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E-grāmata: Fundamentals of Toxicologic Pathology

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Edited by Wanda M Haschek (Professor Emerita, Dept of Veterinary Pathobiology, College of Veterinary Me), Edited by Colin G. Rousseaux, Edited by Matthew A. Wallig (Professor Emeritus, Department of Veterinary Pathobiology, College of Veterinary Medicine University of Illinois at Urbana-Champaign, Urbana, Illinois, USA)

Formāts: EPUB+DRM
Izdošanas datums: 23-Nov-2009
Izdevniecība: Academic Press Inc
Valoda: eng
ISBN-13: 9780080919324

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Formāts: EPUB+DRM
Izdošanas datums: 23-Nov-2009
Izdevniecība: Academic Press Inc
Valoda: eng
ISBN-13: 9780080919324

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Toxicologic pathology integrates toxicology and the disciplines within it (such as biochemistry, pharmacodynamics and risk assessment) to pathology and its related disciplines (such as physiology, microbiology, immunology, and molecular biology).

Fundamentals of Toxicologic Pathology Second Edition updates the information presented in the first edition, including five entirely new chapters addressing basic concepts in toxicologic pathology, along with color photomicrographs that show examples of specific toxicant-induced diseases in animals. The current edition also includes comparative information that will prove a valuable resource to practitioners, including diagnostic pathologists and toxicologists.

Recenzijas

From the first edition: "The editors have succeeded in producing a very readable, basic textbook of current toxicologic pathology...The book provides many high quality, well labeled reproductions of light and electron micrographs...This book will be an excellent resource for graduate students in toxicology, pathology, and environmental health studies. It provides a thorough organ system based overview of current knowledge and fundamental principles of toxicologic pathology, devoid of the detailed treatment of descriptive morphology and mechanisms provided in reference texts." --CHOICE

"...a very valuable toxicopathological reference source..." --A.A. Seawright in AUSTRALIAN VETERINARY JOURNAL

"...a valuable resource to practicioners, including diagnostic veteriarians. This edition focuses on providing information integrated from both toxicology and pathology dealing with the mechanisms of toxic injury and morphologic expression at subcellular, cellular and tissue levels. ...this is an 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." -- Catherine Sutcliffe, Covance Laboratories Ltd, UK" --The British Toxicology Society Newsletter, Summer 2010 Issue 36

Papildus informācija

An update to a bestselling reference on toxicologic pathology systems approach

Preface

xix

Acknowledgments

xxi

Principles of Toxicology

(8)

The Effect of the Body on the Chemical

(1)

Absorption

(1)

Passage across Membranes

(1)

Distribution

(1)

Volume of Distribution

(1)

Barriers to Distribution

(1)

Biotransformation

(1)

Phase I Metabolism

(1)

Phase II Metabolism

(1)

Enzyme Location in Toxicity

(1)

Excretion

(1)

Urinary Excretion

(1)

Biliary Excretion

(1)

Pulmonary Excretion

(1)

Interaction of Chemical and the Body

(1)

Enzyme Induction and Inhibition

(1)

Activation, Induction, or Synergism

(1)

Inhibition

(1)

Dose Dependency and Site of Action

(1)

Organ Specificity for Toxicity

(1)

Site-Specific Interactions and Toxicity

(1)

Receptors and Enzymes

(1)

Direct and Cascade Effects

(1)

Nonspecific Interations and Toxicity

(1)

Electrophiles and Covalent Binding

(1)

Further Reading

(1)

Manifestations of Toxic Cell Injury: Cell Injury/Death and Chemical Carcinogenesis

(34)

Cell Injury, Cell Death and Sequelae

(1)

Introduction

(3)

Key Cellular Components in Cell Injury

(1)

Factors Influencing Injury

(1)

Reaction of the Body to Injury

(1)

Adaptation

(2)

Reversible Cell Injury

(2)

Cell Swelling

(1)

