Generally Included in Study Protocols = 125
   B. Interpretative Hematology = 126
  Ⅲ. Clinical Chemistry = 131
   A. Cholesterol, Triglycerides, and Glucose = 131
   B. Serum Proteins = 132
   C. Indicators of Hepatic Integrity and Function = 135
   D. Indicators of Renal Function = 138
   E. Electrolytes = 139
   F. Calcium and Inorganic Phosphate = 139
   G. Enzymes of Muscle Origin = 139
  Ⅳ. Microsomal Enzyme Induction = 140
  Ⅴ. Urinalysis = 141
  Ⅵ. Clinical Pathology Study Design Considerations = 142
  Ⅶ. Clinical Pathology Result Interpretation = 143
   A. Potential Effects of Factors Unrelated to Test Article Treatment = 143
   B. Comparators : Concurrent Controls Reference Ranges = 146
   C. Statistical Analyses = 146
   D. Treatment-Related versus Incidental Findings = 147
   E. Direct versus Indirect Effects = 148
   F. Pharmacologic versus Toxic Effects = 149
   G. Biologic Importance of Treatment-Related Effects = 149
  Ⅷ. Reporting of Clinical Pathology Findings = 150
  Ⅸ. Overall Result Reporting = 151
  Ⅹ. Summary = 151
   Suggested Reading = 152
 7. Nomenclature / Ronald A. Herbert ; James R. Hailey ; John C. Seely ; Cynthia C. Shackelford ; Michael P. Jokinen ; Jeffrey C. Wolf ; Gregory S. Travlos
  Ⅰ. Introduction = 157
  Ⅱ. Terminology Issues = 157
   A. Training = 158
   B. Multiple Pathologists = 158
   C. Diagnostic Drift = 159
   D. Lesion Complexity = 159
   E. The Need for Standardized Nomenclature = 160
   F. Data Collection = 160
  Ⅲ. Suggested Practices = 162
  Ⅳ. Summary = 165
   Suggested Reading = 166
PART B : The Practice of Toxicologic Pathology
 8. Basic Techniques / Thomas J. Bucci
  Ⅰ. Introduction = 171
  Ⅱ. Factors Influencing the Evaluation of Altered Morphology = 172
   A. Collection and Processing of Tissue = 174
   B. Factors Intrinsic to the Animal = 176
   C. Factors Related to the Environment = 178
   D. Factors Related to Nomenclature = 180
  Ⅲ. Summary = 182
   Suggested Reading = 183
 9. Managing Pitfalls in Toxicologic Pathology / Peter C. Mann ; Jerry F. Hardisty ; Mary D. Parker
  Ⅰ. Introduction = 187
  Ⅱ. Study Design = 187
  Ⅲ. Necropsy = 189
  Ⅳ. Histology = 190
   A. Specialized Histologic Techniques = 192
   B. Artifacts versus Lesions = 193
   C. Lesion Interpretation = 196
  Ⅴ. Computer Systems = 202
  Ⅵ. Peer Review = 205
   A. Study Review = 205
   B. Pathology Working Groups = 205
  Ⅶ. Conclusions = 206
   Suggested Reading = 206
 10. Special Techniques in Toxicologic Pathology / N. Gillett ; C. Chan ; C. Farman ; P. Lappin
  Ⅰ. Introduction = 207
  Ⅱ. Immunohistochemistry in Toxicologic Pathology = 207
   A. Introduction = 207
   B. Technical Considerations = 208
   C. Applications of Immunohistochemistry in Toxicologic Pathology = 210
   D. Conclusion = 216
  Ⅲ. In Situ Hybridization = 217
   A. Introduction = 217
   B. Technical Considerations = 217
   C. Applications of ISH in Toxicologic Pathology = 219
   D. Conclusions = 221
  Ⅳ. Flow Cytometry = 221
   A. Introduction = 221
   B. Application of Flow Cytometry in Toxicologic Pathology = 222
   C. Limitation of Flow Cytometry = 226
   D. Laser Scanning Cytometry = 227
   E. Conclusions = 227
  Ⅴ. In Situ Polymerase Chain Reaction(PCR)／in Situ Reverse Transcriptase-PCR = 227
   A. Introduction = 227
   B. Technical Considerations = 228
   C. Controls = 229
   D. Limitations = 229
  Ⅵ. Laser Capture Microdissection = 230
  Ⅶ. Confocal Microscopy = 231
  Ⅷ. Stereology = 232
   Suggested Reading = 233
 11.Application of New Technologies to Toxicologic Pathology / Bruce D. Car ; Paul J. Ciaccio ; Nancy R. Contel
  Ⅰ. Introduction = 243
  Ⅱ. Genomics : High-Density Nucleic Acid Microarrays = 244
  Ⅲ. Proteomics = 246
  Ⅳ. Metabonomics : Pattern Recognition Nuclear Magnetic Resonance Specroscopy = 247
  Ⅴ. Laser Capture Microscopy = 248
  Ⅵ. Computational Modeling = 249
  Ⅶ. Summary = 249
   Suggested Reading = 249
 12. Issues in Laboratory Animal Science for the Toxicologic Pathologist / Jeffrey I. Everitt ; David C. Dorman
  Ⅰ. Introduction = 251
  Ⅱ. Regulatory Issues = 252
   A. Overview of Rules and Regulations = 252
   B. Institutional Animal Care and Use Committee = 253
   C. Methods of Euthanasia = 254
  Ⅲ. Selection of Animal Models = 254
   A. Overview = 254
   B. Genetic Issues = 255
   C. Issues Involving the Use of Historical Databases = 256
   D. Challenges of Genetically Engineered Rodents = 257
