Handbook of Toxicologic Pathology (eBook)

Front Cover 1
Handbook of Toxicologic Pathology 4
Copyright Page 5
Table of Contents 8
Dedication 6
Contributors 20
Preface 24
Chapter 1. Toxicologic Pathology: An Introduction 26
I. The Problem 26
II. An Experimental Approach 29
III. Role of the Toxicologic Pathologist 29
IV. The Future 31
SUGGESTED READING 32
Chapter 2. The Pathologist in Toxicologic Testing and Evaluation 34
I. Introduction 34
II. Types of Studies, Experimental Design, and Evaluation 37
III. Evaluation of Injury 40
IV. Summary 45
ACKNOWLEDGMENT 45
SUGGESTED READING 45
Chapter 3. Evaluation of Altered Morphology 48
I. Introduction 48
II. Factors Influencing the Evaluation of Altered Morphology 49
III. Summary 58
ACKNOWLEDGMENT 58
SUGGESTED READING 58
Chapter 4. Quantitative Techniques for Morphological Evaluation 62
I. Introduction 62
II. Morphometry 62
III. Cytokinetics 65
IV. Flow Cytometry 69
SUGGESTED READING 73
Chapter 5. Biochemical Basis of Toxicity 74
I. Introduction 75
II. Absorption 76
III. Distribution 77
IV. Biotransformation 79
V. Excretion 82
VI. Factors Causing Variation in Handling of Toxic Compounds 85
VII. Interaction of Agent 
87 
VIII. Site-Specific Interactions 89
IX. Nonspecific Interaction 91
X. Mechanisms of Protection 93
SUGGESTED READING 95
Chapter 6. Biochemical Mechanisms of Toxic Cell Injury 96
I. Introduction 96
II. Reaction of Cells to Chemicals and Other Stresses 97
III. Role of Metabolism in Toxic Cell Injury 100
IV. Covalent Binding Hypothesis of Cell Injury 104
V. OXYGEN RADICALS AS MEDIATORS OF TOXIC CELL INJURY 106
VI. Biochemical Mechanisms of Cell Injury 110
VII. Summary 114
SUGGESTED READING 114
Chapter 7. Chemical Carcinogenesis 116
I. Nomenclature of Neoplasms 117
II. Spectrum of Proliferative Lesions 118
III. Steps in the Neoplastic Process 124
IV. Hypotheses of Mode of Action of Chemical Carcinogens 130
V. Oncogenes and Tumor Suppressor Genes in Chemical Carcinogenesis 138
VI. Tests for Carcinogenic Potential of Chemicals 144
VII. Conclusion 150
SUGGESTED READING 150
GLOSSARY 152
Chapter 8. The Limitations of Toxicologic Pathology 156
I. Introduction 156
II. Relationship of Structural Alteration to Altered Function 157
III. Temporal–Spatial Problems 164
IV. Integrative Toxicology and Pathology 165
V. Summary 166
ACKNOWLEDGMENT 167
SUGGESTED READING 167
Chapter 9. Regulatory Aspects and Potential Pitfalls of Toxicologic Pathology 168
I. Regulatory Agencies 168
II. Good Laboratory Practice Regulations 171
III. Standard Operating Procedures 173
IV. Quality Assurance 175
V. Data Handling and Report Writing 176
VI. Summary 177
ACKNOWLEDGMENT 178
SUGGESTED READING 178
Chapter 10. Risk Assessment 180
I. Introduction 180
II. Risk Assessment: The Process 183
SUGGESTED READING 188
Chapter 11. Skin and Oral Mucosa 190
PART I. SKIN 190
Part II. ORAL MUCOSA 213
SUGGESTED READING 216
Chapter 12. Gastrointestinal Tract 220
I. Introduction 220
II. Structure and Function of Gastrointestinal Tract 221
III. Mechanisms of Gastrointestinal Toxicity 239
IV. Response of Gastrointestinal Tract to Injury 248
V. Evaluation of Gastrointestinal Toxicity 263
ACKNOWLEDGMENTS 273