Fatty Change

(1)

Irreversible Injury

(8)

Oncotic Necrosis

(4)

Apoptotic Necrosis

(2)

Sequelae to Irreversible Cell Injury

(2)

Concluding Comments

(1)

Chemical Carcinogenesis

(1)

Overview

(1)

Nomenclature of Neoplasms

(1)

Spectrum of Proliferative Lesions

(3)

Quantitative Cell Proliferation (Hyperplasia)

(1)

Qualitative Cell Proliferation

(1)

Preneoplasia

(1)

Neoplastic Cell Proliferation

(1)

Diagnostic Distinction between Preneoplasia, Benign Neoplasia, and Malignant Neoplasia

(1)

Steps in the Neoplastic Process

(2)

Initiation

(1)

Promotion

(1)

Progression

(1)

Hypotheses of Mode of Action of Chemical Carcinogens

(3)

Overview

(1)

Mutational Genetic Hypothesis of Chemical Carcinogenesis

(1)

Nonmutational Genetic Hypothesis of Chemical Carcinogenesis

(1)

Epigenetic Hypothesis of Chemical Carcinogenesis

(1)

Viral Hypothesis of Carcinogenesis

(1)

Oncogenes and Tumor Suppressor Genes in Chemical Carcinogenesis

(3)

Genes and Oncogenes

(1)

Proto-oncogene Function

(1)

Proto-oncogene Activation

(1)

Oncogene Activation in Chemical Carcinogenesis

(2)

Tumor Suppressor Genes and Carcinogenesis

(1)

Cell Cycle and Carcinogenesis

(1)

Cyclins and Cdk Proteins

(1)

Retinoblastoma Checkpoint

(1)

p53 Checkpoint

(1)

Tests for Carcinogenic Potential of Chemicals

(4)

In Vivo Chronic Rodent Carcinogenesis Studies

(2)

Additional In Vivo Tests for Carcinogenicity

(2)

In Vitro Short-term Tests

(1)

Conclusion

(1)

Further Reading

(2)

Clinical Pathology

(24)

Introduction

(1)

Hematology

(6)

Parameters Generally Included in Study Protocols

(1)

Interpretative Hematology

(5)

Clinical Chemistry

(7)

Cholesterol, Triglycerides, and Glucose

(3)

Serum Proteins

(1)

Indicators of Hepatic Integrity and Function

(2)

Indicators of Renal Function

(1)

Electrolytes

(1)

Calcium and Inorganic Phosphate

(1)

Enzymes of Muscle Origin

(1)

Microsomal Enzyme Induction

(1)

Urinalysis

(1)

Interpretation of Clinical Pathology Results

(5)

Potential Effects of Factors Unrelated to Test Article Treatment

(1)

Comparators: Concurrent Controls, Reference Ranges

(1)

Statistical Analyses

(1)

Direct Versus Indirect Effects

(1)

Pharmacologic Versus Toxic Effects

(1)

Biological Importance of Treatment-related Effects

(1)

Reporting of Clinical Pathology Findings

(1)

Summary

(1)

Further Reading

(3)

Nomenclature: Terminology for Morphologic Alterations

(14)

Introduction

(1)

Basic Terminology

(1)

Terminology Issues

(9)

Training

(1)

Multiple Pathologists

(1)

Diagnostic Drift

(1)

Lesion Complexity

(1)

Standardized Nomenclature

(1)

Recording Pathology Data

(1)

Suggested Practices

(1)

Summary

(1)

Further Reading

(2)

Techniques in Toxicologic Pathology

(12)

Introduction

(1)

Factors Influencing Evaluation of Altered Morphology

(9)

Factors in Collection and Processing of Tissue

(3)

Factors Intrinsic to the Animal

(3)

Factors Related to the Environment

(1)

Factors Related to Nomenclature

(1)

Further Reading

(2)

Respiratory System

(42)

Introduction

(1)