  Ⅳ. Animal Health Considerations = 258
   A. Adventitious Agents = 258
   B. Sentinel Monitoring Programs = 259
   C. Microbial Effects on Toxicity = 259
  Ⅴ. Housing and Hubandry Issues = 260
   A. Role of Environment in Lesion Production = 260
   B. Study Design Consideration = 261
  Ⅵ. The Role of Diet in Toxicology Studies = 262
   A. Introduction = 262
   B. Types of Diets = 263
   C. Contaminant Issues = 264
   D. Dietary Optimization = 264
  Ⅶ. Summary = 265
   Suggested Reading = 265
 13. New Animal Models in Toxicology / Eugenia Floyd
  Ⅰ. Many Strains of Genetically Engineered Rodents Are Available for Use in Toxicology = 269
  Ⅱ. Genetically Engineered Mice Can Be Used for in Vivo Genetic Toxicity Testing = 270
   A. Mutamouse and Big Blue Transgenic Mice = 270
   B. Aprt-Deficient Mice = 271
   C. $$P^un$$ Mutant Mice = 272
   D. Other New Models for Mutagenicity Testing = 272
   E. Advantages and Disadvantages of Gene-Altered Mice for Genetic Toxicology = 272
  Ⅲ. Genetically Engineered Mice Can Be Used to Study Mechanisms of Toxicity in Vivo = 273
   A. Role of Xenobiotic Receptors in Toxicity = 273
   B. Role of Cytochrome P450 Enzymes in Toxicity and Carcinogenesis = 274
   C. Role of Phase Ⅱ and Other Metabolic Enzymes in Toxicity and Carcinogenesis = 275
   D. Role of Oxidative Stress in Toxicity = 276
   E. In Vivo Study of Redundancy in Antioxidant Pathways = 277
   F. Role of Cytokines and Other Mediators of Inflammation in Toxicity = 278
  Ⅳ. Genetically Modified Mice Can Be Used for Special or Customized Toxicity Testing = 279
   A. Altered Phenotypes Reflecting Toxicity = 279
   B. Identifying Activity-Related Toxicity = 280
   C. Characterizing Human- Target-Specific Toxicity = 281
  Ⅴ. Genetically Engineered Mice Can Be Useful for Short-Term Carcinogenicity Testing = 281
   A. Multistep Theory of Cancer as Basis for New Models = 281
   B. Global Collaboration to Evaluate Models for Short-Term Carcinogenicity Testing = 282
   C. The Trp53 Hemizygous Model = 282
   D. The TG.AC Mouse = 286
   E. The RasH2 Mouse = 289
   F. Xpa-null and Xpa-null／Trp53 Hemizyogous Mice = 291
   G. The Neonatal Mouse Assay and Other Alternative Carcinogenicity Assays = 292
   H. Current and Future Use of Genetically Modified Mice for Short-Term Carcinogenicity = 293
  Ⅵ. Caveats Apply to the Use of Genetically Engineered Mice in Research = 293
   A. Effects of Genetic Background on Phenotype = 294
   B. Effects of Genetic Technologies on Phenotype = 294
   C. Importance of Genetic Quality Control = 295
  Ⅶ. New Gene-Altering Technologies Will Produce More Sophisticated Mouse Models = 296
   A. Models with Multiple Genetic Alterations = 296
   B. Inducible Transgene Systems = 296
   C. Tissue-Specific Genetic Alterations = 297
   D. Future Models for Use in Toxicology = 298
   Suggested Reading = 299
 14. Pathology Issues in the Design of Toxicology Studies / Ricardo Ochoa
  Ⅰ. Introduction = 307
   A. Toxicology Studies and Their Utility = 307
  Ⅱ. Landmarks in Compound Development = 308
   A. Approval for Human Clinical Trials = 308
   B. Application for a License to Market a Drug = 308
  Ⅲ. The Role of the Pathologist in Compound Development = 309
   A. Discovery Studies = 310
  Ⅳ. Regulatory Studies = 313
   A. Studies to Support First in Human Exposure = 313
   B. Studies to Support Longer Exposures in Humans = 313
   C. Length of Studies = 313
  Ⅴ. General Consideration for the Use of Pathology in Regulatory Studies = 314
   A. What Is in a Diagnosis? = 314
   B. Peer Reviews and Quality Control = 315
   C. Sharing Studies = 316
   D. Recutting and Restaining = 316
   E. Evaluating Only High-Dose and Control Groups = 316
  Ⅵ. Studies to Support First in Human Exposure = 316
   A. Acute Toxicity Studies = 317
   B. Alternative Studies to Support "First in Human" Exposure = 318
   C. Subacute, Subchronic, and Chronic Toxicity Studies = 318
   D. Carcinogenicity Studies = 319
  Ⅶ. Clinical Pathology = 324
  Ⅷ. Reproductive Toxicology = 324
  Ⅸ. Pediatric Populations = 325
  Ⅹ. Special Studies = 325
   A. Animal Health Products = 325
   Suggested Reading = 326
 15. Use and Misuse of Statistics in the Design and Interpretation of Studies / Shayne C. Gad ; Colin G. Rousseaux
  Ⅰ. Introduction = 327
   A. Research and the Toxicologic Pathologist = 328
   B. Observations and Measurements = 331
  Ⅱ. Prerequisites to Statistical Analysis = 333
