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Index
Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Preface
VOLUME 1: General Toxicologic Pathology
PART A: Basics of Toxicologic Pathology
Chapter 1: Toxicologic Pathology: An Introduction
I. An Overview of Toxicologic Pathology
II. The Need for Toxicologic Pathology in Modern Society
III. The Future of Toxicologic Pathology
IV. Summary
Chapter 2: Biochemical Basis of Toxicity
I. Introduction
II. Absorption
III. Distribution
IV. Biotransformation
V. Excretion
VI. Factors Causing Variation in Handling of Toxic Compounds
VII. Interaction of Agent and Organism
VIII. Site-Specific Interactions
IX. Nonspecific Interaction
X. Mechanisms of Protection
Chapter 3: Morphologic Manifestations of Toxic Cell Injury
I. Introduction
II. Reversible Cell Injury
III. Irreversible Cell Injury
IV. Concluding Comments
Chapter 4: Organelle Biochemistry and Regulation of Cell Death
I. Overview and Nomenclature
II. Cell Membrane
III. Cytoskeleton
IV. Mitochondrion
V. Endoplasmic Reticulum
VI. Nucleus
VII. Extracellular Matrix
VIII. Summary
Chapter 5: Carcinogenesis
I. Introduction
II. The Spectrum of Proliferative Lesions
III. Steps in the Neoplastic Process
IV. Hypotheses of Mode of Action of Chemical Carcinogens
V. Oncogenes and Tumor Suppressor Genes in Chemical Carcinogenesis
VI. Cell Cycle Control and Carcinogenesis
VII. Tests for Carcinogenic Potential of Chemicals
Chapter 6: Applied Clinical Pathology in Preclinical Toxicology Testing
I. Introduction
II. Hematology
III. Clinical Chemistry
IV. Microsomal Enzyme Induction
V. Urinalysis
VI. Clinical Pathology Study Design Considerations
VII. Clinical Pathology Result Interpretation
VIII. Reporting of Clinical Pathology Findings
IX. Overall Result Reporting
X. Summary
Chapter 7: Nomenclature
I. Introduction
II. Terminology Issues
III. Suggested Practices
IV. Summary
PART B: The Practice of Toxicologic Pathology
Chapter 8: Basic Techniques
I. Introduction
II. Factors Influencing the Evaluation of Altered Morphology
III. Summary
Chapter 9: Managing Pitfalls in Toxicologic Pathology
I. Introduction
II. Study Design
III. Necropsy
IV. Histology
V. Computer Systems
VI. Peer Review
VII. Conclusions
Chapter 10: Special Techniques in Toxicologic Pathology
I. Introduction
II. Immunohistochemistry in Toxicologic Pathology
III. In Situ Hybridization
IV. Flow Cytometry
V. In Situ Polymerase Chain Reaction (PCR)/in Situ Reverse Transcriptase-PCR
VI. Laser Capture Microdissection
VII. Confocal Microscopy
VIII. Stereology
Chapter 11: Application of New Technologies to Toxicologic Pathology
I. Introduction
II. Genomics: High-Density Nucleic Acid Microarrays
III. Proteomics
IV. Metabonomics: Pattern Recognition Nuclear Magnetic Resonance Spectroscopy
V. Laser Capture Microscopy
VI. Computational Modeling
VII. Summary
Chapter 12: Issues in Laboratory Animal Science for the Toxicologic Pathologist
I. Introduction
II. Regulatory Issues
III. Selection of Animal Models
IV. Animal Health Considerations
V. Housing and Husbandry Issues
VI. The Role of Diet in Toxicology Studies
VII. Summary
Chapter 13: New Animal Models in Toxicology
I. Many Strains of Genetically Engineered Rodents Are Available for Use in Toxicology
II. Genetically Engineered Mice Can Be Used for in Vivo Genetic Toxicity Testing
III. Genetically Engineered Mice Can Be Used to Study Mechanisms of Toxicity in Vivo
IV. Genetically Modified Mice Can Be Used for Special or Customized Toxicity Testing