Structure and Cell Biology

(10)

Macroscopic and Microscopic Anatomy

(6)

Physiology and Functional Considerations

100

(2)

Xenobiotic Exposure, Metabolism, and Excretion

102

(2)

Mechanisms of Toxicity

104

(5)

Direct Toxicity

105

(1)

Metabolic Activation

105

(1)

Immune-mediated Toxicity

106

(2)

Toxicity and Responses to Inhaled Particles

108

(1)

Xenobiotic Interactions

109

(1)

Modifying Factors in Toxicity

109

(1)

Response to Injury

109

(19)

Injury, Regeneration, and Repair

110

(1)

Nasopharyngeal and Laryngeal Responses to Injury

111

(2)

Airway Response to Injury

113

(5)

Pulmonary Parenchymal Response to Injury

118

(1)

Edema

119

(2)

Inflammation

121

(3)

Fibrosis

124

(2)

Emphysema

126

(1)

Neoplasia

127

(1)

Evaluation of Toxicity

128

(5)

Methods for Testing

129

(1)

Pulmonary Function

130

(1)

Bronchopulmonary Lavage

130

(1)

Biochemical Evaluation

131

(1)

Morphologic Evaluation

131

(2)

Conclusions

133

(1)

Further Reading

133

(2)

Skin and Oral Mucosa

135

(28)

Skin

135

(6)

Introduction

135

(1)

Structure and Function of Skin

136

(1)

Microscopic Anatomy

136

(2)

Skin Cell Subpopulations

138

(1)

Physiology and Biochemistry

138

(3)

Comparative Mechanisms of Cutaneous Toxicity

141

(6)

Direct Damage

141

(3)

Immunomediated Cutaneous Toxicity

144

(2)

Phototoxicity and Photoallergy

146

(1)

Response of Skin to Injury

147

(9)

Fundamental Non-neoplastic Lesions

147

(8)

Neoplastic Lesions

155

(1)

Evaluation of Cutaneous Toxicity

156

(3)

Skin Irritation Tests

157

(1)

Carcinogenesis Bioassays

157

(1)

Morphologic Assessment

158

(1)

Other Bioassays

158

(1)

Transgenic Animal Models

158

(1)

In Vitro Testing

159

(1)

Oral Mucosa

159

(2)

Introduction

159

(1)

Structure and Function of the Oral Mucosa

159

(1)

Microscopic Anatomy

159

(1)

Physiology

159

(1)

Comparative Mechanisms of Mucosal Toxicity

160

(1)

Response of Oral Mucosa to Injury

160

(1)

Fundamental Non-neoplastic Lesions

160

(1)

Carcinogenesis

161

(1)

Evaluation of Oral Toxicity

161

(1)

Further Reading

161

(2)

Gastrointestinal Tract

163

(34)

Introduction

163

(1)

Structure and Function of the Gastrointestinal Tract

164

(11)

Macroscopic and Microscopic Structure and Function

164

(7)

Enteric Lymphoid System

171

(1)

Enteric Nervous System

172

(1)

Biotransformation

172

(2)

Bacterial Metabolism

174

(1)

Enterohepatic Circulation

174

(1)

Comparative Mechanisms of Gastrointestinal Toxicity

175

(9)

Intestinal Barrier Function

175

(2)

Intestinal Malabsorption

177

(1)

Altered Blood Supply

177

(1)

Mucosal Barrier Damage and Cytotoxicity

178

(3)

Hypersensitivity

181

(2)

Neurotransmitter Effects

183

(1)

Perturbation of Microflora

183

(1)

Carcinogenicity

183

(1)

Response of the Gastrointestinal Tract to Injury

184

(7)

Pathophysiological Responses

184

(2)

Inflammatory Response

186

(1)

Mucosal Response

187

(2)

Organ-specific Responses

189

(2)

Evaluation of Gastrointestinal Toxicity

191

(5)

