Haschek and Rousseaux’s Handbook of Toxicologic Pathology 4th Edition by Brad Bolon,Matthew Wallig,Wanda Haschek,Colin Rousseaux 9780128218297 0128218290

Chapter 1. Toxicologic Pathology: An Introduction

1. An Overview of Toxicologic Pathology

2. What Is Toxicologic Pathology?

3. The Basis of Toxicologic Pathology

4. Challenges in Toxicologic Pathology

5. Training and Certification in Toxicologic Pathology

6. The “Practitioner” of Toxicologic Pathology

7. Summary

Part 1. Principles of Toxicologic Pathology

Chapter 2. Biochemical and Molecular Basis of Toxicity

1. Introduction

2. General Principles of Xenobiotic Disposition

3. Interactions of Toxicants with Cellular and Molecular Targets

4. Idiosyncratic Mechanisms of Toxicity

5. Protective Mechanisms, Repair Mechanisms, and Adaptation or Failure

6. Summary and Conclusions

Chapter 3. ADME Principles in Small Molecule Drug Discovery and Development: An Industrial Perspective

1. Introduction

2. General ADME Principles

3. Discovery Overview

4. Absorption, Bioavailability, and PK/TK Studies

5. Distribution

6. Metabolism

7. Excretion

8. Physiologically Based PK modeling

9. Development

10. Mass Balance Studies

11. Tissue Distribution Studies

12. Drug Metabolism Studies in Development

13. Excretion Studies

14. Specialized Excretion Studies

15. General Timing of Development ADME Studies

16. Conclusions

Chapter 4. Biotherapeutics ADME and PK/PD Principles

1. Introduction

2. Pharmacokinetics of Biotherapeutics

3. Pharmacodynamics of Biotherapeutics

4. PK–PD Modeling and Interspecies Scaling

5. Summary

Chapter 5. Principles of Pharmacodynamics and Toxicodynamics

1. Introduction: Definition of Pharmacodynamics and Toxicodynamics

2. Mechanism of Drug Action and Adverse Drug Reaction

3. Types of Adverse Drug Reaction: Intrinsic (Type A) Versus Idiosyncratic (Type B)

4. Types of Xenobiotic–Target Interaction

5. Exposure-Dependent Response

6. Response Following Chronic Dosing

7. Quantitative Modeling for Pharmacokinetic/Pharmacodynamic and Toxicodynamic Data Analysis

Chapter 6. Morphologic Manifestations of Toxic Cell Injury

1. Introduction

2. Adaptation

3. Irreversible versus Reversible Cell Injury

4. Irreversible Cell Injury

5. Conclusion

Chapter 7. The Role of Pathology in Evaluation of Reproductive, Developmental, and Juvenile Toxicity

