eBook Haschek and Rousseaux’s Handbook of Toxicologic Pathology, 1st Edition

  • Published By:
  • ISBN-10: 0124157653
  • ISBN-13: 9780124157651
  • DDC: 615.9
  • Grade Level Range: College Freshman - College Senior
  • 3054 Pages | eBook
  • Original Copyright 2013 | Published/Released February 2014
  • This publication's content originally published in print form: 2013
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About

Overview

Haschek and Rousseaux’s Handbook of Toxicologic Pathology is a key reference on the integration of structure and functional changes in tissues associated with the response to pharmaceuticals, chemicals and biologics. The 3e has been expanded by a full volume, and covers aspects of safety assessment not discussed in the 2e. Completely revised with many new chapters, it remains the most authoritative reference on toxicologic pathology for scientists and researchers studying and making decisions on drugs, biologics, medical devices and other chemicals, including agrochemicals and environmental contaminants. New topics include safety assessment, the drug life cycle, risk assessment, communication and management, carcinogenicity assessment, pharmacology and pharmacokinetics, biomarkers in toxicologic pathology, quality assurance, peer review, agrochemicals, nanotechnology, food and toxicologic pathology, the environment and toxicologic pathology and more.

Table of Contents

Front Cover.
Half Title Page.
Title Page.
Copyright Page.
Dedication.
Contents.
Preface to the Third Edition.
About the Editors.
Contributors.
Toxicologic Pathology: An Introduction.
An Overview of Toxicologic Pathology.
Suggested Reading.
Other Frontmatter.
1: Principles of Toxicologic Pathology.
2: Biochemical and Molecular Basis of Toxicity.
3: Introduction.
4: General Principles of Xenobiotic Disposition.
5: Interactions of Toxicants with Cellular and Molecular Targets.
6: Protective Mechanisms, Repair Mechanisms and Adaptation.
7: Summary and Conclusions.
8: Suggested Reading.
9: Pharmacokinetics and Toxicokinetics.
10: Introduction.
11: Pharmacokinetics: Processes and Determinants.
12: Pharmacokinetic (Time-Course) Data and Derivation of Dose Metrics.
13: Pharmacokinetic Models and Computation of Dose Metrics.
14: Pharmacokinetics and Its Use in Designing Toxicity Studies.
15: Pharmacokinetics and Interpretation of Bioassay Outcomes.
16: Concluding Remarks.
17: Suggested Reading.
18: Principles of Pharmacodynamics and Toxicodynamics.
19: Introduction: Pharmacodynamics and Toxicodynamics Defined.
20: Relevance of PD and TD to Toxicological Pathology.
21: Mechanisms of Drug Action: General Categories.
22: Cellular Processes Linking Drug Concentration and Receptor Binding to Cellular Effect.
23: Characterizing Biological Effects of a Drug or Toxin.
24: Reversible Two-State Model of Receptor Activation.
25: Selectivity and Safety: Therapeutic Vs Toxic Effect of Drugs.
26: Principles of Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling.
27: Summary.
28: Suggested Reading.
29: Morphologic Manifestations of Toxic Cell Injury.
30: Introduction.
31: Reversible Cell Injury.
32: Irreversible Injury.
33: Concluding Comments.
34: Suggested Reading.
35: Carcinogenesis: Mechanisms and Manifestations.
36: Introduction.
37: Cancer Is a Genetic Disease.
38: Identifying Carcinogens.
39: Conclusions.
40: Suggested Reading.
41: Methods in Toxicologic Pathology.
42: Basic Approaches in Anatomic Toxicologic Pathology.
43: Introduction.
44: General Considerations In Study Protocol Development.
45: In-Life.
46: Necropsy.
47: Fixation and Histologic Procedures.
48: Specialized Histologic Techniques.
49: Histopathology.
50: Artifacts Versus Lesions.
51: Lesion Interpretation.
52: Conclusions.
53: Suggested Reading.
54: Special Techniques in Toxicologic Pathology.
55: Introduction.
56: Immunohistochemistry.
57: In Situ Hybridization (ISH).
58: Flow Cytometry.
59: Laser Microdissection.