In Vitro Strategies

191

(1)

In Vivo Strategies

192

(1)

Molecular Pathology

192

(1)

Morphologic Methods

193

(1)

Animal Models

194

(2)

Further Reading

196

(1)

The Liver

197

(40)

Introduction

197

(1)

Structure and Function

197

(3)

Gross and Microscopic Anatomy

198

(1)

Cell Components

198

(2)

Xenobiotic Metabolism

200

(1)

Mechanisms of Toxicity

200

(2)

Classification of Hepatoxicants

201

(1)

Cellular Mechanisms of Toxicity

201

(1)

Non-neoplastic Responses to Injury

202

(26)

Histologic Types of Hepatic Necrosis

208

(6)

Intracellular Accumulations

214

(4)

Pathology of Transcription and Translation

218

(1)

Cholestasis

219

(1)

Hepatocellular Adaptive Responses

219

(1)

Hepatocellular Proliferation

220

(1)

Bile Ductular Lesions

221

(3)

Nonparenchymal Cell Toxicity

224

(1)

Hepatitis

225

(1)

Hepatic Fibrosis and Cirrhosis

226

(2)

Hepatic Neoplasia

228

(1)

Hepatocellular Neoplasia

228

(3)

Bile Duct Neoplasms

230

(1)

Endothelial Neoplasms

231

(1)

Kupffer Cell Neoplasms

231

(1)

Evaluation of Toxicity

231

(4)

Morphologic Evaluation

232

(1)

Clinical Chemistry Evaluation

232

(2)

Noninvasive Imaging

234

(1)

In Vitro Approaches

234

(1)

Use of Animals as Models

234

(1)

Summary and Conclusions

235

(1)

Further Reading

235

(2)

Pancreas

237

(24)

Exocrine Pancreas

237

(1)

Introduction

237

(1)

Normal Structure of Exocrine Pancreas

238

(2)

Gross Anatomy

238

(1)

Microscopic Anatomy and Ultrastructure

238

(2)

Physiology of Exocrine Pancreas

240

(1)

Comparative Mechanisms of Exocrine Pancreatic Toxicity

241

(2)

Response of Exocrine Pancreas to Injury

243

(5)

Cytotoxic Effects on Acinar Cells

243

(4)

Cytotoxic Effects in Ductal and Centroacinar Cells

247

(1)

Carcinogenesis

247

(1)

Evaluation of Exocrine Pancreatic Toxicity

248

(2)

Methods of Testing

249

(1)

Morphologic Evaluation of Toxicity

250

(1)

Animal Models

250

(1)

Summary and Conclusions

250

(1)

Endocrine Pancreas

251

(1)

Structure of Endocrine Pancreas

251

(1)

Gross Anatomy

251

(1)

Microscopic Anatomy and Ultrastructure

251

(1)

Physiology of Endocrine Pancreas

252

(1)

Mechanisms of Endocrine Pancreatic Toxicity

253

(3)

Insulin-dependent Diabetes Mellitus

253

(1)

Non-insulin-dependent Diabetes Mellitus

254

(1)

Glucose Intolerance

255

(1)

Response of Endocrine Pancreas to Injury

256

(2)

Apoptosis

256

(1)

Necrosis

256

(1)

Insulitis

257

(1)

Regeneration

258

(1)

Carcinogenesis

258

(1)

Evaluation of Endocrine Pancreatic Toxicity

258

(1)

In Vivo Testing

258

(1)

In Vitro Testing

258

(1)

Animal Models

258

(1)

Summary and Conclusions

258

(1)

Further Reading

259

(2)

Kidney and Lower Urinary Tract

261

(58)

Introduction

261

(1)

Renal Structure and Function

262

(11)

Gross, Microscopic, and Ultrastructural Anatomy

262

(7)

Physiology

269

(4)

Mechanisms of Toxicity

273

(30)

Overview and Classification

273

(2)

Glomerular Injury

275

(9)