1. Introduction

2. Reproductive Toxicity Assessment

3. Pregnancy and Developmental Toxicity

4. Juvenile Toxicity Assessment

5. Conclusions

Abbreviations

Chapter 8. Carcinogenesis: Mechanisms and Evaluation

1. Introduction

2. Mechanisms of Chemically Induced Carcinogenesis

3. Identification of Carcinogens—Testing Programs and Guidelines

4. Evolving and New Technologies

5. Conclusions

Part 2. Methods in Toxicologic Pathology

Chapter 9. Basic Approaches in Anatomic Toxicologic Pathology

1. Introduction

2. General Considerations in Study Protocol Development

3. In-Life Evaluations

4. Necropsy

5. Fixation and Histologic Procedures

6. Specialized Histologic Techniques

7. Histopathologic Evaluation

8. Artifacts versus Lesions

9. Diagnostic Challenges in Anatomic Toxicologic Pathology

10. Conclusions

Chapter 10. Clinical Pathology in Nonclinical Toxicity Testing

1. Introduction

2. Clinical Pathology Parameters Commonly Included in Protocols for General Toxicity Studies

3. Nonstandard Biomarkers

4. Conclusions

Chapter 11. Special Techniques in Toxicologic Pathology

1. Introduction

2. Immunohistochemistry

3. Enzyme Histochemistry

4. In Situ Hybridization

5. Flow Cytometry

6. Laser Capture Microdissection

7. Confocal Microscopy

8. Electron Microscopy

9. Stereology

10. Digital Pathology

11. Conclusions

Glossary

Chapter 12. Digital Pathology and Tissue Image Analysis

1. Introduction

2. Whole-Slide Imaging

3. Tissue Image Analysis

4. Regulatory Considerations for Digital Pathology Evaluation

5. Related Topics

6. Conclusion

Chapter 13. In Vivo Small Animal Imaging: A Comparison to Gross and Histopathologic Observations in Animal Models

1. Introduction

2. Magnetic Resonance Imaging and Magnetic Resonance Microscopy

3. Computed Tomography

4. Radionuclide-based Imaging: PET and SPECT

5. Optical Imaging

6. Ultrasound

7. Translational Application, Safety Assessment, and Drug Screening with In Vivo or Ex Vivo Imaging

Abbreviations for Imaging Modalities

Chapter 14. Biomarkers: Discovery, Qualification, and Application

1. Introduction

2. Categories of Biomarkers

3. Strategies for Discovery of Biomarkers

4. Methods for Biomarker Measurement and Quantitation

5. Qualification of Biomarkers: Major Considerations

Chapter 15. Toxicogenomics: A Primer for Toxicologic Pathologists

1. Introduction

2. Basics of Toxicogenomics

3. Overview of Toxicogenomic Technologies

4. Key Considerations for Conducting Toxicogenomic Studies

5. Goals and Applications of Toxicogenomic Studies

6. Sample Considerations

7. Applications of Toxicogenomics

8. Regulatory Considerations

9. Conclusions

Glossary

Chapter 16. Experimental Design and Statistical Analysis for Toxicologic Pathologists