60: Confocal Microscopy.
61: Digital Pathology.
62: Suggested Reading.
63: Stereological Principles and Sampling Procedures for Toxicologic Pathologists.
64: Application of Design-Based Stereology in Toxicologic Pathology.
65: Stereology – Basic Concepts and Sampling Designs.
66: The Stereological Estimators of Structural 3D Quantities.
67: Optimizing the Sampling Procedure in a Given Experiment.
68: Appendices.
69: Suggested Reading.
70: In Vivo Small Animal Imaging: A Comparison with Gross and Histopathologic Observations in Animal Models.
71: Introduction.
72: Magnetic Resonance Imaging (MRI) and Magnetic Resonance Microscopy (MRM).
73: Computed Tomography (CT).
74: Micro-CT Microscopy.
75: Radionuclide-Based Imaging: PET and SPECT.
76: Optical Imaging.
77: Ultrasound.
78: Translational Application, Safety Assessment, and Drug Screening with in Vivo or Ex Vivo Imaging.
79: Suggested Reading.
80: Biomarkers: Discovery, Qualification and Application.
81: Introduction.
82: Categories of Biomarkers.
83: Strategies for Discovery of Biomarkers.
84: Methods for Biomarker Measurement and Quantitation.
85: Qualification of Biomarkers: Major Considerations.
86: Suggested Reading.
87: The Application of Toxicogenomics to the Interpretation of Toxicologic Pathology.
88: Introduction.
89: Why Toxicogenomics?.
90: Key strengths and Weaknesses of Toxicogenomics.
91: Terminology and Platforms For Toxicogenomics.
92: Key Issues in Conducting Toxicogenomic Studies.
93: Examples of Key Toxicogenomic Studies.
94: Directions of Toxicogenomics for the Next Decade.
95: Additional Data.
96: Suggested Reading.
97: Genetically Engineered Animals in Product Discovery and Development.
98: Fundamentals of Genetically Engineered Animal Models.
99: Analysis of Genetically Engineered Animal Models.
100: Genetically Modified Models for Non-Clinical Safety Assessment.
101: Limitations in Using Genetically Modified Animals for Non-Clinical Safety Testing.
102: Special Considerations in Safety Assessment of Products Derived from Genetically Engineered Animals.
103: Summary.
104: Glossary.
105: Suggested Reading.
106: The Use of Minipigs in Non-Clinical Research.
107: Introduction.
108: Regulatory Aspects.
109: Minipig Strains.
110: Ethics and Animal Welfare.
111: Animals.
112: Parameters for Evaluation in Safety Studies Performed in Swine.
113: Studies.
114: Other Routes of Dose Administration.
115: Spontaneous Pathology in the Experimental Gottingen Minipig.
116: Neoplasia in Research Swine.
117: Suggested Reading.
118: Alternative Animal Models.
119: Introduction.
120: Utilization of Alternative Animals.
121: Alternative Animal Taxa.
122: Special Considerations.
123: Conclusions.
124: Suggested Reading.
125: Pathology and GLPs, Quality Control and Quality Assurance.
126: Introduction.
127: Good Laboratory Practice.
128: GLP and Pathology Data.
129: In the Spirit of GLP.
130: GLP Criticism.
131: Suggested Reading.
132: Practice of Toxicologic Pathology.
133: Nomenclature.
134: Background and Introduction.
135: The Need for Standardized Nomenclatures.
136: Components in Nomenclature.
137: Challenges in Standardizing Nomenclature.
138: Suggested Practices.
139: Harmonization of Nomenclature.
140: Summary.
141: Suggested Reading.
142: Peer Review and Pathology Working Groups.
143: Introduction.
144: What Are the Qualifications of the Peer Review Pathologist?.
145: Are Peer Reviews Required?.
146: How Is a Peer Review Conducted?.
147: Prospective Peer Reviews.
148: Retrospective Peer Review.
149: Peer Review Statement.
150: Documentation of the Peer Review and Data Locking.
151: Sources of Disagreement in Peer Reviews.
152: Digital Peer Reviews.
153: Pathology Working Group.
154: Suggested Reading.