Proximal Tubular Injury

284

(12)

Other Sites of Renal Injury

296

(3)

Lower Urinary Tract

299

(1)

Renal Carcinogenesis

300

(3)

Lower Urinary Tract Carcinogenesis

303

(1)

Response to Injury

303

(11)

Introduction

303

(1)

Glomerulus

303

(1)

Proximal Tubule and Interstitium

304

(5)

Renal Papillary Necrosis

309

(1)

Renal Tubular Hyperplasia and Neoplasia

309

(1)

Lower Urinary Tract: Non-neoplastic Lesions

310

(3)

Lower Urinary Tract Epithelial Neoplasms

313

(1)

Evaluation of Toxicity

314

(3)

Diagnostic Evaluation of Renal Disease

314

(1)

Routine Screening for Nephrotoxicity

314

(1)

Special Techniques

315

(1)

Evaluation of the Lower Urinary Tract

316

(1)

Conclusion

317

(1)

Further Reading

317

(2)

Cardiovascular and Skeletal Muscle Systems

319

(58)

Heart

320

(1)

Introduction

320

(1)

Structure and Function

320

(4)

Gross and Microscopic Anatomy

320

(1)

Cellular and Extracellular Elements of the Heart: Biology and Clinical Relevance

321

(2)

Physiology and Functional Considerations

323

(1)

Xenobiotic Exposure

324

(1)

Mechanisms of Toxicity

324

(7)

Physiological Mechanisms of Functional Alterations

324

(4)

Biochemical Mechanisms of Cardiotoxicosis

328

(1)

Cardiotoxicoses Due to Direct Cellular Injury

329

(1)

Cardiotoxicoses Due to Indirect Acting Injury

329

(1)

Organellar Localization of Injury

330

(1)

Xenobiotic Interactions

331

(1)

Response to Injury

331

(15)

Developmental Cardiotoxicities

334

(1)

Myocardium

335

(11)

Endocardium

346

(1)

Pericardium

346

(1)

Valves

346

(1)

Evaluation of Cardiotoxicity

346

(5)

Physiologic Evaluation of Toxicity

347

(2)

Morphologic Evaluation of Toxicity

349

(2)

Biochemical Evaluation of Toxicity

351

(1)

Use of Animals as Models

351

(1)

Vessels

351

(1)

Introduction

351

(1)

Structure and Function

352

(3)

Microscopic Anatomy

352

(1)

Physiology and Functional Considerations

352

(3)

Mechanisms of Toxicity

355

(2)

Vasculotoxic Effects of Xenobiotics

355

(1)

Vascular Toxicity in Specific Organs

356

(1)

Response to Injury

357

(6)

Regeneration and Repair

358

(1)

Vessel Alterations

358

(5)

Evaluation of Vasotoxic Effects

363

(2)

Physiologic Methods for Testing

363

(1)

Morphologic Evaluation

364

(1)

Use of Animals as Models

364

(1)

Skeletal Muscle

365

(1)

Introduction

365

(1)

Structure and Function

365

(2)

Gross and Microscopic Anatomy

365

(1)

Cells of Skeletal Muscle: Biology and Clinical Relevance

365

(2)

Physiologic and Functional Considerations

367

(1)

Mechanisms of Toxicity

367

(3)

Altered Neurogenic Function

367

(1)

Altered Immunologic Function

368

(1)

Localized Damage

368

(1)

Cell Membrane Alterations

368

(1)

Sarcoplasmic Reticulum Alterations

369

(1)

Microtubular Alterations

369

(1)

Myofilament Alterations

369

(1)

Lysosomal Alterations

369

(1)

Altered Intracellular Calcium Concentration

369

(1)

Altered Protein Synthesis

369

(1)

Altered Muscle Cell Differentiation

370

(1)

Response to Injury

370

(3)

Injury, Regeneration, and Repair

370

(1)

