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.

"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)

• PREFACE TO THE FOURTH EDITION xxiCONTRIBUTORS xxiiiPART I INTRODUCTION 11. Introduction to Toxicology 3Ernest Hodgson1.1 Definition and Scope 31.2 Relationship to Other Sciences 91.3 A Brief History of Toxicology 101.4 Dose–Response Relationships 111.5 Sources of Toxic Compounds 121.6 Movement of Toxicants in the Environment 12Bibliography and Suggested Reading 13Sample Questions 142. Introduction to Biochemical and Molecular Methods in Toxicology 15Ernest Hodgson, Gerald A. Leblanc, Sharon A. Meyer, and Robert C. Smart2.1 Introduction 152.2 Cell Culture Techniques 152.3 Molecular Techniques 192.4 Immunochemical Techniques 232.5 Proteomics 262.6 Metabolomics 262.7 Bioinformatics 262.8 Summary and Conclusions 27Bibliography and Suggested Reading 27Sample Questions 27PART II CLASSES OF TOXICANTS 293. Exposure Classes, Toxicants in Air, Water, Soil, Domestic, and Occupational Settings 31W. Gregory Cope3.1 Air Pollutants 313.2 Water and Soil Pollutants 383.3 Occupational Toxicants 42Bibliography and Suggested Reading 46Air Pollutants 46Water and Soil Pollutants 47Occupational Toxicants 47Sample Questions 474. Classes of Toxicants: Use Classes 49W. Gregory Cope and Ernest Hodgson4.1 Introduction 494.2 Metals 494.3 Agricultural Chemicals (Pesticides) 554.4 Food Additives and Contaminants 654.5 Toxins 664.6 Solvents 714.7 Therapeutic Drugs 714.8 Drugs of Abuse 724.9 Combustion Products 724.10 Cosmetics 74Bibliography and Suggested Reading 74General 74Metals 74Pesticides 75Toxins 75Solvents 75Therapeutic Drugs 75Sample Questions 75PART III TOXICANT PROCESSING IN VIVO 775. Absorption and Distribution of Toxicants 79Ronald E. Baynes and Ernest Hodgson5.1 Introduction 795.2 Cell Membranes 805.3 Mechanisms of Transport 825.4 Physicochemical Properties Relevant to Diffusion 875.5 Routes of Absorption 905.6 Toxicant Distribution 995.7 Toxicokinetics 108Bibliography and Suggested Reading 112Sample Questions 1136. Metabolism of Toxicants 115Ernest Hodgson and Randy L. Rose6.1 Introduction 1156.2 Phase I Reactions 1166.3 Phase II Reactions 143Bibliography and Suggested Reading 154Sample Questions 1557. Reactive Metabolites 157Ernest Hodgson and Randy L. Rose7.1 Introduction 1577.2 Activation Enzymes 1587.3 Nature and Stability of Reactive Metabolites 1607.4 Fate of Reactive Metabolites 1617.5 Factors Affecting Toxicity of Reactive Metabolites 1627.6 Reactive Oxygen Species 1637.7 Examples of Activating Reactions 1647.8 Summary and Conclusions 170Bibliography and Suggested Reading 171Sample Questions 1718. Chemical and Physiological Effects on Xenobiotic Metabolism 173Andrew D. Wallace and Ernest Hodgson8.1 Introduction 1738.2 Nutritional Effects 1738.3 Physiological Effects 1768.4 Comparative and Genetic Effects 1828.5 Chemical Effects 1918.6 Environmental Effects 2078.7 Summary and Conclusions 209Bibliography and Suggested Reading 210Sample Questions 2119. Elimination of Toxicants 213Gerald A. Leblanc9.1 Introduction 2139.2 Transport 2159.3 Renal Elimination 2169.4 Hepatic Elimination 2179.5 Respiratory Elimination 2209.6 Conclusion 221Bibliography and Suggested Reading 221Sample Questions 222PART IV TOXIC ACTION 22310. Acute Toxicity 225Gerald A. Leblanc10.1 Introduction 22510.2 Acute Exposure and Effect 22510.3 Dose–Response Relationships 22710.4 Nonconventional Dose–Response Relationships 22910.5 Alternative Methods 23010.6 Mechanisms of Acute Toxicity 231Bibliography and Suggested Reading 236Sample Questions 23611. Chemical Carcinogenesis and Mutagenesis 237Robert C. Smart11.1 DNA Damage and Mutagenesis 23711.2 General Aspects of Cancer 23911.3 Human Cancer 24211.4 Classes of Agents That Are Associated with Carcinogenesis 25111.5 General Aspects of Chemical Carcinogenesis 25411.6 Oncogenes 25911.7 Tumor Suppressor