V. Genetically Engineered Mice Can Be Useful for Short-Term Carcinogenicity Testing
VI. Caveats Apply to the Use of Genetically Engineered Mice in Research
VII. New Gene-Altering Technologies Will Produce More Sophisticated Mouse Models
Chapter 14: Pathology Issues in the Design of Toxicology Studies
I. Introduction
II. Landmarks in Compound Development
III. Role of the Pathologist in Compound Development
IV. Regulatory Studies
V. General Considerations for the Use of Pathology in Regulatory Studies
VI. Studies to Support First in Human Exposure
VII. Clinical Pathology
VIII. Reproductive Toxicology
IX. Pediatric Populations
X. Special Studies
Chapter 15: Use and Misuse of Statistics in the Design and Interpretation of Studies
I. Introduction
II. Prerequisites to Statistical Analysis
III. Functions of Statistical Analyses
IV. An Overview of Experimental Design
V. Designs Commonly Used in Toxicologic Studies
VI. Managing Data
VII. Statistical Methods
I. METHODS FOR THE REDUCTION OF DIMENSIONALITY
VIII. Data Analysis Applications in Toxicologic Pathology
IX. Summary and Conclusions
ACKNOWLEDGMENT
Chapter 16: Preparation of the Report for a Toxicology/Pathology Study
I. Introduction
II. Clients
III. Impact of a Poorly Written Report
IV. Preparation of the Final Report for a Toxicology Study
V. Organization of the Report
VI. Conclusion
PART C: Selected Topics in Toxicologic Pathology
Chapter 17: Risk Assessment: The Changing Paradigm
I. Introduction
II. Traditional Risk Assessment
III. The Changing Paradigm
IV. Examples of Mechanistically Based Risk Assessment
V. Future Implications and Methodologies for Toxicology
Chapter 18: Principles of Risk Communication: Building Trust and Credibility with the Public
I. Introduction
II. The Risk Communication Perspective
III. Risk Communication and Public Involvement
IV. Challenges and Obstacles to Effective Risk Communication
V. Perception and Acceptance of Risk
VI. Assessing the Issue: “Is There a Risk?”
VII. How Can Risks Be Managed?
VIII. Putting It All Together
IX. Summary
ACKNOWLEDGMENTS
Chapter 19: Biomedical Devices and Biomaterials
I. Introduction
II. Definition of Biomaterial and Biomedical Devices
III. Biomedical Devices
IV. Safety Evaluation of Biomaterials and Devices
Chapter 20: Biotechnology and Its Products
I. Introduction
II. Biopharmaceuticals
III. Safety Evaluation of Biopharmaceuticals
IV. Summary and Conclusions
Chapter 21: Endocrine Disruptors
I. Introduction
II. Mechanisms of Endocrine Disruption
III. Target Organs
IV. Classes of Compounds with Endocrine-Disrupting Activity
V. Exposure to Endocrine Disruptors: Are There Risks?
VI. Techniques for Screening Endocrine Disruptors
VII. Conclusions, Controversy, and Questions
Chapter 22: Radiation and Heat
I. Introduction
II. Ionizing Radiation
III. Ultraviolet Radiation
IV. Hyperthermia
Chapter 23: Nutritional Toxicologic Pathology
I. Introduction
II. Macronutrients
III. Micronutrients
IV. Dietary Contaminants
Chapter 24: Phycotoxins
I. Introduction
II. Diarrheic Shellfish Poisoning
III. Paralytic Shellfish Poisoning
IV. Amnesic Shellfish Poisoning
V. Ciguatera Fish Poisoning
VI. Pfiesteria Toxicoses
VII. Cyanobacterial Toxins
Chapter 25: Selected Mycotoxins Affecting Animal and Human Health
I. Introduction
II. Aflatoxins
III. Ochratoxins
IV. Trichothecene Mycotoxins
V. Zearalenone
VI. Fumonisins
VII. Ergot Alkaloids
VIII. Summary/Conclusion
ACKNOWLEDGMENTS
Chapter 26: Heavy Metals
I. Introduction
II. Cadmium
III. Mercury
IV. Lead
V. Arsenic
VI. Uranium and Plutonium