155: Clinical Pathology in Non-Clinical Toxicology Testing.
156: Introduction.
157: Parameters Commonly Included in General Toxicology Study Protocols.
158: Additional Available Tests.
159: Novel Biomarkers.
160: Conclusions.
161: Suggested Reading.
162: Pathology Issues in the Design of Toxicology Studies.
163: Introduction.
164: Discovery Studies.
165: Regulatory Studies.
166: Carcinogenicity Studies.
167: Special Studies: Animal Health Products.
168: Summary and Conclusions.
169: Suggested Reading.
170: Issues in Laboratory Animal Science.
171: Introduction.
172: Recent Trends in Global Research Animal Care and Use.
173: Regulatory Issues.
174: Euthanasia of Research Animals.
175: Selection of Animal Models.
176: Animal Health Considerations.
177: Housing and Husbandry Issues.
178: The Role of Diet in Toxicology Studies.
179: 3Rs for the Toxicologic Pathologist.
180: Description of Animal Studies in Scientific Publications.
181: Summary.
182: Suggested Reading.
Half Title Page.
Title Page.
Contents.
Other Frontmatter.
1: Safety Assessment in Toxicologic Pathology: An Introduction.
2: Toxicologic Pathology in Product Discovery and Safety Assessment.
3: Overview of Drug Development.
4: Introduction.
5: Overview.
6: Drug Discovery and Development.
7: Development.
8: Non-Clinical Studies (Safety).
9: Efficacy (E).
10: Clinical Trials.
11: Post-Marketing Surveillance.
12: Regulatory Authorities.
13: Summary and Conclusions.
14: Suggested Reading.
15: Overview of the Role of Pathology in Product Discovery and Safety Assessment.
16: Introduction.
17: Pathologists' Contributions in Drug Discovery.
18: History of Pharmaceutical Regulatory Oversight in Drug Development.
19: Designing Studies to Assess Human Risk with Typical Drug Candidates.
20: Development with Biological Drug Candidates.
21: Unique Requirements for Anticancer Drug Candidates.
22: Optimal Animal Dose Selection Enhances Clinical Study Design.
23: Pathologist's Role in Special Toxicity Studies.
24: Suggested Reading.
25: Discovery Toxicology and Pathology.
26: Introduction.
27: Knowledge Integration and the Spanning of Disciplines.
28: Pathology Toolbox.
29: In Vitro/in Vivo Correlations.
30: Hypothesis Generation, Experimental Design, and the Role of Investigative Studies.
31: Target Validation and in Vivo Relevance of Target Selectivity.
32: Discovery Strategy for Biologics.
33: Communications.
34: Personality and Behavioral Traits that are Helpful to Succeed in Discovery Pathology and Discovery Toxicology.
35: Conclusion.
36: Suggested Reading.
37: Pathology in Non-Clinical Drug Safety Assessment.
38: Introduction.
39: Drug Safety and Efficacy are Continuum.
40: The Pathologist's Role in Non-Clinical Safety Assessment.
41: Pathology in Non-Clinical Safety Assessment of Small Molecules.
42: Pathology in Non-Clinical Safety Assessment of Biotherapeutics.
43: Pathology in Non-Clinical Safety Assessment of Novel Formulations.
44: Reversibility and Delayed Toxicity.
45: GLP Regulations and Pathology.
46: Imaging and Its Use in Non-Clinical Safety Assessment.
47: Novel Scientific Tools in Non-Clinical Safety Assessment.
48: Future Challenges in Non-Clinical Safety Assessment.
49: Suggested Reading.
50: Biopharmaceuticals.
51: Introduction.
52: Biopharmaceuticals.
53: Safety Evaluation Strategies for Biopharmaceuticals.
54: Summary and Conclusions.
55: Suggested Reading.
56: Biomedical Materials and Devices.
57: Introduction.
58: Definition of Biomaterials and Biomedical Devices.
59: Biomedical Devices.
60: Safety and Toxicology of Biomaterials and Devices.
61: Conclusion.
62: Suggested Reading.
63: Carcinogenicity Assessment.
64: A Brief History of Carcinogenicity Assessment.