1. Introduction

2. Considerations Made Before Designing the Experiment

3. Experimental Design

4. Designs Commonly Used in Toxicologic Pathology

5. Functions of Statistical Analyses

6. Prerequisites to Statistical Analysis

7. Statistical Methods

8. Interpretation of Results

9. Data Analysis Applications in Toxicologic Pathology

10. Assumptions of Statistical Tests

11. Summary and Conclusions

Glossary

Part 3. Animal and Alternative Models in Toxicologic Research

Chapter 17. Animal Models in Toxicologic Research: Rodents

1. Introduction

2. Rodent Model Selection

3. Issues in Extrapolation of Rodent Data for Human Risk Assessment

4. Basic Biological Characteristics of Common Rodent Stocks and Strains

5. Common Pathologic Findings in Rodents

6. Conclusion

Chapter 18. Animal Models in Toxicologic Research: Rabbit

1. Introduction

2. Model Selection

3. Basic Biological Characteristics and Common Breeds

4. Regulatory Aspects and Examples of Use of Rabbits in Biomedical Research

5. Pharmacokinetic and Toxicity Studies

6. Major Disease and Functional Models (Other than Safety)

7. Spontaneous Findings in the Experimental NZW Rabbit

Chapter 19. Animal Models in Toxicologic Research: Dog

1. Introduction

2. History and Derivation of Beagles

3. Use of Dogs in Biomedical Research

4. Predictivity of Dog Toxicity Data to Humans

5. Comparative Toxicology of the Dog

6. Spontaneous Background Pathology in the Beagle (Refer to Woicke et al., 2021)

7. Use of the Dog as a Model of Human Diseases

8. Regulatory Considerations for Toxicity Studies

9. Ethics of Use of the Dog as a Laboratory Animal Species

10. Summary

Chapter 20. Animal Models in Toxicologic Research: Pig

1. Introduction

2. Genetics of Pigs and Background for Their Use in Research

3. Use of Pigs in Toxicological Studies

4. Pigs as Organ Source for Xenotransplantation

5. Spontaneous Background Pathology in Swine

6. Use of the Pig as a Model System for Medical Devices and of Human Diseases

7. Regulatory Aspects

8. Ethics and Animal Welfare

9. Summary

Chapter 21. Animal Models in Toxicologic Research: Nonhuman Primate

1. Introduction

2. History and Biological Characteristics of Nonhuman Primates

3. Selection of Nonhuman Primates for Toxicologic Research and Study Design Considerations

4. Predictivity of Nonhuman Primate Toxicity Data to Humans

5. Nonhuman Primate Models in Biomedical Research (see also (Abee, Mansfield, Tardif, & Morris, 2012)

6. Background Findings in Nonhuman Primates and Use of Historical Control Data

7. Conclusion

Chapter 22. Animal Models in Toxicologic Research: Nonmammalian

1. Introduction

2. Nonmammalian Animal Taxa

3. Utilization of Nonmammalian Animals

4. Study Design Considerations

5. Data Extrapolation

6. Conclusions

Chapter 23. Genetically Engineered Animal Models in Toxicologic Research

1. Fundamentals of Genetically Engineered Animal Models

2. Analysis of Genetically Engineered Animal Models

3. Genetically Modified Models for Hazard Identification and Safety Assessment

4. Limitations in Using Genetically Modified Animals for Hazard Identification and Safety Assessment

5. Special Considerations in Safety Assessment of Products Derived from Genetically Engineered Animals

6. Summary

Glossary

Chapter 24. Alternative Models in Biomedical Research: In Silico, In Vitro, Ex Vivo, and Nontraditional In Vivo Approaches

1. Introduction

2. Nontraditional Models in Toxicity Research

3. In Vitro and Ex Vivo Models

4. In Silico Models and Data Analytics

5. In Vivo Models Using Alternative Mammalian and Nonmammalian Species

6. Regulatory Perspective on Alternative Models

7. Conclusions and Perspectives

Part 4. Practice of Toxicologic Pathology

Chapter 25. Nomenclature and Diagnostic Resources in Anatomic Toxicologic Pathology

1. Introduction

2. The Need for Standardized Nomenclature

3. Components in Nomenclature

4. Challenges in Standardizing Nomenclature

5. Recommended Practices

6. Harmonization of Nomenclature

7. Conclusions

Chapter 26. Pathology Peer Review

1. Introduction

2. Peer Review Timing and Pathology Raw Data

3. Peer Review Process

4. National Toxicology Program Review Process

5. Regulatory Aspects of Pathology Peer Review

6. Use of Digital/Whole-Slide Images in Pathology Peer Review

7. Conclusion

Chapter 27. Pathology and GLPs, Quality Control, and Quality Assurance

1. Introduction

2. Overview of Good Laboratory Practice Standards

3. GLP and Pathology Data

4. Clinical Pathology Assessment in the GLP Environment

5. Ultrastructural Assessment in the GLP Environment

6. Noninvasive Imaging Applications in the GLP Environment

7. In the Spirit of GLP

8. GLP Criticism

9. Conclusions

Chapter 28. Practices to Optimize Generation, Interpretation, and Reporting of Pathology Data from Toxicity Studies

1. Introduction

2. Practices that Prevent or Mitigate the Introduction of Pathology-Related Issues During Study Design and Protocol Preparation

3. Practices that Prevent or Mitigate the Introduction of Pathology-Related Issues Arising During the In-Life Phase

4. Practices that Prevent or Mitigate Issues Arising from Pathology Assessment and Reporting

5. Conclusions

Glossary

Chapter 29. Issues in Laboratory Animal Science That Impact Toxicologic Pathology

1. Introduction

2. Trends in Global Research Animal Care and Use

3. Regulatory Issues

4. Euthanasia of Research Animals

5. Selection of Animal Models

6. Animal Health Considerations

7. Microbiome and Microbial Effects on Pathophysiology and Study Outcomes

8. Housing and Husbandry Issues

9. The Role of Diet in Toxicity Studies

10. 3R’s and In-Life Study Conduct for the Toxicologic Pathologist

11. Description of Animal Studies in Scientific Publications

12. Conclusion