VII. Thallium
VIII. Bismuth
IX. Antimony
X. Beryllium
XI. Summary and Conclusions
VOLUME 2: Organ-Specific Toxicologic Pathology
Chapter 27: Organ-Specific Toxicologic Pathology: An Introduction
Chapter 28: Respiratory System
I. Introduction
II. Structure and Cell Biology
III. Mechanisms of Toxicity
IV. Response to Injury
V. Testing for Toxicity
Chapter 29: Skin and Oral Mucosa
I. Skin
II. Oral Mucosa
ACKNOWLEDGMENTS
Chapter 30: Gastrointestinal Tract
I. Introduction
II. Structure and Function of the Gastrointestinal Tract
III. Mechanisms of Gastrointestinal Toxicity
IV. Response of the Gastrointestinal Tract to Injury
V. Evaluation of Gastrointestinal Toxicity
Chapter 31: Liver
I. Introduction
II. Structure and Function
III. Cellular Mechanisms of Toxicity
IV. Nonneoplastic Responses to Injury
V. Hepatic Neoplasia
VI. Testing for Toxicity
VII. Summary and Conclusions
Chapter 32: Pancreas
I. Overview
II. Exocrine Pancreas
III. Endocrine Pancreas
Chapter 33: Kidney
I. Introduction
II. Renal Structure and Function
III. Molecular Pathology of the Kidney
IV. Mechanisms of Toxicity
V. Response To Injury
VI. Testing for Kidney Toxicity
VII. Conclusion
ACKNOWLEDGMENTS
Chapter 34: Lower Urinary Tract
I. Introduction
II. Structure and Function
III. Mechanisms of Toxicity
IV. Response to Injury
V. Testing for Toxicity
Chapter 35: Cardiovascular and Skeletal Muscle Systems
I. Heart
II. Vessels
III. Skeletal Muscle
Chapter 36: Bones and Joints
I. Introduction
II. Skeletal Structure and Composition
III. Bone Physiology and Function
IV. Mechanisms of Toxicity
V. Response of the Skeleton to Toxic Injury
VI. Evaluation of Skeletal Toxicity
VII. Summary
Chapter 37: Nervous System
I. Introduction
II. Structure and Function of the Nervous System
III. Mechanisms of Disease and Classification of Neurotoxic Diseases
IV. Testing for Neurotoxicity
V. Conclusions
Chapter 38: The Eye
I. Introduction
II. Development of the Eye
III. Cornea
IV. Lens
V. Retina and Retinal Pigment Epithelium
VI. Toxicologic, Clinical, and Pathologic Evaluation
VII. Ocular Toxicity Testing
VIII. Conclusions
Chapter 39: Immune System
I. Introduction
II. Structure and Function of the Immune System
III. Mechanisms of Immune Toxicity
IV. Response of Lymphoid Tissue to Toxic Injury
V. Inflammation in Nonlymphoid Organs: Autoimmune Disease and Allergy
VI. Testing for Immunotoxicity
VII. Summary
Chapter 40: Hematopoietic System
I. Introduction
II. Phylogeny and Ontogeny of the Hematopoietic and Lymphoid Systems
III. Structure and Function
IV. Hematopoietic Assessment
V. Interpreting Changes in Blood and Hematopoietic Tissues
VI. Hematotoxic Agents and Mechanisms
VII. Summary and Future Direction
ACKNOWLEDGMENTS
Chapter 41: Endocrine System
I. Introduction
II. Adrenal Cortex
III. Adrenal Medulla
IV. Pituitary Gland
V. Thyroid C Cells
VI. Thyroid Follicular Cells
VII. Parathyroid Gland
Chapter 42: Male Reproductive System
I. Introduction
II. Structure and Cell Biology
III. Mechanisms of Toxicity
IV. Responses to Injury
V. Testing for Toxicity
VI. Conclusions
Chapter 43: Female Reproductive System
I. Introduction
II. Structure and Functional Physiology
III. Mechanisms of Toxicity
IV. Response to Injury
V. Testing for Toxicity
VI. Summary
Chapter 44: Embryo and Fetus
I. Introduction
II. Normal Morphologic Development
III. Mechanisms of Toxicity
IV. Response to Injury
V. Selected Malformations
VI. Developmental Toxicity Testing and Risk Assessment
Index
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