65: Planning, Prerequisite Information, and Timing of Lifetime Carcinogenicity Studies.
66: Two-Year Rodent Carcinogenicity Studies.
67: Alternative Genetically Modified Mouse Models.
68: Carcinogenicity Assessment of Biotechnology-Derived Therapeutic Proteins.
69: Carcinogenicity Assessment of Nucleic Acid Therapies.
70: Carcinogenicity Assessment of Stem Cell-Derived Therapies.
71: Summary.
72: Suggested Reading.
73: Safety Assessment and Data Interpretation.
74: Preparation of the Pathology Report for a Toxicology Study.
75: Introduction.
76: Clients for the Pathology Report.
77: Objective of the Pathology Report.
78: Developing the Data for the Pathology Report.
79: Text Tables.
80: Discussion.
81: Conclusion for the Pathology Report.
82: Signing the Pathology Report.
83: Examples to Be Avoided in Presenting/Interpreting Data in the Pathology Report.
84: Methods to Prevent or Resolve Issues.
85: Peer Review.
86: Overall Conclusion for the Chapter.
87: Suggested Reading.
88: Interpretation of Clinical Pathology Results in Non-Clinical Toxicology Testing.
89: Introduction.
90: Hematology Interpretation.
91: Interpretation of Bone Marrow Cytology.
92: Coagulation Interpretation.
93: Clinical Chemistry Interpretation.
94: Urinalysis and Urine Chemistry Interpretation.
95: Microsomal Induction Interpretation.
96: Overall Results Interpretation.
97: Tying It All Together: Reporting, Terminology and use of Clinical Terms.
98: Conclusions.
99: Suggested Reading.
100: Statistical Assessment of Toxicologic Pathology Studies.
101: Introduction.
102: Prerequisites to Statistical Analysis.
103: Functions of Statistical Analyses.
104: Experimental Design.
105: Designs Commonly Used in Toxicologic Pathology.
106: Managing the Data.
107: Statistical Methods.
108: Data Analysis Applications in Toxicologic Pathology.
109: Assumptions Statistical Tests.
110: Summary and Conclusions.
111: Glossary.
112: Suggested Reading.
113: Risk Assessment.
114: Introduction.
115: Classical Risk Assessment.
116: Contemporary Risk Assessment.
117: New Strategies and Advanced Technologies for Toxicology.
118: Risk Communication for Toxicologic Pathologists.
119: Introduction.
120: Understanding the Audience.
121: General Principles: The Science of Risk Communication.
122: Role of Animal Data in Risk Communication – Pharmaceutical Safety Assessment.
123: Putting It All Together.
124: Suggested Reading.
125: Risk Management in Non-Clinical Drug Development.
126: Introduction.
127: Definition of Risk.
128: How to Evaluate Risk.
129: Managing the Identified Risks.
130: Summary and Conclusions.
131: Suggested Reading.
132: Food and the Environment: Selected Toxic Agents.
133: Environmental Toxicologic Pathology and Human Health.
134: Introduction.
135: History and Principles.
136: Examples of Environmental Pollutants.
137: The Role of Lifestyle and the Environment on Human Health.
138: Methods of Toxicity and Carcinogenicity Testing.
139: Current Considerations for Environmental Toxicity and Carcinogenicity Testing.
140: New Directions for Environmental Toxicity and Carcinogenicity Testing.
141: Suggested Reading.
142: Food and Toxicologic Pathology: An Overview.
143: Introduction.
144: General Concepts in Food Toxicology.
145: Food Additives.
146: Environmental Contaminants.
147: Contaminants Arising or Introduced during Food Processing and Packaging.
148: Natural Toxins.
149: Compounds That are Intrinsic Constituents of Food, But Which are Harmful to A Susceptible Population.
150: Molecular Pathology: Biomarkers and Their Applications to Food Toxicology.
151: Challenges and Future Developments in Food Safety.
152: Suggested Reading.
153: Nutritional Toxicologic Pathology.
154: Introduction.
155: Caloric Excess and Obesity.
156: Caloric Restriction.
157: Macronutrients and Micronutrients.
158: Dietary Contaminants.
159: Suggested Reading.
160: Endocrine Disruptors.