Genes 262Bibliography and Suggested Reading 264Sample Questions 26412. Teratogenesis 265Jill A. Barnes and Ida M. Washington12.1 Introduction 26512.2 Overview of Embryonic Development 26612.3 Principles of Teratogenesis 26812.4 Mechanisms of Teratogenesis 26812.5 Future Considerations 272Bibliography and Suggested Reading 272Sample Questions 272PART V ORGAN TOXICITY 27513. Hepatotoxicity 277Andrew D. Wallace and Sharon A. Meyer13.1 Introduction 27713.2 Susceptibility of the Liver 27913.3 Types of Liver Injury 27913.4 Mechanisms of Hepatotoxicity 28313.5 Examples of Hepatotoxicants 28513.6 Metabolic Activation of Hepatotoxicants 288Bibliography and Suggested Reading 289Sample Questions 28914. Nephrotoxicity 291Joan B. Tarloff and Andrew D. Wallace14.1 Introduction 29114.2 Factors Contributing to Nephrotoxicity 29214.3 Examples of Nephrotoxicants 29314.4 Summary 301Bibliography and Suggested Reading 301Sample Questions 30215. Toxicology of the Nervous System 303Bonita L. Blake15.1 Introduction 30315.2 The Nervous System 30315.3 Toxicant Effects on the Nervous System 31215.4 Neurotoxicity Testing 31715.5 Summary 321Bibliography and Suggested Reading 322Sample Questions 32216. Reproductive System 323Heather Patisaul16.1 Introduction 32316.2 The Hypothalamic-Pituitary-Gonadal Axis 32416.3 Male Reproductive Physiology 32616.4 Disruption of Male Reproduction By Toxicants 33016.5 Female Reproductive Physiology 33216.6 Disruption of Female Reproduction by Toxicants 33516.7 Summary 341Bibliography and Suggested Reading 341Sample Questions 34317. Endocrine Toxicology 345Gerald A. Leblanc17.1 Introduction 34517.2 Endocrine System 34517.3 Endocrine Disruption 35217.4 Incidents of Endocrine Toxicity 35817.5 Conclusion 361Bibliography and Suggested Reading 362Sample Questions 36218. Respiratory Toxicology 363James C. Bonner18.1 Introduction 36318.2 Anatomy and Function of the Respiratory Tract 36318.3 Toxicant-Induced Lung Injury, Remodeling, and Repair 37318.4 Occupational and Environmental Lung Diseases 380Bibliography and Suggested Reading 385Sample Questions 38519. Immune System 387MaryJane K. Selgrade19.1 Introduction 38719.2 The Immune System 38819.3 Immune Suppression 39119.4 Classification of Immune-Mediated Injury (Hypersensitivity) 39619.5 Effects of Chemicals on Allergic Disease 39819.6 Other Issues: Autoimmunity and the DevelopingImmune System 403Bibliography and Suggested Reading 404Sample Questions 404PART VI APPLIED TOXICOLOGY 40720. Toxicity Testing 409Ernest Hodgson and Helen Cunny20.1 Introduction 40920.2 Experimental Administration of Toxicants 41220.3 Chemical and Physical Properties 41420.4 Exposure and Environmental Fate 41420.5 In Vivo Tests 41520.6 In Vitro and Other Short-Term Tests 44220.7 Ecological Effects 45120.8 Risk Analysis 45320.9 The Future of Toxicity Testing 453Bibliography and Suggested Reading 454Sample Questions 45521. Forensic and Clinical Toxicology 457Sharon A. Meyer and Bonita L. Blake21.1 Introduction 45721.2 Forensic Toxicology 45721.3 Clinical Toxicology 46221.4 Analytical Methods in Forensic and Clinical Toxicology 469Bibliography and Suggested Reading 472Sample Questions 47322. Prevention of Toxicity 475Ernest Hodgson22.1 Introduction 47522.2 Legislation and Regulation 47522.3 Prevention in Different Environments 48222.4 Education 485Bibliography and Suggested Reading 486Sample Questions 48723. Human Health Risk Assessment 489Ronald E. Baynes23.1 Introduction 48923.2 Risk Assessment Methods 49023.3 Noncancer Risk Assessment 49323.4 Cancer Risk Assessment 50023.5 PBPK Modeling 503Bibliography and Suggested Reading 504Sample Questions 505PART VII ENVIRONMENTAL TOXICOLOGY 50724. Toxicant Analysis: Analytical Methods and Quality Assurance 509Chris Hofelt24.1 Introduction 50924.2 Environmental Sample Collection Methods 51024.3 Analytical Techniques 51424.4 Quantifi cation, QA, and QC 