   A. Biological Variation = 333
   B. Describing Data = 335
   C. Biological and Statistical Significance = 340
  Ⅲ. Functions of Statistical Analyses = 344
   A. Hypothesis Testing and Probability (P) Values = 345
   B. Multiple Comparisons = 346
   C. Estimating the Size of the Effect = 346
  Ⅳ. An Overview of Experimental Design = 347
   A. Control = 347
   B. Bias and Change = 348
   C. Basic Principles of Experimental Design = 348
   D. Detecting Treatment Effects = 349
   E. Censoring = 353
   F. Impacts of Sample Size = 353
   G. Considerations Made before Designing the Experiment = 354
  Ⅴ. Designs Commonly Used in Toxicologic Studies = 355
   A. Completely Randomized Design = 355
   B. Completely Randomized Block Design = 356
   C. Latin Square Design = 356
   D. Factorial Design = 356
   E. Nested Design = 357
  Ⅵ. Managing Data = 357
   A. Bias = 357
   B. Bias and the Toxicologic Pathologist = 359
  Ⅶ. Statistical Methods = 360
   A. Statistical Analysis : General Considerations = 361
   B. Methods for Data Examination and Preparation = 370
   C. Exploratory Data Analysis = 376
   D. Hypothesis Testing of Categorical Data = 378
   E. Hypothesis Testing of Ordinal Data = 381
   F. Hypothesis Testing on Univariate Parameters = 385
   G. Hypothesis Testing on Multivariate Parameters = 390
   H. Modeling = 392
   I. Methods for the Reduction of Dimensionality = 399
   J. Meta-analysis = 404
   K. Bayesian Inference = 406
  Ⅷ. Data Analysis Application in Toxicologic Pathology = 408
   A. Body and Organ Weights = 409
   B. Clinical Chemistry = 411
   C. Hematology = 412
   D. Incidence of Histopathologic Findings = 412
   E. Carcinogenesis = 413
  Ⅸ. Summary and Conclusions = 414
   Suggested Reading = 415
 16. Preparation of the Report for a Toxicology／Pathology Study / Hugh E. Black
  Ⅰ. Introduction = 419
  Ⅱ. Clients = 419
  Ⅲ. Impact of a Poorly Written Report = 420
  Ⅳ. Preparation of the Final Report for a Toxicology Study = 421
  Ⅴ. Organization of the Report = 422
   A. Title Page = 422
   B. Information／Signature Page = 422
   C. Table of Contents = 423
   D. Quality Assurance Statement = 423
   E. Summary = 423
   F. Evaluation = 423
   G. Body of the Report = 424
   H. Things to Avoid in Preparing a Final Report = 431
  Ⅵ. Conclusion = 433
PART C : Selected Topics in Toxicologic Pathology
 17. Risk Assessment : The Changing Paradigm . Stephen K. Durham ; James A. Swenberg
  Ⅰ. Introduction = 437
  Ⅱ. Traditional Risk Assessment = 438
  Ⅲ. The Changing Paradigm = 440
  Ⅳ. Examples of Mechanistically Based Risk Assessment = 441
   A. $$α_2μ$$-Globulin Nephropathy = 441
   B. Peroxisome Proliferators = 442
   C. Butadiene = 442
  Ⅴ. Future Implications and Methodologies for Toxicology = 443
   Suggested Reading = 444
 18. Principles of Risk Communication : Building Trust and Credibility with the Public / Ronald W. Brecher ; Terry Flynn
  Ⅰ. Introduction = 447
  Ⅱ. The Risk Communication Perspective = 448
  Ⅲ. Risk Communication and Public Involvement = 448
  Ⅳ. Challenges and Obstacles to Effective Risk Communication = 449
   A. Data versus Information = 450
   B. The Public's Expectations of Science = 450
   C. Contradictory Expert Opinions = 450
  Ⅴ. Perception and Acceptance of Risk = 451
   A. Likelihood(Size) of the Adverse Effect = 451
   B. "Dread" Factor = 451
   C. permanent or Reversible Nature of the Adverse Effect = 451
   D. Voluntary Acceptance of Risks = 451
   E. Who Benefits from Acceptance of a Risk? = 451
   F. Jargon and Technical Terms = 451
   G. Age and Sex of the Risk Taker = 452
   H. Source of Information = 452
  Ⅵ. Assessing the Issue : "Is There a Risk?" = 451
   A. Problem Formulation = 452
   B. Exposure Assessment = 452
   C. Toxicity Assessment = 453
   D. Risk Characterization = 453
  Ⅶ. How Can Risks Be Managed? = 453
   A. How Do People Feel about the Risk? = 454
   B. Involving Stakeholders in Issue Definition = 455
  Ⅷ. Putting It All Together = 456
  Ⅸ. Summary = 456
   Suggested Reading = 456
 19. Biomedical Devices and Biomaterials / Mary E. P. Goad ; Dale L. Goad
  Ⅰ. Introduction = 459
  Ⅱ. Definition of Biomaterial and Biomedical Devices = 459
   A. Types of Biomaterials = 460
   B. Uses of Biomaterials = 461
  Ⅲ. Biomedical Devices = 461
   A. Soft Tissue Defects and Injury Repair = 461
   B. Bones and Joints = 462
   C. Heart Valves and Vessels = 469
   D. Silicone Implants = 470