161: Introduction.
162: Mechanisms of Endocrine Disruption.
163: Edc Effects on Estrogen Signaling.
164: EDC Effects on Androgen Signaling.
165: EDC Effects on Steroid Hormone Production Or on the Hypothalamo-Pituitary-Gonadal Axis.
166: EDC Effects on Thyroid Hormone Signaling.
167: EDC Effects on Glucocorticoid Signaling.
168: EDCS That Have Effects on Adipose Deposition/Obesity and Diabetes.
169: Epigenetic Effects of EDCs.
170: How Do We Know If Chemical is an Environmental Endocrine Disruptor, and What We Do If It is?.
171: Future Methodologies.
172: Integrative Assessment Programs and the Future of Endocrine Disruption Screening.
173: Regulatory Matters.
174: Why is it Difficult to Assess Human Health Effects of EDCs?.
175: Suggested Reading.
176: Phycotoxins.
177: Introduction.
178: Okadaic Acid and Dinophysistoxins.
179: Saxitoxins.
180: Domoic Acid.
181: Brevetoxins.
182: Ciguatoxins.
183: Azaspiracid Toxins.
184: Cylindrospermopsin.
185: Microcystins and Nodularin.
186: Anatoxins.
187: Cyclic Imines.
188: Lyngbya Majuscula.
189: β-Methylamino-L-Alanine.
190: Concluding Remarks.
191: Suggested Reading.
192: Mycotoxins.
193: Introduction.
194: Aflatoxins.
195: Ochratoxins.
196: Trichothecene Mycotoxins.
Half Title Page.
Title Page.
Contents.
Other Frontmatter.
Organ-Specific Toxicologic Pathology: An Introduction.
1: Food and the Environment: Selected Toxic Agents.
2: Liver and Gall Bladder.
3: Introduction.
4: Structure, Function, and Cell Biology.
5: Evaluation of Liver Toxicity.
6: Response to Injury.
7: Mechanisms of Toxicity in Liver.
8: Summary.
9: Suggested Reading.
10: Cardiac, Vascular, and Skeletal Muscle Systems.
11: Introduction.
12: Heart.
13: Structure and Function.
14: Evaluation of Toxicity: Heart.
15: Response to Injury.
16: Mechanisms of Toxicity.
17: Blood Vessels.
18: Structure and Function.
19: Evaluation of Toxicity: Vasotoxic Effects.
20: Response to Injury.
21: Mechanisms of Toxicity.
22: Skeletal Muscle.
23: Structure and Function.
24: Evaluation of Toxicity: Skeletal Muscle.
25: Response to Injury.
26: Mechanisms of Toxicity.
27: Summary.
28: Suggested Reading.
29: Kidney.
30: Introduction.
31: Structure, Function, and Cell Biology.
32: Evaluation of Toxicity.
33: Response to Injury.
34: Mechanisms of Toxicity.
35: Suggested Reading.
36: Lower Urinary Tract.
37: Introduction.
38: Structure, Function and Cell Biology.
39: Evaluation of Toxicity.
40: Response to Injury.
41: Mechanisms of Toxicity.
42: Suggested Reading.
43: Immune System.
44: Introduction.
45: Function and Structure.
46: Mechanisms and Evaluation of Toxicity.
47: Response to Injury.
48: Suggested Reading.
49: Hematopoietic System.
50: Introduction.
51: Phylogenesis and Ontogenesis.
52: Structure, Function, and Cell Biology.
53: Evaluation of Hematotoxicity.
54: Mechanisms of Toxicity.
55: Response of Hematopoietic Tissues to Injury.
56: Suggested Reading.
57: Respiratory System.
58: Introduction.
59: Structure, Function, and Cell Biology.
60: Testing for Toxicity.
61: Response to Injury.
62: Mechanisms of Toxicity.
63: Conclusion.
64: Suggested Reading.
65: Nervous System.
66: Introduction.
67: Anatomy and Function of the Nervous System.
68: Evaluation of Neurotoxicity.
69: Response to Neurotoxic Injury.
70: Mechanisms of Nervous System Injury.
71: Summary.
72: Suggested Reading.
73: Eye.