Skeletal Muscle Alterations

371

(2)

Evaluation of Skeletal Muscle Toxicity

373

(3)

Methods for Testing

374

(1)

Morphologic Evaluation

374

(2)

Use of Animals as Models

376

(1)

Further Reading

376

(1)

Nervous System

377

(34)

Introduction

377

(1)

Structure and Function

378

(9)

Macroscopic Structure

378

(1)

Microscopic Anatomy

379

(2)

Specialized Anatomical Features

381

(1)

Select Functions and Neurotoxicity

382

(5)

Mechanisms of Disease and Classification of Neurotoxic Diseases

387

(18)

Neuronopathies

387

(9)

Axonopathies

396

(2)

Myelinopathies

398

(2)

Toxicants Affecting Vascular Integrity

400

(4)

Developmental Neurotoxicants

404

(1)

Neurocarcinogens

405

(1)

Evaluation of Neurotoxicity

405

(4)

Use of Animals as Models

405

(1)

Tests of Nervous System Function

405

(1)

Morphologic Evaluation

406

(3)

In Vitro Systems

409

(1)

Conclusions

409

(1)

Further Reading

410

(1)

Bones and Joints

411

(40)

Introduction

411

(1)

Skeletal Structure and Composition

412

(5)

Formation and Development

412

(4)

Composition of Bone

416

(1)

Species Differences in Composition and Changes with Age

416

(1)

Bone Physiology and Function

417

(3)

Modeling and Remodeling of Bone

417

(1)

Biomechanics

417

(1)

Mineral Homeostasis

418

(1)

Regulation of Bone Cell Function

418

(2)

Mechanisms of Toxicity

420

(8)

Bone Toxicity

420

(6)

Joint Toxicity

426

(2)

Response of the Skeleton to Toxic Injury

428

(14)

Bone

428

(10)

Joints

438

(4)

Evaluation of Skeletal Toxicity

442

(6)

Testing for Skeletal Toxicity

442

(1)

Morphologic Evaluation

443

(4)

Biochemical Evaluation

447

(1)

Animal Models of Skeletal Disease

448

(1)

Summary

448

(1)

Further Reading

449

(2)

Immune System

451

(40)

Introduction

451

(1)

Function and Structure of the Immune System

451

(16)

Function of the Immune System

451

(5)

Structure of the Immune System

456

(11)

Comparative Mechanisms of Immune Toxicity

467

(10)

Introduction

467

(1)

Examples of Immunotoxic Agents

468

(9)

Response of the Immune System to Toxic Injury

477

(9)

Decreased Cellularity

478

(6)

Increased Cellularity

484

(1)

Neoplasia

484

(1)

Inflammation in Nonlymphoid Tissues

485

(1)

Testing for Immunotoxicity

486

(3)

In Vivo and In Vitro Approaches

486

(1)

Morphologic Techniques

487

(1)

Animal Models

488

(1)

Summary

489

(1)

Further Reading

489

(2)

Hematopoietic System

491

(22)

Introduction

491

(1)

Phylogeny

491

(1)

Ontogeny

492

(1)

Structure and Function

492

(4)

Gross and Microscopic Anatomy

492

(2)

Hematopoiesis

494

(1)

Cellular Kinetics

495

(1)

Comparative Mechanisms of Toxicity

496

(7)

Idiosyncratic Reactions

496

(3)

Direct Damage

499

(2)

Myelotoxicity

501

(2)

Responses of Hematopoietic Tissues to Toxic Injury

503

(7)

Changes in Blood

503

(2)

Changes in Bone Marrow

505

(5)

Hematopoietic Assessment

510

(2)

Summary

512

(1)

Further Reading

512

(1)

Endocrine System

513

(40)

Introduction

513

(1)

Adrenal Cortex

513

(10)

Structure and Function

513

(3)

Mechanisms of Toxicity

516

(1)

Response to Injury

516

(7)