   E. Bioengineered Implants and Delivery Systems = 471
  Ⅳ. Safety Evaluation of Biomaterials and Devices = 471
   A. Assessment of Lesions = 471
   B. Carcinogenicity = 474
   C. FDA and ISO Guidelines = 475
   Suggested Reading = 476
 20. Biotechnology and Its Products / Anne M. Ryan ; Timothy G. Terrell
  Ⅰ. Introduction = 479
  Ⅱ. Biopharmaceuticals = 480
   A. Biopharmaceuticals versus Small Molecule Therapeutics = 481
   B. Classes of Biopharmaceuticals = 481
   C. Recently Approved Biopharmaceuticals = 485
   D. Toxicologic Pathology Findings with Biopharmaceuticals = 488
  Ⅲ. Safety Evaluation of Biopharmaceuticals = 491
   A. Regulatory Resources = 491
   B. Study Design Issues = 492
   C. Other Studies = 494
  Ⅳ. Summary and Conclusions = 495
   Suggested Reading = 496
 21. Endocrine Disruptors / Paul S. Cooke ; Richard E. Peterson ; Rex A. Hess
  Ⅰ. Introduction = 501
  Ⅱ. Mechanisms of Endocrine Disruption = 502
  Ⅲ. Target Organs = 504
  Ⅳ. Classes of Compounds with Endocrine Disrupting Activity = 504
   A. Estrogens = 504
   B. Androgens and Antiandrogens = 511
   C. Effects of Endocrine Disruptors on Progesterone Signaling = 512
   D. Disruption of Endocrine Homeostasis through Other Steroid Receptors = 512
   E. Disruptors of Thyroid Hormone Homeostasis = 513
   F. Aryl Hydrocarbon Receptor(AhR) Agonists = 514
   G. Phytoestrogens = 516
  Ⅴ. Exposure to Endocrine Disruptors : Are There Risks? = 519
   A. Wildlife Populations = 519
   B. Human Health = 519
  Ⅵ. Techniques for Screening Endocrine Disruptors = 521
  Ⅶ. Conclusions, Controversy, and Questions = 522
   Suggested Reading = 523
 22. Radiation and Heat / Stephen A. Benjamin ; Barbara E. Powers ; Fletcher F. Hahn ; Donna F. Kusewitt
  Ⅰ. Introduction = 529
   A. Sources and Occurrence = 530
  Ⅱ. Ionizing Radiation = 532
   A. Nature and Action of Ionizing Radiation = 532
   B. Mechanisms of Ionizing Radiation Injury = 536
   C. Response to Injury Induced by Ionizing Radiation = 545
  Ⅲ. Ultraviolet Radiation = 579
   A. Nature and Action of Ultraviolet Radiation = 579
   B. Mechanisms of Ultraviolet Radiation Injury = 579
   C. Response to Injury Induced by Ultraviolet Radiation = 581
  Ⅳ. Hyperthermia = 589
   A. Clinical Use of Hyperthermia = 589
   B. Mechanisms of Hyperthermia-Induced Injury = 589
   C. Response to Injury Induced by Hyperthermis = 590
   Suggested Reading = 592
 23. Nutritional Toxicologic Pathology / Elizabeth H. Jeffery ; Matthew A. Wallig ; M. E. Tumbleson
  Ⅰ. Introduction = 595
  Ⅱ. Macronutrients = 597
   A. Proteins = 597
   B. Carbohydrates = 600
   C. Fats = 601
   D. Fiber = 602
  Ⅲ. Micronutrients = 603
   A. Vitamins = 603
   B. Minerals = 614
  Ⅳ. Dietary Contaminants = 627
   Suggested Reading = 629
 24. Phycotoxins / Philip F. Solter ; Val R. Beasley
  Ⅰ. Introduction = 631
  Ⅱ. Diarrheic Shellfish Poisoning = 631
  Ⅲ. Paralytic Shellfish Poisoning = 633
  Ⅳ. Amnesic Shellfish Poisoning = 634
  Ⅴ. Ciguatera Fish Poisoning = 635
  Ⅵ. Pfiesteria Toxicoses = 636
  Ⅶ. Cyanbacterial Toxins = 636
   A. Neurotoxins = 636
   B. Hepatotoxins = 637
   Suggested Reading = 641
 25. Selected Mycotoxins Affecting Animal and Human Health / Wanda M. Haschek ; Kenneth A. Voss ; Val R. Beasley
  Ⅰ. Introduction = 645
  Ⅱ. Aflatoxins = 650
   A. Source／Occurrence = 650
   B. Toxicology = 651
   C. Clinical Signs and Pathology = 653
   D. Human Risk = 655
   E. Diagnosis, Treatment, and Control = 656
  Ⅲ. Ochratoxins = 656
   A. Source／Occurrence = 656
   B. Toxicology = 657
   C. Clinical Signs and Pathology = 658
   D. Human Risk = 659
   E. Diagnosis, Treatment, and Prevention = 662
  Ⅳ. Trichothecene Mycotoxins = 662
   A. Sources／Occurrence = 662
   B. Toxicology = 662
   C. Clinical Signs and Pathology = 664
   D. Human Risk = 668
   E. Diagnosis, Treatment, and Prevention = 670
  Ⅴ. Zearalenone = 670
   A. Sources／Occurrence = 670
   B. Toxicology = 670
   C. Clinical Signs and Pathology = 671
   D. Human Risk = 672
   E. Diagnosis, Treatment, and Prevention = 672
  Ⅵ. Fumonisins = 672
   A. Sources／Occurrence = 672
   B. Toxicology = 673
   C. Clinical Signs and Pathology = 676
   D. Human Risk = 682
   E. Diagnosis, Treatment, and Prevention = 683
  Ⅶ. Ergot Alkaloids = 683
   A. Sources／Occurrence = 683
   B. Toxicology = 684
   C. Clinical Signs and Pathology = 687
   D. Human Risk = 689
   E. Diagnosis, Treatment, and Prevention = 690