74: Introduction.
75: Biological and Anatomic Features Unique to the Mammalian Eye.
76: Toxicological, Clinical, and Pathological Evaluation of the Eye.
77: Fundamentals of the Morphologic Examination of Ocular Tissues.
78: Eyelids.
79: Lacrimal System.
80: Precorneal Tear Film.
81: Cornea and Conjunctiva.
82: Uvea and Filtration Apparatus.
83: The Lens.
84: The Vitreous Body.
85: Retina and Retinal Pigment Epithelium (Rpe).
86: Optic Nerve.
87: Glaucoma.
88: Summary.
89: Glossary.
90: Suggested Reading.
91: Ear.
92: Introduction.
93: Structure and Function.
94: Evaluation of Otic Toxicity.
95: Responses to Injury and Mechanisms of Injury.
96: Conclusions.
97: Suggested Reading.
98: Integument.
99: Introduction.
100: Structure and Function.
101: Evaluation of Toxicity.
102: Response to Injury.
103: Mechanisms of Toxicity.
104: Suggested Reading.
105: Digestive Tract.
106: Introduction.
107: Structure and Function of the Gastrointestinal Tract.
108: Evaluation of Gastrointestinal Toxicity.
109: Response of the Gastrointestinal Tract to Injury.
110: Mechanisms of Gastrointestinal Toxicity.
111: Suggested Reading.
112: Exocrine Pancreas.
113: Introduction.
114: Normal Structure and Function.
115: Evaluation of Toxicity.
116: Responses to Injury.
117: Mechanisms of Toxicity.
118: Suggested Reading.
119: Endocrine System.
120: Introduction.
121: Adrenal Cortex.
122: Structure and Function.
123: Mechanisms of Toxicity.
124: Response to Injury.
125: Testing for Toxicity.
126: Adrenal Medulla.
127: Structure and Function.
128: Mechanisms of Toxicity.
129: Response to Injury.
130: Testing for Toxicity.
131: Pituitary Gland.
132: Structure and Function.
133: Mechanisms of Toxicity.
134: Response to Injury.
135: Testing for Toxicity.
136: Thyroid C Cells.
137: Structure and Function.
138: Mechanisms of Toxicity.
139: Response to Injury.
140: Thyroid Follicular Cells.
141: Structure and Function.
142: Mechanisms of Toxicity.
143: Response to Injury.
144: Evaluation of Toxicity.
145: Parathyroid Gland.
146: Introduction.
147: Structure and Function.
148: Mechanisms of Toxicity.
149: Response of Parathyroid Chief Cells to Injury.
150: Evaluation of Toxicity.
151: Endocrine Pancreas.
152: Introduction.
153: Structure and Function.
154: Mechanisms of Toxicity.
155: Response to Injury.
156: Evaluation of Toxicity.
157: Summary and Conclusions.
158: Suggested Reading.
159: Male Reproductive System.
160: Introduction.
161: Structure, Function, and Cell Biology.
162: Evaluation of Toxicity.
163: Response to Injury.
164: Mechanisms of Toxicity.
165: Suggested Reading.
166: Female Reproductive System.
167: Introduction.
168: Structure, Function, and Cell Biology.
169: Evaluation of Female Reproductive System Toxicity.
170: Response to Injury.
171: Mechanisms of Toxicity in the Female Reproductive System.
172: Suggested Reading.
173: Mammary Gland.
174: Introduction.
175: Mammary Gland Structure, Function, and Cell Biology.
176: Evaluation of Toxicity.
177: Response to Injury.
178: Mechanisms of Toxicity.
179: Conclusion.
180: Suggested Reading.
181: Appendix.
182: Embryo and Fetus.
183: Introduction.
184: Normal Morphologic Development.
185: Developmental Toxicity Testing and Risk Assessment.
186: Responses to Injury.
187: Principles of Developmental Toxicity.
188: Mechanisms of Developmental Toxicity.
189: Conclusions.
190: Glossary.
191: Suggested Reading.
192: Bone and Joints.
193: Introduction.
194: Structure, Function, and Cell Biology of Bone and Cartilage.
195: Evaluation of Toxicity.