Evaluation of Toxicity

523

(1)

Adrenal Medulla

523

(2)

Structure and Function

523

(1)

Mechanisms of Toxicity

523

(1)

Response to Injury

523

(2)

Evaluation of Toxicity

525

(1)

Pituitary Gland

525

(5)

Structure and Function

525

(2)

Mechanisms of Toxicity

527

(1)

Response to Injury

527

(3)

Evaluation of Toxicity

530

(1)

Thyroid C-cells

530

(2)

Structure and Function

530

(1)

Mechanisms of Toxicity

531

(1)

Response to Injury

531

(1)

Thyroid Follicular Cells

532

(11)

Structure and Function

532

(4)

Mechanisms of Toxicity

536

(2)

Response to Injury

538

(5)

Evaluation of Toxicity

543

(1)

Parathyroid Gland

543

(7)

Introduction

543

(1)

Structure and Function

544

(2)

Mechanisms of Toxicity

546

(1)

Response of Parathyroid Chief Cells to Injury

547

(3)

Evaluation of Toxicity

550

(1)

Further Reading

550

(3)

Male Reproductive System

553

(46)

Introduction

553

(1)

Structure and Cell Biology

554

(15)

Embryological Derivation of the Reproductive Tract

554

(1)

Structure of the Testes

554

(4)

Physiology and Functional Considerations of the Testis

558

(8)

Structure and Function of the Epididymis and Excurrent Ducts

566

(2)

Structure and Function of Accessory Sex Organs

568

(1)

Penis and Ejaculation

569

(1)

Mechanisms of Toxicity

569

(10)

Role of Metabolism

570

(1)

Cell-specific Toxicity in the Testis

571

(2)

Vascular Effects and Indirect Toxicity to the Testis

573

(2)

Epididymal and Sperm Toxicity

575

(1)

Secondary Sex Organs

576

(1)

Hormone Disruption

576

(1)

Toxicity to the Developing Reproductive Tract

577

(2)

Responses to Injury

579

(14)

Disruption of Spermatogenesis

580

(3)

Tubular Dilatation and Tubular Shrinkage

583

(1)

Tubular and Testicular Necrosis

583

(2)

Leydig Cell Response

585

(1)

Disruption of Sperm Maturation

585

(1)

Epididymal Response

586

(1)

Response to Alterations in Hormone Balance

586

(3)

Reversibility

589

(1)

Reproductive Toxicity in Domestic Animals

590

(3)

Evaluation of Toxicity

593

(3)

Detecting Toxicity

593

(1)

Characterization of Reproductive Toxicity

593

(2)

Functional Characterization

595

(1)

Testing for Toxicity of the Developing Reproductive Tract

596

(1)

Conclusions

596

(1)

Further Reading

597

(2)

Female Reproductive System

599

(34)

Introduction

599

(1)

Structure and Functional Physiology

600

(9)

Structure

600

(6)

Functional Physiology

606

(3)

Mechanisms of Toxicity

609

(6)

General Toxicity

609

(1)

Ovary, Uterus, and Vagina as a Unit

609

(4)

Local Vaginal Toxicity

613

(1)

Carcinogenesis

613

(2)

Response to Injury

615

(13)

General Responses: Ovary, Uterus, and Vagina as a Unit

615

(5)

Local Vaginal Responses

620

(2)

Reproductive Toxicity in Domestic Animals

622

(3)

Neoplasia

625

(3)

Testing for Toxicity

628

(2)

General Toxicity

628

(2)

Local Vaginal Toxicity

630

(1)

Summary

630

(1)

Further Reading

630

(3)

Developmental Pathology

633

(40)

Introduction

633

(1)

Overview of Fetal Toxicologic Pathology

633

(1)

Basic Principles of Developmental Toxicology

634

Incidence of Congenital Anomalies

534

(100)

Normal Morphologic Development

634

(4)

Fertilization and Blastocyst Formation

635

(1)

