"The book assumes a good knowledge of general toxicology and some knowledge of specialist areas, and would be a useful aid if studying for a higher degree where basic understanding has been." (British Toxicology Society, Winter 2010)

ERNEST HODGSON, PhD, is Distinguished Professor Emeritus of Toxicology at North Carolina State University. In addition to the previous editions of A Textbook of Modern Toxicology, he coedited Molecular and Biochemical Toxicology, Fourth Edition (Wiley) and its prior editions. Dr. Hodgson is the Editor of the Journal of Biochemical and Molecular Toxicology.

pPREFACE TO THE FOURTH EDITION xxi pCONTRIBUTORS xxiii pPART I INTRODUCTION 1 p1. Introduction to Toxicology 3 Ernest Hodgson p1.1 Definition and Scope 3 p1.2 Relationship to Other Sciences 9 p1.3 A Brief History of Toxicology 10 p1.4 Dose Response Relationships 11 p1.5 Sources of Toxic Compounds 12 p1.6 Movement of Toxicants in the Environment 12 pBibliography and Suggested Reading 13 pSample Questions 14 p2. Introduction to Biochemical and Molecular Methods in Toxicology 15 Ernest Hodgson, Gerald A. Leblanc, Sharon A. Meyer, and Robert C. Smart p2.1 Introduction 15 p2.2 Cell Culture Techniques 15 p2.3 Molecular Techniques 19 p2.4 Immunochemical Techniques 23 p2.5 Proteomics 26 p2.6 Metabolomics 26 p2.7 Bioinformatics 26 p2.8 Summary and Conclusions 27 pBibliography and Suggested Reading 27 pSample Questions 27 pPART II CLASSES OF TOXICANTS 29 p3. Exposure Classes, Toxicants in Air, Water, Soil, Domestic, and Occupational Settings 31 W. Gregory Cope p3.1 Air Pollutants 31 p3.2 Water and Soil Pollutants 38 p3.3 Occupational Toxicants 42 pBibliography and Suggested Reading 46 pAir Pollutants 46 pWater and Soil Pollutants 47 pOccupational Toxicants 47 pSample Questions 47 p4. Classes of Toxicants: Use Classes 49 W. Gregory Cope and Ernest Hodgson p4.1 Introduction 49 p4.2 Metals 49 p4.3 Agricultural Chemicals (Pesticides) 55 p4.4 Food Additives and Contaminants 65 p4.5 Toxins 66 p4.6 Solvents 71 p4.7 Therapeutic Drugs 71 p4.8 Drugs of Abuse 72 p4.9 Combustion Products 72 p4.10 Cosmetics 74 pBibliography and Suggested Reading 74 pGeneral 74 pMetals 74 pPesticides 75 pToxins 75 pSolvents 75 pTherapeutic Drugs 75 pSample Questions 75 pPART III TOXICANT PROCESSING IN VIVO 77 p5. Absorption and Distribution of Toxicants 79 Ronald E. Baynes and Ernest Hodgson p5.1 Introduction 79 p5.2 Cell Membranes 80 p5.3 Mechanisms of Transport 82 p5.4 Physicochemical Properties Relevant to Diffusion 87 p5.5 Routes of Absorption 90 p5.6 Toxicant Distribution 99 p5.7 Toxicokinetics 108 pBibliography and Suggested Reading 112 pSample Questions 113 p6. Metabolism of Toxicants 115 Ernest Hodgson and Randy L. Rose p6.1 Introduction 115 p6.2 Phase I Reactions 116 p6.3 Phase II Reactions 143 pBibliography and Suggested Reading 154 pSample Questions 155 p7. Reactive Metabolites 157 Ernest Hodgson and Randy L. Rose p7.1 Introduction 157 p7.2 Activation Enzymes 158 p7.3 Nature and Stability of Reactive Metabolites 160 p7.4 Fate of Reactive Metabolites 161 p7.5 Factors Affecting Toxicity of Reactive Metabolites 162 p7.6 Reactive Oxygen Species 163 p7.7 Examples of Activating Reactions 164 p7.8 Summary and Conclusions 170 pBibliography and Suggested Reading 171 pSample Questions 171 p8. Chemical and Physiological Effects on Xenobiotic Metabolism 173 Andrew D. Wallace and Ernest Hodgson p8.1 Introduction 173 p8.2 Nutritional Effects 173 p8.3 Physiological Effects 176 p8.4 Comparative and Genetic Effects 182 p8.5 Chemical