SUGGESTED READING 273
Chapter 13. Pancreas 278
PART I. EXOCRINE PANCREAS 279
PART II. ENDOCRINE PANCREAS 292
SUGGESTED READING 302
Chapter 14. Hepatobiliary System 304
I. Introduction 304
II. Structure and Function 305
III. Cellular Mechanisms of Toxicity 308
IV. Nonneoplastic Responses to Injury 308
V. Hepatic Neoplasia 327
VI. Testing for Toxicity 333
VII. Summary and Conclusions 336
ACKNOWLEDGMENTS 337
SUGGESTED READING 337
Chapter 15. Urinary System 340
PART I. KIDNEY 341
PART II. UROTHELIUM 392
ACKNOWLEDGMENTS 404
SUGGESTED READING 404
Chapter 16. Blood and Bone Marrow 414
I. Introduction 414
II. Structure and Cell Biology 415
III. Mechanisms of Toxicity 424
IV. Response to Injury 426
V. Evaluation of Bone Marrow Toxicity 436
VI. Summary and Conclusions 438
SUGGESTED READING 439
Chapter 17. Immune System 446
I. Introduction 446
II. Function and Structure of the Immune System 447
III. Mechanisms of Toxicity and Response to Injury 466
IV. Morphology of the Response to Toxic Injury 482
V. Testing for Immunotoxicity 502
VI. Summary 507
SUGGESTED READING 508
Chapter 18. Skeletal System 514
I. Introduction 514
II. Skeletal Structure and Composition 515
III. Bone Physiology and Function 519
IV. Mechanisms of Toxicity 523
V. Response of the Skeleton to Toxic Injury 532
VI. Evaluation of Skeletal Toxicity 550
VII. Summary 558
SUGGESTED READING 559
Chapter 19. Cardiovascular and Skeletal Muscle Systems 564
HEART 565
VESSELS 608
SKELETAL MUSCLE 627
SUGGESTED READING 643
Chapter 20. Nervous System 650
I. Introduction 650
II. Structure and Function 651
III. Mechanisms of Toxicity 658
IV. Response to Injury 663
V. Testing for Toxicity 692
VI. Use of Animals as Models for Human Neurotoxicity 695
VII. Conclusions 695
SUGGESTED READING 696
Chapter 21. Endocrine System 700
I. Introduction 700
II. Adrenal Cortex 701
III. Adrenal Medulla 717
IV. Pituitary Gland 722
V. Thyroid C Cells 730
VI. Thyroid Follicular Cells 736
VII. Parathyroid Gland 761
SUGGESTED READING 776
Chapter 22. Respiratory System 786
I. Introduction 786
II. Structure and Cell Biology 787
III. Mechanisms of Toxicity 811
IV. Response to Injury 816
V. Testing for Toxicity 839
SUGGESTED READING 848
Chapter 23. Male Reproductive System 854
I. Introduction 854
II. Structure and Cell Biology 855
III. Physiology and Functional Considerations 879
IV. Mechanisms of Toxicity 885
V. Response to Injury 891
VI. Testing for Toxicity 902
VII. Conclusions 912
SUGGESTED READING 912
Chapter 24. Female Reproductive System 916
I. Introduction 916
II. Structure and Functional Physiology 917
III. Mechanisms of Toxicity 932
IV. Response to Injury 939
V. Testing for Toxicity 954
VI. Summary 956
ACKNOWLEDGMENTS 956
SUGGESTED READING 956
Chapter 25. Fetus 962
I. Introduction 963
II. Normal Morphologic Development 964
III. Mechanisms of Toxicity 968
IV. Response to Injury 974
V. Selected Malformations 983
VI. Teratogenicity Testing and Risk Assessment 996
VII. Conclusions 1000
SUGGESTED READING 1001
GLOSSARY 1004
Chapter 26. Radiation and Heat 1008
Introduction 1009
PART I. IONIZING RADIATION 1012
PART II. ULTRAVIOLET RADIATION 1055
PART III. HYPERTHERMIA 1064
SUGGESTED READING 1068
Index 1072