Gastrulation

635

(1)

Organogenesis

635

(2)

Histogenesis and Functional Maturation

637

(1)

Mechanisms of Toxicity

638

(4)

Critical Phases of Intrauterine Development

638

(1)

Modifying Factors

639

(3)

Response to Injury

642

(6)

Death

642

(1)

Malformations

643

(3)

Intrauterine Growth Retardation

646

(1)

Perinatal Toxicology

646

(1)

Endocrine Disruption

647

(1)

Congenital Neoplasia

647

(1)

How Dose Relates to Manifestation of Abnormal Development

648

(1)

Selected Malformations

648

(12)

Central Nervous System

648

(5)

Craniofacial Structures

653

(2)

Cardiovascular System

655

(1)

Respiratory System

656

(1)

Gastrointestinal System

656

(1)

Urinary System

656

(1)

Reproductive System

657

(1)

Skeletal System

658

(2)

Developmental Toxicity Testing and Risk Assessment

660

(5)

Hazard Identification and Dose-response Analysis

660

(4)

Dose-Response Evaluation

664

(1)

Field Investigation of Anomalies in Domestic Animals

665

(3)

Defining the Individual Incident

665

(1)

Defining the Prevalence

666

(1)

Defining the Maternal Environment

666

(1)

Genetic Analysis

667

(1)

Environmental Analysis: An Epidemiological Approach

667

(1)

Further Reading

668

(1)

Glossary

669

(4)

Index

673

Matthew A. Wallig, DVM, Ph.D., DACVP, is Professor Emeritus in the Department of Pathobiology, College of Veterinary Medicine, the Department of Food Science and Human Nutrition, as well as the Division of Nutritional Sciences at the University of Illinois. His research has focused on the chemoprotective properties and mechanisms of phytochemicals in the diet, in particular those in cruciferous vegetables, soy, and tomatoes. His current interests have expanded to include defining morphologic parameters for diagnostic quantitative ultrasound in pancreatitis, pancreatic and hepatic neoplasia, metastatic disease, and chronic hepatic diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Matt has served as an Editor for the last two editions of the Fundamentals of Toxicologic Pathology and Haschek and Rousseauxs Handbook of Toxicologic Pathology. Professor Haschek-Hock has served as president of the Society of Toxicologic Pathology and the Society of Toxicologys Comparative and Veterinary Specialty Section, as well as Councilor of the American College of Veterinary Pathologists, board member of the American Board of Toxicology; as Associate Editor for Toxicological Sciences and for Toxicologic Pathology; as Editorial Board member for Fundamental and Applied Toxicology, Veterinary Pathology and Toxicologic Pathology. She has served as a member on the USFDA Veterinary Medicine Advisory Committee for the Center for Veterinary Medicine, the EPAs FIFRA Science Advisory Panel, and National Academy of Sciences Committee. She currently serves on the Board of Directors of the C.L. Davis Foundation for the Advancement of Veterinary and Comparative Pathology. She was awarded the Society of Toxicologic Pathologys Achievement Award in 2007 and the Midwest Regional Chapter Society of Toxicologys Kenneth DuBois Award in 2011. Colin G. Rousseaux, BVSc, Ph.D., DABT, FIATP, is also a Fellow of the Royal College of Pathology (FRCPath) and Fellow of the Academy of Toxicological Sciences (FATS). He is a Professor (Adjunct) in the Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Canada. He has over 35 years of experience in comparative and toxicologic pathology with a research focus on herbal remedies, fetal development and teratology, and environmental pollutants. He has described, investigated, and evaluated numerous toxicologic pathology issues associated with pharmaceuticals, pesticides, and agrochemicals. He has served on the editorial board of Toxicologic Pathology. He is a former President of the STP. Colin served as an Editor for the three editions of the Fundamentals of Toxicologic Pathology and Haschek and Rousseauxs Handbook of Toxicologic Pathology.

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