Effects 191 p8.6 Environmental Effects 207 p8.7 Summary and Conclusions 209 pBibliography and Suggested Reading 210 pSample Questions 211 p9. Elimination of Toxicants 213 Gerald A. Leblanc p9.1 Introduction 213 p9.2 Transport 215 p9.3 Renal Elimination 216 p9.4 Hepatic Elimination 217 p9.5 Respiratory Elimination 220 p9.6 Conclusion 221 pBibliography and Suggested Reading 221 pSample Questions 222 pPART IV TOXIC ACTION 223 p10. Acute Toxicity 225 Gerald A. Leblanc p10.1 Introduction 225 p10.2 Acute Exposure and Effect 225 p10.3 Dose Response Relationships 227 p10.4 Nonconventional Dose Response Relationships 229 p10.5 Alternative Methods 230 p10.6 Mechanisms of Acute Toxicity 231 pBibliography and Suggested Reading 236 pSample Questions 236 p11. Chemical Carcinogenesis and Mutagenesis 237 Robert C. Smart p11.1 DNA Damage and Mutagenesis 237 p11.2 General Aspects of Cancer 239 p11.3 Human Cancer 242 p11.4 Classes of Agents That Are Associated with Carcinogenesis 251 p11.5 General Aspects of Chemical Carcinogenesis 254 p11.6 Oncogenes 259 p11.7 Tumor Suppressor Genes 262 pBibliography and Suggested Reading 264 pSample Questions 264 p12. Teratogenesis 265 Jill A. Barnes and Ida M. Washington p12.1 Introduction 265 p12.2 Overview of Embryonic Development 266 p12.3 Principles of Teratogenesis 268 p12.4 Mechanisms of Teratogenesis 268 p12.5 Future Considerations 272 pBibliography and Suggested Reading 272 pSample Questions 272 pPART V ORGAN TOXICITY 275 p13. Hepatotoxicity 277 Andrew D. Wallace and Sharon A. Meyer p13.1 Introduction 277 p13.2 Susceptibility of the Liver 279 p13.3 Types of Liver Injury 279 p13.4 Mechanisms of Hepatotoxicity 283 p13.5 Examples of Hepatotoxicants 285 p13.6 Metabolic Activation of Hepatotoxicants 288 pBibliography and Suggested Reading 289 pSample Questions 289 p14. Nephrotoxicity 291 Joan B. Tarloff and Andrew D. Wallace p14.1 Introduction 291 p14.2 Factors Contributing to Nephrotoxicity 292 p14.3 Examples of Nephrotoxicants 293 p14.4 Summary 301 pBibliography and Suggested Reading 301 pSample Questions 302 p15. Toxicology of the Nervous System 303 Bonita L. Blake p15.1 Introduction 303 p15.2 The Nervous System 303 p15.3 Toxicant Effects on the Nervous System 312 p15.4 Neurotoxicity Testing 317 p15.5 Summary 321 pBibliography and Suggested Reading 322 pSample Questions 322 p16. Reproductive System 323 Heather Patisaul p16.1 Introduction 323 p16.2 The Hypothalamic-Pituitary-Gonadal Axis 324 p16.3 Male Reproductive Physiology 326 p16.4 Disruption of Male Reproduction By Toxicants 330 p16.5 Female Reproductive Physiology 332 p16.6 Disruption of Female Reproduction by Toxicants 335 p16.7 Summary 341 pBibliography and Suggested Reading 341 pSample Questions 343 p17. Endocrine Toxicology 345 Gerald A. Leblanc p17.1 Introduction 345 p17.2 Endocrine System 345 p17.3 Endocrine Disruption 352 p17.4 Incidents of Endocrine Toxicity 358 p17.5 Conclusion 361 pBibliography and Suggested Reading 362 pSample Questions 362 p18. Respiratory Toxicology 363 James C. Bonner p18.1 Introduction 363 p18.2 Anatomy and Function of the Respiratory Tract 363 p18.3 Toxicant-Induced Lung Injury, Remodeling, and Repair 373 p18.4 Occupational and Environmental Lung Diseases 380 pBibliography and Suggested Reading 385 pSample Questions 385 p19. Immune System 387 MaryJane K. Selgrade p19.1 Introduction 387 p19.2 The Immune System 388 p19.3 Immune Suppression 391 p19.4 Classification of Immune-Mediated Injury (Hypersensitivity) 396 p19.5 Effects of Chemicals on Allergic Disease 