52524.5 Summary 528Bibliography and Suggested Reading 528Sample Questions 52925. Basics of Environmental Toxicology 531Gerald A. Leblanc and David B. Buchwalter25.1 Introduction 53125.2 Environmental Persistence 53225.3 Bioaccumulation 53525.4 Toxicity 53925.5 Conclusion 546Bibliography and Suggested Reading 547Sample Questions 54726. Transport and Fate of Toxicants in the Environment 549Damian Shea26.1 Introduction 54926.2 Sources of Toxicants to the Environment 55026.3 Transport Processes 55326.4 Equilibrium Partitioning 55726.5 Transformation Processes 56026.6 Environmental Fate Models 567Bibliography and Suggested Reading 569Sample Questions 56927. Environmental Risk Assessment 571Damian Shea27.1 Introduction 57127.2 Formulating the Problem 57327.3 Analyzing Exposure and Effects Information 57827.4 Characterizing Risk 58227.5 Managing Risk 587Bibliography and Suggested Reading 588Sample Questions 589PART VIII NEW APPROACHES IN TOXICOLOGY 59128. Perspectives on Informatics in Toxicology 593Seth W. Kullman, Carolyn J. Mattingly, Joel N. Meyer, and Andrew Whitehead28.1 Introduction 59328.2 Transcriptomics 59428.3 Annotation Resources 59528.4 Genome Sequencing, Resequencing and Genotyping 59728.5 Epigenomic Profi ling 59828.6 Computational Toxicology 59928.7 Informatics Tools in Toxicology 601Bibliography and Suggested Reading 602Sample Question 60529. Future Considerations 607Ernest Hodgson29.1 Introduction 60729.2 Risk Assessment 60929.3 Risk Management 61329.4 Risk Communication 61329.5 In Vivo Toxicity 61429.6 In Vitro Toxicity 61429.7 Molecular and Biochemical Toxicology 61429.8 Development of Selective Toxicants 61529.9 Summary and Conclusions 616Bibliography and Suggested Reading 616Sample Questions 617GLOSSARY 619INDEX 638

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.

"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)

• PREFACE TO THE FOURTH EDITION xxiCONTRIBUTORS xxiiiPART I INTRODUCTION 11. Introduction to Toxicology 3Ernest Hodgson1.1 Definition and Scope 31.2 Relationship to Other Sciences 91.3 A Brief History of Toxicology 101.4 Dose–Response Relationships 111.5 Sources of Toxic Compounds 121.6 Movement of Toxicants in the Environment 12Bibliography and Suggested Reading 13Sample Questions 142. Introduction to Biochemical and Molecular Methods in Toxicology 15Ernest Hodgson, Gerald A. Leblanc, Sharon A. Meyer, and Robert C. Smart2.1 Introduction 152.2 Cell Culture Techniques 152.3 Molecular Techniques 192.4 Immunochemical Techniques 232.5 Proteomics 262.6 Metabolomics 262.7 Bioinformatics 262.8 Summary and Conclusions 27Bibliography and Suggested Reading 27Sample Questions 27PART II CLASSES OF TOXICANTS 293. Exposure Classes, Toxicants in Air, Water, Soil, Domestic, and Occupational Settings 31W. Gregory Cope3.1 Air Pollutants 313.2 Water and Soil Pollutants 383.3 Occupational Toxicants 42Bibliography and Suggested Reading 46Air Pollutants 46Water and Soil Pollutants 47Occupational Toxicants 47Sample Questions 474. Classes of Toxicants: Use Classes 49W. Gregory Cope and Ernest Hodgson4.1 Introduction 494.2 Metals 494.3 Agricultural Chemicals (Pesticides) 554.4 Food Additives and Contaminants 654.5 Toxins 664.6 Solvents 714.7 Therapeutic Drugs 714.8 Drugs of Abuse 724.9 Combustion Products 724.10 Cosmetics 74Bibliography and Suggested Reading 74General 74Metals 74Pesticides 75Toxins 75Solvents 75Therapeutic Drugs 75Sample Questions 75PART III TOXICANT PROCESSING IN VIVO 775. Absorption and Distribution of Toxicants 79Ronald E. Baynes and Ernest Hodgson5.1 Introduction 795.2 Cell Membranes 805.3 Mechanisms of Transport 825.4 Physicochemical Properties Relevant to Diffusion 875.5 Routes of Absorption 905.6 Toxicant Distribution 995.7 Toxicokinetics 108Bibliography and Suggested Reading 112Sample Questions 1136. Metabolism of Toxicants 115Ernest Hodgson and Randy L. Rose6.1 Introduction 1156.2 