PREFACE TO THE FOURTH EDITION xxi
CONTRIBUTORS xxiii
PART I INTRODUCTION 1
1. Introduction to Toxicology 3
Ernest Hodgson
1.1 Definition and Scope 3
1.2 Relationship to Other Sciences 9
1.3 A Brief History of Toxicology 10
1.4 Dose–Response Relationships 11
1.5 Sources of Toxic Compounds 12
1.6 Movement of Toxicants in the Environment 12
Bibliography and Suggested Reading 13
Sample Questions 14
2. Introduction to Biochemical and Molecular Methods in Toxicology 15
Ernest Hodgson, Gerald A. Leblanc, Sharon A. Meyer, and Robert C. Smart
2.1 Introduction 15
2.2 Cell Culture Techniques 15
2.3 Molecular Techniques 19
2.4 Immunochemical Techniques 23
2.5 Proteomics 26
2.6 Metabolomics 26
2.7 Bioinformatics 26
2.8 Summary and Conclusions 27
Bibliography and Suggested Reading 27
Sample Questions 27
PART II CLASSES OF TOXICANTS 29
3. Exposure Classes, Toxicants in Air, Water, Soil, Domestic, and Occupational Settings 31
W. Gregory Cope
3.1 Air Pollutants 31
3.2 Water and Soil Pollutants 38
3.3 Occupational Toxicants 42
Bibliography and Suggested Reading 46
Air Pollutants 46
Water and Soil Pollutants 47
Occupational Toxicants 47
Sample Questions 47
4. Classes of Toxicants: Use Classes 49
W. Gregory Cope and Ernest Hodgson
4.1 Introduction 49
4.2 Metals 49
4.3 Agricultural Chemicals (Pesticides) 55
4.4 Food Additives and Contaminants 65
4.5 Toxins 66
4.6 Solvents 71
4.7 Therapeutic Drugs 71
4.8 Drugs of Abuse 72
4.9 Combustion Products 72
4.10 Cosmetics 74
Bibliography and Suggested Reading 74
General 74
Metals 74
Pesticides 75
Toxins 75
Solvents 75
Therapeutic Drugs 75
Sample Questions 75
PART III TOXICANT PROCESSING IN VIVO 77
5. Absorption and Distribution of Toxicants 79
Ronald E. Baynes and Ernest Hodgson
5.1 Introduction 79
5.2 Cell Membranes 80
5.3 Mechanisms of Transport 82
5.4 Physicochemical Properties Relevant to Diffusion 87
5.5 Routes of Absorption 90
5.6 Toxicant Distribution 99
5.7 Toxicokinetics 108
Bibliography and Suggested Reading 112
Sample Questions 113
6. Metabolism of Toxicants 115
Ernest Hodgson and Randy L. Rose
6.1 Introduction 115
6.2 Phase I Reactions 116
6.3 Phase II Reactions 143
Bibliography and Suggested Reading 154
Sample Questions 155
7. Reactive Metabolites 157
Ernest Hodgson and Randy L. Rose
7.1 Introduction 157
7.2 Activation Enzymes 158
7.3 Nature and Stability of Reactive Metabolites 160
7.4 Fate of Reactive Metabolites 161
7.5 Factors Affecting Toxicity of Reactive Metabolites 162
7.6 Reactive Oxygen Species 163
7.7 Examples of Activating Reactions 164
7.8 Summary and Conclusions 170
Bibliography and Suggested Reading 171
Sample Questions 171
8. Chemical and Physiological Effects on Xenobiotic Metabolism 173
Andrew D. Wallace and Ernest Hodgson
8.1 Introduction 173
8.2 Nutritional Effects 173
8.3 Physiological Effects 176
8.4 Comparative and Genetic Effects 182
8.5 Chemical Effects 191
8.6 Environmental Effects 207
8.7 Summary and Conclusions 209
Bibliography and Suggested Reading 210
Sample Questions 211
9. Elimination of Toxicants 213
Gerald A. Leblanc
9.1 Introduction 213
9.2 Transport 215
9.3 Renal Elimination 216
9.4 Hepatic Elimination 217
9.5 Respiratory Elimination 220
9.6 Conclusion 221
Bibliography and Suggested Reading 221
Sample Questions 222