  Ⅷ. Summary／Conclusion = 690
   Suggested Reading = 691
 26. Heavy Metals / Sharon M. Gwaltney-Brant
  Ⅰ. Introduction = 701
  Ⅱ. Cadmium = 701
   A. Sources and Exposure = 701
   B. Kinetics = 702
   C. Mechanism of Action = 703
   D. Acute Toxicity = 704
   E. Chronic Toxicity = 704
   F. Carcinogenicity = 706
  Ⅲ. Mercury = 707
   A. Sources and Exposure = 707
   B. General Mechanism of Action = 707
   C. Elemental Mercury = 708
   D. Inorganic Mercury = 709
   E. Organic Mercury = 710
   F. Carcinogenicity = 711
  Ⅳ. Lead = 712
   A. Sources and Exposure = 712
   B. Kinetics = 712
   C. Mechanism of Action = 713
   D. Acute Toxicity = 714
   E. Chronic Toxicity = 715
   F. Carcinogenicity = 716
  Ⅴ. Arsenic = 716
   A. Chemical Forms = 716
   B. Inorganic Arsenic = 717
   C. Phenylarsonics = 720
   D. Arsine = 720
  Ⅵ. Uranium and Plutonium = 721
   A. Uranium = 721
   B. Plutonium = 722
  Ⅶ. Thallium = 723
   A. Sources and Exposure = 723
   B. Kinetics = 723
   C. Mechanism of Action = 723
   D. Toxicity = 723
   E. Carcinogenicity = 725
  Ⅷ. Bismuth = 725
   A. Sources and Exposure = 725
   B. Kinetics = 725
   C. Mechanism of Action = 725
   D. Toxicity = 725
   E. Teratogenicity and Carcinogenicity = 726
  Ⅸ. Antimony = 726
   A. Sources and Exposure = 726
   B. Kinetics and Mechanism of Action = 726
   C. Toxicity = 727
   D. Carcinogenicity = 727
  Ⅹ. Beryllium = 727
   A. Sources and Exposure = 727
   B. Kinetics = 728
   C. Acute Toxicity = 728
   D. Chronic Toxicity = 728
   E. Carcinogenicity = 730
  XI. Summary and Conclusions = 730
   Suggested Reading = 730
[Volume. 2]----------
CONTENTS
VOLUME 2 Organ-Specific Toxicologic Pathology
 27. Organ-Specific Toxicologic Pathology : An Introduction / Colin G. Rousseaux ; Wanda M. Haschek ; Matthew A. Wallig = 1
 28. Respiratory System / Wanda M. Haschek ; Hanspeter R. Witschi ; Kristen J. Nikula
  Ⅰ. Introduction = 3
  Ⅱ. Structure and Cell Biology = 4
   A. Macroscopic and Microscopic Anatomy = 4
   B. Physiology and Functional Considerations = 19
   C. Xenobiotic Exposure, Metabolism, and Excretion = 24
  Ⅲ. Mechanisms of Toxicity = 29
   A. Direct Toxicity = 30
   B. Metabolic Activation = 31
   C. Immune-Mediated Toxicity = 33
   D. Toxicity and Responses to Inhaled Particles = 34
   E. Xenobiotic Interactions = 35
   F. Modifying Factors in Toxicity = 36
  Ⅴ. Response to Injury = 36
   A. Injury, Regeneration, and Repair = 37
   B. Nasopharyngeal and Laryngeal Responses to Injury = 39
   C. Airway Response to Injury = 46
   D. Pulmonary Parenchymal Response to Injury = 51
  Ⅵ. Testing for Toxicity = 68
   A. Methods for Testing = 69
   B. Evaluation of Toxicity = 72
   C. Animal Models = 78
   Suggested Reading = 79
 29. Skin and Oral Mucosa / Andres J. P. Klein-Szanto ; Claudio J. Conti
  Ⅰ. Skin = 85
   A. Introduction = 85
   B. Structure and Function of Skin = 85
   C. Mechanisms of Cutaneous Toxicity = 94
   D. Response of Skin to Injury = 98
   E. Evaluation of Cutaneous Toxicity = 109
  Ⅱ. Oral Mucosa = 112
   A. Introduction = 112
   B. Structure and Function of Oral Mucosa = 112
   C. Mechanisms of Mucosal Toxicity = 113
   D. Response of Oral Mucosa to Injury = 113
   E. Evaluation of Oral Toxicity = 115
   Suggested Reading. = 116
 30. Gastrointestinal Tract / T. A. Bertram
  Ⅰ. Introduction = 121
  Ⅱ. Structure and Function of the Gastrointestinal Tract = 122
   A. Macroscopic and Microscopic Structure and Function = 122
   B. Enteric Lymphoid System = 133
   C. Enteric Nervous System = 135
   D. Biotransformation = 137
   E. Bacterial Metabolism = 140
   F. Enterohepatic Circulation = 141
  Ⅲ. Mechanisms of Gastrointestinal Toxicity = 143
   A. Intestinal Barrier Function = 143
   B. Intestinal Malabsorption = 144
   C. Hypoxia = 145
   D. Mucosal Barrier Damage and Cytotoxicity = 146
   E. Hypersensitivity = 150
   F. Acetylcholinesterase Inhibitors = 151
   G. Perturbation of Enteric Microflora = 151
   H. Carcinogenicity = 152
  Ⅳ. Response of Gastrointestinal Tract to Injury = 155
   A. Pathophysiological Response = 155
   B. Inflammatory Response = 158
   C. Mucosal Response = 158
   D. Organ-Specific Response = 164
  Ⅴ. Evaluation of Gastrointestinal Toxicity = 169
   A. In vitro Strategies = 169
   B. In Vivo Strategies = 170
   C. Molecular Pathology = 170
   D. Morphological Methods = 171
   E. Animal Models = 178
   Suggested Reading = 184