398 p19.6 Other Issues: Autoimmunity and the Developing pImmune System 403 pBibliography and Suggested Reading 404 pSample Questions 404 pPART VI APPLIED TOXICOLOGY 407 p20. Toxicity Testing 409 Ernest Hodgson and Helen Cunny p20.1 Introduction 409 p20.2 Experimental Administration of Toxicants 412 p20.3 Chemical and Physical Properties 414 p20.4 Exposure and Environmental Fate 414 p20.5 In Vivo Tests 415 p20.6 In Vitro and Other Short-Term Tests 442 p20.7 Ecological Effects 451 p20.8 Risk Analysis 453 p20.9 The Future of Toxicity Testing 453 pBibliography and Suggested Reading 454 pSample Questions 455 p21. Forensic and Clinical Toxicology 457 Sharon A. Meyer and Bonita L. Blake p21.1 Introduction 457 p21.2 Forensic Toxicology 457 p21.3 Clinical Toxicology 462 p21.4 Analytical Methods in Forensic and Clinical Toxicology 469 pBibliography and Suggested Reading 472 pSample Questions 473 p22. Prevention of Toxicity 475 Ernest Hodgson p22.1 Introduction 475 p22.2 Legislation and Regulation 475 p22.3 Prevention in Different Environments 482 p22.4 Education 485 pBibliography and Suggested Reading 486 pSample Questions 487 p23. Human Health Risk Assessment 489 Ronald E. Baynes p23.1 Introduction 489 p23.2 Risk Assessment Methods 490 p23.3 Noncancer Risk Assessment 493 p23.4 Cancer Risk Assessment 500 p23.5 PBPK Modeling 503 pBibliography and Suggested Reading 504 pSample Questions 505 pPART VII ENVIRONMENTAL TOXICOLOGY 507 p24. Toxicant Analysis: Analytical Methods and Quality Assurance 509 Chris Hofelt p24.1 Introduction 509 p24.2 Environmental Sample Collection Methods 510 p24.3 Analytical Techniques 514 p24.4 Quantifi cation, QA, and QC 525 p24.5 Summary 528 pBibliography and Suggested Reading 528 pSample Questions 529 p25. Basics of Environmental Toxicology 531 Gerald A. Leblanc and David B. Buchwalter p25.1 Introduction 531 p25.2 Environmental Persistence 532 p25.3 Bioaccumulation 535 p25.4 Toxicity 539 p25.5 Conclusion 546 pBibliography and Suggested Reading 547 pSample Questions 547 p26. Transport and Fate of Toxicants in the Environment 549 Damian Shea p26.1 Introduction 549 p26.2 Sources of Toxicants to the Environment 550 p26.3 Transport Processes 553 p26.4 Equilibrium Partitioning 557 p26.5 Transformation Processes 560 p26.6 Environmental Fate Models 567 pBibliography and Suggested Reading 569 pSample Questions 569 p27. Environmental Risk Assessment 571 Damian Shea p27.1 Introduction 571 p27.2 Formulating the Problem 573 p27.3 Analyzing Exposure and Effects Information 578 p27.4 Characterizing Risk 582 p27.5 Managing Risk 587 pBibliography and Suggested Reading 588 pSample Questions 589 pPART VIII NEW APPROACHES IN TOXICOLOGY 591 p28. Perspectives on Informatics in Toxicology 593 Seth W. Kullman, Carolyn J. Mattingly, Joel N. Meyer, and Andrew Whitehead p28.1 Introduction 593 p28.2 Transcriptomics 594 p28.3 Annotation Resources 595 p28.4 Genome Sequencing, Resequencing and Genotyping 597 p28.5 Epigenomic Profi ling 598 p28.6 Computational Toxicology 599 p28.7 Informatics Tools in Toxicology 601 pBibliography and Suggested Reading 602 pSample Question 605 p29. Future Considerations 607 Ernest Hodgson p29.1 Introduction 607 p29.2 Risk Assessment 609 p29.3 Risk Management 613 p29.4 Risk Communication 613 p29.5 In Vivo Toxicity 614 p29.6 In Vitro Toxicity 614 p29.7 Molecular and Biochemical Toxicology 614 p29.8 Development of Selective Toxicants 615 p29.9 Summary and Conclusions 616 pBibliography and Suggested Reading 616 pSample Questions 617 pGLOSSARY 619 pINDEX 638