PART IV TOXIC ACTION 223
10. Acute Toxicity 225
Gerald A. Leblanc
10.1 Introduction 225
10.2 Acute Exposure and Effect 225
10.3 Dose–Response Relationships 227
10.4 Nonconventional Dose–Response Relationships 229
10.5 Alternative Methods 230
10.6 Mechanisms of Acute Toxicity 231
Bibliography and Suggested Reading 236
Sample Questions 236
11. Chemical Carcinogenesis and Mutagenesis 237
Robert C. Smart
11.1 DNA Damage and Mutagenesis 237
11.2 General Aspects of Cancer 239
11.3 Human Cancer 242
11.4 Classes of Agents That Are Associated with Carcinogenesis 251
11.5 General Aspects of Chemical Carcinogenesis 254
11.6 Oncogenes 259
11.7 Tumor Suppressor Genes 262
Bibliography and Suggested Reading 264
Sample Questions 264
12. Teratogenesis 265
Jill A. Barnes and Ida M. Washington
12.1 Introduction 265
12.2 Overview of Embryonic Development 266
12.3 Principles of Teratogenesis 268
12.4 Mechanisms of Teratogenesis 268
12.5 Future Considerations 272
Bibliography and Suggested Reading 272
Sample Questions 272
PART V ORGAN TOXICITY 275
13. Hepatotoxicity 277
Andrew D. Wallace and Sharon A. Meyer
13.1 Introduction 277
13.2 Susceptibility of the Liver 279
13.3 Types of Liver Injury 279
13.4 Mechanisms of Hepatotoxicity 283
13.5 Examples of Hepatotoxicants 285
13.6 Metabolic Activation of Hepatotoxicants 288
Bibliography and Suggested Reading 289
Sample Questions 289
14. Nephrotoxicity 291
Joan B. Tarloff and Andrew D. Wallace
14.1 Introduction 291
14.2 Factors Contributing to Nephrotoxicity 292
14.3 Examples of Nephrotoxicants 293
14.4 Summary 301
Bibliography and Suggested Reading 301
Sample Questions 302
15. Toxicology of the Nervous System 303
Bonita L. Blake
15.1 Introduction 303
15.2 The Nervous System 303
15.3 Toxicant Effects on the Nervous System 312
15.4 Neurotoxicity Testing 317
15.5 Summary 321
Bibliography and Suggested Reading 322
Sample Questions 322
16. Reproductive System 323
Heather Patisaul
16.1 Introduction 323
16.2 The Hypothalamic-Pituitary-Gonadal Axis 324
16.3 Male Reproductive Physiology 326
16.4 Disruption of Male Reproduction By Toxicants 330
16.5 Female Reproductive Physiology 332
16.6 Disruption of Female Reproduction by Toxicants 335
16.7 Summary 341
Bibliography and Suggested Reading 341
Sample Questions 343
17. Endocrine Toxicology 345
Gerald A. Leblanc
17.1 Introduction 345
17.2 Endocrine System 345
17.3 Endocrine Disruption 352
17.4 Incidents of Endocrine Toxicity 358
17.5 Conclusion 361
Bibliography and Suggested Reading 362
Sample Questions 362
18. Respiratory Toxicology 363
James C. Bonner
18.1 Introduction 363
18.2 Anatomy and Function of the Respiratory Tract 363
18.3 Toxicant-Induced Lung Injury, Remodeling, and Repair 373
18.4 Occupational and Environmental Lung Diseases 380
Bibliography and Suggested Reading 385
Sample Questions 385
19. Immune System 387
MaryJane K. Selgrade
19.1 Introduction 387
19.2 The Immune System 388
19.3 Immune Suppression 391
19.4 Classification of Immune-Mediated Injury (Hypersensitivity) 396
19.5 Effects of Chemicals on Allergic Disease 398
19.6 Other Issues: Autoimmunity and the Developing
Immune System 403
Bibliography and Suggested Reading 404
Sample Questions 404
PART VI APPLIED TOXICOLOGY 407
20. Toxicity Testing 409