 31. Liver / Russell C. Cattley ; James A. Popp
  Ⅰ. Introduction = 187
  Ⅱ. Structure and Function = 187
   A. Gross Anatomy = 188
   B. Cell Components = 188
   C. Xenobiotic Metabolism = 190
  Ⅲ. Cellular Mechanisms of Toxicity = 190
  Ⅳ. Nonneoplastic Responses to Injury = 190
   A. Histologic Types of Hepatic Necrosis = 192
   B. Hepatic Lipidosis = 198
   C. Infiltration and Pigments = 199
   D. Pathology of Transcription and Translation = 200
   E. Cholestasis = 202
   F. Hepatocellular Adaptive Responses = 202
   G. Hepatocellular Proliferation = 204
   H. Bile Ductular Lesions = 205
   I. Nonparenchymal Cell Toxicity = 209
   J. Hepatitis = 211
   K. Cirrhosis = 211
  Ⅴ. Hepatic Neoplasia = 212
   A. Hepatocellular Neoplasia = 212
   B. Bile Duct Neoplasms = 215
   C. Endothelial Neoplasms = 217
   D. Kupffer Cell Neoplasms = 218
  Ⅵ. Testing for Toxicity = 218
   A. Whole Animal = 218
   B. Perfused Liver Preparations = 221
   C. Cultured Hepatocytes = 221
   D. Liver Slices = 221
   E. Use of Animals as Models = 222
  Ⅶ. Summary and Conclusions = 222
   Suggested Reading = 222
 32. Pancreas / Daniel S. Longnecker ; Glenn L. Wilson
  Ⅰ. Overview = 227
  Ⅱ. Exocrine Pancreas = 227
   A. Introduction = 227
   B. Normal Structure of the Exocrine Pancreas = 227
   C. Physiology of the Exocrine Pancreas = 230
   D. Mechanisms of Toxicity in Exocrine Pancreas = 230
   E. Response of the Exocrine Pancreas to Injury = 231
   F. Evaluation of Exocrine Pancreatic Toxicity = 237
   G. Summary and Conclusions = 241
  Ⅲ. Endocrine Pancreas = 241
   A. Structure of Endocrine Pancreas = 241
   B. Physiology of Endocrine Pancreas = 243
   C. Mechanisms of Endocrine Pancreatic Toxicity = 244
   D. Response to Injury = 248
   E. Evaluation of Endocrine Pancreatic Toxicity = 251
   F. Summary and Conclusions = 252
   Suggested Reading = 252
 33. Kidney / Kanwar Nasir M. Khan ; Carl L. Alden
  Ⅰ. Introduction = 255
  Ⅱ. Renal Structure and Function = 256
   A. Gross, Microscopic, and Ultrastructural Anatomy = 256
   B. Physiology = 265
  Ⅲ. Molecular Pathology of the Kidney = 271
   A. Growth Factors, Protooncogenes, Chemokines, and Heat Shock Proteins = 271
   B. Molecular Targets of Emerging Novel Therapeutics = 272
   C. Genetically Modified Rodent Models = 277
  Ⅳ. Mechanisms of Toxicity = 278
   A. Overview and Classification = 278
   B. Glomerular Injury = 280
   C. Proximal Tubular Injury = 285
   D. Other Sites of Injury = 302
   E. Renal Carcinogenesis = 305
  Ⅴ. Response to Injury = 312
   A. Introduction = 312
   B. Glomerulus = 314
   C. Proximal Tubule = 315
   D. Renal Papilla = 318
   E. Tubular Hyperplasia and Neoplasia = 318
   F. Predictors of Carcinogenesis = 322
  Ⅵ. Testing for Kidney Toxicity = 323
   A. Routine Screening of New Chemicals = 323
   B. Methodology for Refinement of the Risk Assessment = 324
   C. Spontaneous Renal Disease = 327
  Ⅶ. Conclusion = 329
   Suggested Reading = 330
 34. Lower Urinary Tract / Samuel M. Cohen ; Hideaki Wanibuchi ; Shoji Fukushima
  Ⅰ. Introduction = 337
  Ⅱ. Structure and Function = 337
   A. Kidney Pelvis = 337
   B. Ureters = 338
   C. Urinary Bladder = 338
   D. Urethra = 338
   E. Urothelium = 339
  Ⅲ. Mechanisms of Toxicity = 340
   A. Urinary Chemistry = 340
   B. Urinary Solids = 341
   C. Chronic Injury = 344
   D. Carcinogenesis = 344
  Ⅳ. Response to Injury = 346
   A. Nonneoplastic Lesions = 346
   B. Epithelial Neoplasms = 350
   C. Urothelial Carcinoma = 350
   D. Mesenchymal Tumors = 352
  Ⅴ. Testing for Toxicity = 352
   A. Evaluation of Urine = 352
   B. Morphologic Evaluations = 356
   C. Animal Models = 358
   Suggested Reading = 359
 35. Cardiovascular and Skeletal Muscle Systems / John F. Van Vleet ; Victor J. Ferrans ; Eugene Herman
  Ⅰ. Heart = 363
   A. Introduction = 363
   B. Structure and Function = 363
   C. Mechanisms of Toxicity = 373
   D. Response to Injury = 382
   E. Testing for Toxicity = 400
  Ⅱ. Vessels = 410
   A. Introduction = 410
   B. Structure and Function = 410
   C. Mechanisms of Toxicity = 415
   D. Response to Injury = 419
   E. Evaluation of Vasotoxic Effects = 425
  Ⅲ. Skeletal Muscle = 429
   A. Introduction = 429
   B. Structure and Function = 430
   C. Mechanisms of Toxicity = 433
   D. Response to Injury = 435
   E. Evaluation of the Effects of Xenobiotics on Skeletal Muscle = 439
   Suggested Reading = 446
 36. Bones and Joints / J. C. Woodard ; J. E. Burkhardt ; T. Lee ; W. Lee
  Ⅰ. Introduction = 457
  Ⅱ. Skeletal Structure and Composition = 457
   A. Formation and Development = 457
   B. Blood Supply and Nerves = 460
   C. Composition of Bone = 460
   D. Species Differences in Composition and Changes with Age = 461
  Ⅲ. Bone Physiology and Function = 461
   A. Modeling and Remodeling of Bone = 461
   B. Biomechanics = 462
   C. Mineral Homeostasis = 462
   D. Regulation of Bone Cell Function = 463
  Ⅳ. Mechanisms of Toxicity = 466
   A. Bone Toxicity = 466
   B. Joint Toxicity = 475
  Ⅴ. Response of the Skeleton to Toxic Injury = 476
   A. Bone = 476
   B. Joints = 489
  Ⅵ. Evaluation of Skeletal Toxicity = 494
   A. Testing for Skeletal Toxicity = 494
   B. Morphologic Evaluation = 495
   C. Biochemical Evaluation = 501
   D. Animal Models of Skeletal Disease = 502
  Ⅶ. Summary = 503
   Suggested Reading = 503
 37. Nervous System / David C. Dorman ; Karrie A. Brenneman ; Brad Bolon
  Ⅰ. Introduction = 509
  Ⅱ. Structure and Function of the Nervous System = 510
   A. Macroscopic Structure = 510
   B. Microscopic Anatomy = 511
   C. Specialized Anatomical Features = 512
   D. Select Functions = 513
  Ⅲ. Mechanisms of Disease and Classification of Neurotoxic Diseases = 517
   A. Neuronopathies = 518
   B. Axonopathies = 521
   C. Myelinopathies = 523
   D. Toxicants Affecting Vascular Integrity = 525
   E. Developmental Neurotoxicants = 525
   F. Neurocarcinogens = 527
  Ⅳ. Testing for Neurotoxicity = 528
   A. Animal Testing = 528
   B. Use of in Vitro Systems in Neurotoxicity Testing = 534
  Ⅴ. Conclusions = 535
   Suggested Reading = 535
 38. The Eye / Herbert E. Whiteley ; Robert L. Peiffer
  Ⅰ. Introduction = 539
  Ⅱ. Development of the Eye = 540
   A. Structure, Function, and Cell Biology = 540
   B. Mechanisms of Toxicity = 540
  Ⅲ. Cornea = 542
   A. Structure, Function, and Cell Biology = 542
   B. Mechanisms of Toxicity = 549
  Ⅳ. Lens = 553
   A. Structure and Function = 554
   B. Mechanisms of Toxicity = 555
  Ⅴ. Retina and Retinal Pigment Epithelium = 557
   A. Structure and Function = 557
   B. Mechanisms of Toxicity = 561
   C. Summary = 570
  Ⅵ. Toxicologic, Clinical, and Pathologic Evaluation = 571
   A. Animal Models : Which Ones? = 571
   B. Clinical Ophthalmic Examination = 571
   C. Other Clinical Diagnostic Techniques = 572
   D. Morphologic Evaluation = 573
  Ⅶ. Ocular Toxicity Testing = 574
   A. Ocular Irritation : Draize Test = 574
   B. Alternative to the Draize Test = 576
   C. Models of Retinal Toxicity = 577
   D. Other in Vitro Models = 577
  Ⅷ. Conclusions = 577
   Suggested Reading = 578
 39. Immune System / C. Frieke Kuper ; Emile de Heer ; Henk Van Loveren ; Joseph G. Vos
  Ⅰ. Introduction = 585
  Ⅱ. Structure and Function of the Immune System = 585
   A. Function of the Immune System = 585
   B. Structure of the Immune System = 592
  Ⅲ. Mechanisms of Immune Toxicity = 604
   A. Introduction = 604
   B. Examples of Immunotoxic Agents = 607
   C. Immune Derangements and Neoplasia = 620
  Ⅳ. Response of Lymphoid Tissue to Toxic Injury = 621
   A. Decreased Cellularity, Depletion, Atrophy, and Involution = 622
   B. Increased Cellularity, Hyperplasia, Germinal Center Development, and Macrophage Accumulations = 632
   C. Neoplasia = 635
  Ⅴ. Inflammation in Nonlymphoid Organs : Autoimmune Disease and Allergy = 635
  Ⅵ. Testing for Immunotoxicity = 641
   A. Introduction = 641
   B. Animal Models = 643
  Ⅶ. Summary = 643
   Suggested Reading = 644
 40. Hematopoietic System / V. E. Valli ; J. P. McGrath ; I. Chu
  Ⅰ. Introduction = 647
  Ⅱ. Phylogeny and Ontogeny of the Hematopoietic and Lymphoid Systems = 647
  Ⅲ. Structure and Function = 648
   A. Gross and Microscopic Anatomy = 648
   B. Hematopoiesis = 655
   C. Cellular Kinetics = 660
  Ⅳ. Hematopoietic Assessment = 662
  Ⅴ. Interpreting Changes in Blood and Hematopoietic Tissues = 663
   A. Maturation Index of Myeloproliferation = 666
  Ⅵ. Hematotoxic Agents and Mechanisms = 672
  Ⅶ. Summary and Future Direction = 677
   Suggested Reading = 677
 41. Endocrine System / Charles C. Capen ; Ronald A. DeLellis ; John T. Yarrington
  Ⅰ. Introduction = 681
  Ⅱ. Adrenal Cortex = 681
   A. Structure and Function = 681
   B. Mechanisms of Toxicity = 686
   C. Response to Injury = 687
   D. Testing for Toxicity = 697
   E. Use of Animals as Models = 699
  Ⅲ. Adrenal Medulla