Ernest Hodgson and Helen Cunny
20.1 Introduction 409
20.2 Experimental Administration of Toxicants 412
20.3 Chemical and Physical Properties 414
20.4 Exposure and Environmental Fate 414
20.5 In Vivo Tests 415
20.6 In Vitro and Other Short-Term Tests 442
20.7 Ecological Effects 451
20.8 Risk Analysis 453
20.9 The Future of Toxicity Testing 453
Bibliography and Suggested Reading 454
Sample Questions 455
21. Forensic and Clinical Toxicology 457
Sharon A. Meyer and Bonita L. Blake
21.1 Introduction 457
21.2 Forensic Toxicology 457
21.3 Clinical Toxicology 462
21.4 Analytical Methods in Forensic and Clinical Toxicology 469
Bibliography and Suggested Reading 472
Sample Questions 473
22. Prevention of Toxicity 475
Ernest Hodgson
22.1 Introduction 475
22.2 Legislation and Regulation 475
22.3 Prevention in Different Environments 482
22.4 Education 485
Bibliography and Suggested Reading 486
Sample Questions 487
23. Human Health Risk Assessment 489
Ronald E. Baynes
23.1 Introduction 489
23.2 Risk Assessment Methods 490
23.3 Noncancer Risk Assessment 493
23.4 Cancer Risk Assessment 500
23.5 PBPK Modeling 503
Bibliography and Suggested Reading 504
Sample Questions 505
PART VII ENVIRONMENTAL TOXICOLOGY 507
24. Toxicant Analysis: Analytical Methods and Quality Assurance 509
Chris Hofelt
24.1 Introduction 509
24.2 Environmental Sample Collection Methods 510
24.3 Analytical Techniques 514
24.4 Quantifi cation, QA, and QC 525
24.5 Summary 528
Bibliography and Suggested Reading 528
Sample Questions 529
25. Basics of Environmental Toxicology 531
Gerald A. Leblanc and David B. Buchwalter
25.1 Introduction 531
25.2 Environmental Persistence 532
25.3 Bioaccumulation 535
25.4 Toxicity 539
25.5 Conclusion 546
Bibliography and Suggested Reading 547
Sample Questions 547
26. Transport and Fate of Toxicants in the Environment 549
Damian Shea
26.1 Introduction 549
26.2 Sources of Toxicants to the Environment 550
26.3 Transport Processes 553
26.4 Equilibrium Partitioning 557
26.5 Transformation Processes 560
26.6 Environmental Fate Models 567
Bibliography and Suggested Reading 569
Sample Questions 569
27. Environmental Risk Assessment 571
Damian Shea
27.1 Introduction 571
27.2 Formulating the Problem 573
27.3 Analyzing Exposure and Effects Information 578
27.4 Characterizing Risk 582
27.5 Managing Risk 587
Bibliography and Suggested Reading 588
Sample Questions 589
PART VIII NEW APPROACHES IN TOXICOLOGY 591
28. Perspectives on Informatics in Toxicology 593
Seth W. Kullman, Carolyn J. Mattingly, Joel N. Meyer, and Andrew Whitehead
28.1 Introduction 593
28.2 Transcriptomics 594
28.3 Annotation Resources 595
28.4 Genome Sequencing, Resequencing and Genotyping 597
28.5 Epigenomic Profi ling 598
28.6 Computational Toxicology 599
28.7 Informatics Tools in Toxicology 601
Bibliography and Suggested Reading 602
Sample Question 605
29. Future Considerations 607
Ernest Hodgson
29.1 Introduction 607
29.2 Risk Assessment 609
29.3 Risk Management 613
29.4 Risk Communication 613
29.5 In Vivo Toxicity 614
29.6 In Vitro Toxicity 614
29.7 Molecular and Biochemical Toxicology 614
29.8 Development of Selective Toxicants 615
29.9 Summary and Conclusions 616
Bibliography and Suggested Reading 616
Sample Questions 617
GLOSSARY 619
INDEX 638