   A. Structure and Function = 699
   B. Mechanisms of Toxicity = 700
   C. Response to Injury = 701
   D. Testing for Toxicity = 706
  Ⅳ. Pituitary Gland = 706
   A. Structure and Function = 706
   B. Mechanisms of Toxicity = 710
   C. Response to Injury = 713
   D. Testing for Toxicity = 718
  Ⅴ. Thyroid C Cells
   A. Structure and Function = 719
   B. Mechanisms of Toxicity = 721
   C. Response to Injury = 721
  Ⅵ. Thyroid Follicular Cells = 725
   A. Structure and Function = 725
   B. Mechanisms of Toxicity = 732
   C. Response to Injury = 743
   D. Evaluation of Toxicity = 750
  Ⅶ. Parathyroid Gland = 755
   A. Introduction = 755
   B. Structure and Function = 755
   C. Mechanisms of Toxicity = 760
   D. Response of Parathyroid Chief Cells to Injury = 765
   E. Evaluation of Toxicity = 770
   Suggested Reading = 771
 42. Male Reproductive System / Dianne M. Creasy ; Paul M. D. Foster
  Ⅰ. Introduction = 785
  Ⅱ. Structure and Cell Biology = 785
   A. Embryological Derivation of the Reproductive Tract = 785
   B. Development of the Reproductive Tract = 786
   C. Structure of the Testes = 787
   D. Physiology and Functional Consideration of the Testes = 792
   E. Structure and Function of the Epididymis and Excurrent Ducts = 805
   F. Structure and Function of Accessory Sex Organs = 806
   G. Penis and Ejaculation = 807
  Ⅲ. Mechanisms of Toxicity = 808
   A. Role of Metabolism = 809
   B. Cell-Specific Toxicity in the Testes = 810
   C. Vascular Effects and Indirect Toxicity to the Testes = 816
   D. Epididymal and Sperm Toxicity = 817
   E. Secondary Sex Organs = 818
   F. Hormone Disruption = 818
   G. Toxicity to the Developing Male Reproductive Tract = 820
  Ⅳ. Responses to Injury = 822
   A. Disruption of Spermatogenesis = 822
   B. Tubular Dilatation and Tubular Shrinkage = 828
   C. Tubular and Testicular Necrosis = 828
   D. Leydig Cell Response = 828
   E. Disruption of Sperm Maturation = 830
   F. Epididymal Response = 830
   G. Response to Alterations in Hormone Balance = 831
   H. Reversibility = 836
  Ⅴ. Testing for Toxicity = 837
   A. Detecting Toxicity = 837
   B. Characterization of Male Reproductive Toxicity = 838
   C. Functional Characterization = 841
   D. Testing for Toxicity of the Developing Male Reproductive Tract = 843
  Ⅵ. Conclusions = 844
   Suggested Reading = 844
 43. Female Reproductive System / Yang-Dar Yuan ; George L. Foley
  Ⅰ. Introduction = 847
  Ⅱ. Structure and Functional Physiology = 848
   A. Structure = 848
   B. Functional Physiology = 859
  Ⅲ. Mechanisms of Toxicity = 865
   A. General Toxicity : Ovary, Uterus, and Vaginal as a Unit = 865
   B. Local Vaginal Toxicity = 870
   C. Carcinogenesis = 871
  Ⅳ. Response to Injury = 872
   A. General Responses : Ovary, Uterus, and Vagina as a Unit = 872
   B. Local Inflammation of Vagina = 878
   C. Neoplasia = 880
  Ⅴ. Testing for Toxicity = 886
   A. General Toxicity = 886
   B. Local Vaginal Toxicity = 888
  Ⅵ. Summary = 889
   Suggested Reading = 889
 44. Embryo and Fetus / Ronald D. Hood ; Colin G. Rousseaux ; Patricia M. Blakley
  Ⅰ. Introduction = 895
   A. Overview of Fetal Toxicologic Pathology = 895
   B. Basic Principles of Developmental Toxicology = 895
   C. Incidence of Congenital Anomalies = 896
  Ⅱ. Normal Morphologic Development = 896
   A. Fertilization and Blastocyst Formation = 897
   B. Gastrulation = 897
   C. Organogenesis = 897
   D. Histogenesis and Functional Maturation = 900
  Ⅲ. Mechanisms of Toxicity = 901
   A. Critical Phase of Intrauterine Development = 901
   B. Modifying Factors = 902
  Ⅳ. Response to Injury = 906
   A. Death = 906
   B. Malformations = 907
   C. Intrauterine Growth Retardation = 910
   D. Perinatal Toxicology = 911
   E. Endocrine Disruption = 912
   F. Congenital Neoplasia = 912
   G. How Dose Relates to Manifestation of Abnormal Development = 914
  Ⅴ. Selected Malformations = 914
   A. Central Nervous System = 914
   B. Craniofacial Structures = 920
   C. Cardiovascular System = 922
   D. Respiratory System = 923
   E. Gastrointestinal System = 924
   F. Urinary System = 924
   G. Reproductive System = 925
   H. Skeletal System = 925
  Ⅵ. Developmental Toxicity Testing and Risk Assessment = 927
   A. Hazard Identification and Dose-Response Analysis = 927
   B. Dose-Response Evaluation = 932
   C. Risk Characterization = 933
   D. Conclusions = 933
   Suggested Reading = 933
Index = 937