Phase I Reactions 1166.3 Phase II Reactions 143Bibliography and Suggested Reading 154Sample Questions 1557. Reactive Metabolites 157Ernest Hodgson and Randy L. Rose7.1 Introduction 1577.2 Activation Enzymes 1587.3 Nature and Stability of Reactive Metabolites 1607.4 Fate of Reactive Metabolites 1617.5 Factors Affecting Toxicity of Reactive Metabolites 1627.6 Reactive Oxygen Species 1637.7 Examples of Activating Reactions 1647.8 Summary and Conclusions 170Bibliography and Suggested Reading 171Sample Questions 1718. Chemical and Physiological Effects on Xenobiotic Metabolism 173Andrew D. Wallace and Ernest Hodgson8.1 Introduction 1738.2 Nutritional Effects 1738.3 Physiological Effects 1768.4 Comparative and Genetic Effects 1828.5 Chemical Effects 1918.6 Environmental Effects 2078.7 Summary and Conclusions 209Bibliography and Suggested Reading 210Sample Questions 2119. Elimination of Toxicants 213Gerald A. Leblanc9.1 Introduction 2139.2 Transport 2159.3 Renal Elimination 2169.4 Hepatic Elimination 2179.5 Respiratory Elimination 2209.6 Conclusion 221Bibliography and Suggested Reading 221Sample Questions 222PART IV TOXIC ACTION 22310. Acute Toxicity 225Gerald A. Leblanc10.1 Introduction 22510.2 Acute Exposure and Effect 22510.3 Dose–Response Relationships 22710.4 Nonconventional Dose–Response Relationships 22910.5 Alternative Methods 23010.6 Mechanisms of Acute Toxicity 231Bibliography and Suggested Reading 236Sample Questions 23611. Chemical Carcinogenesis and Mutagenesis 237Robert C. Smart11.1 DNA Damage and Mutagenesis 23711.2 General Aspects of Cancer 23911.3 Human Cancer 24211.4 Classes of Agents That Are Associated with Carcinogenesis 25111.5 General Aspects of Chemical Carcinogenesis 25411.6 Oncogenes 25911.7 Tumor Suppressor Genes 262Bibliography and Suggested Reading 264Sample Questions 26412. Teratogenesis 265Jill A. Barnes and Ida M. Washington12.1 Introduction 26512.2 Overview of Embryonic Development 26612.3 Principles of Teratogenesis 26812.4 Mechanisms of Teratogenesis 26812.5 Future Considerations 272Bibliography and Suggested Reading 272Sample Questions 272PART V ORGAN TOXICITY 27513. Hepatotoxicity 277Andrew D. Wallace and Sharon A. Meyer13.1 Introduction 27713.2 Susceptibility of the Liver 27913.3 Types of Liver Injury 27913.4 Mechanisms of Hepatotoxicity 28313.5 Examples of Hepatotoxicants 28513.6 Metabolic Activation of Hepatotoxicants 288Bibliography and Suggested Reading 289Sample Questions 28914. Nephrotoxicity 291Joan B. Tarloff and Andrew D. Wallace14.1 Introduction 29114.2 Factors Contributing to Nephrotoxicity 29214.3 Examples of Nephrotoxicants 29314.4 Summary 301Bibliography and Suggested Reading 301Sample Questions 30215. Toxicology of the Nervous System 303Bonita L. Blake15.1 Introduction 30315.2 The Nervous System 30315.3 Toxicant Effects on the Nervous System 31215.4 Neurotoxicity Testing 31715.5 Summary 321Bibliography and Suggested Reading 322Sample Questions 32216. Reproductive System 323Heather Patisaul16.1 Introduction 32316.2 The Hypothalamic-Pituitary-Gonadal Axis 32416.3 Male Reproductive Physiology 32616.4 Disruption of Male Reproduction By Toxicants 33016.5 Female Reproductive Physiology 33216.6 Disruption of Female Reproduction by Toxicants 33516.7 Summary 341Bibliography and Suggested Reading 341Sample Questions 34317. Endocrine Toxicology 345Gerald A. Leblanc17.1 Introduction 34517.2 Endocrine System 34517.3 Endocrine Disruption 35217.4 Incidents of Endocrine Toxicity 35817.5 Conclusion 361Bibliography and Suggested Reading 362Sample Questions 36218. Respiratory Toxicology 363James C. Bonner18.1 Introduction 36318.2 Anatomy and Function of the Respiratory Tract 36318.3 Toxicant-Induced Lung Injury, Remodeling, and Repair 37318.4 Occupational and Environmental Lung Diseases 380Bibliography and Suggested Reading 385Sample Questions 38519. Immune System 387MaryJane K. Selgrade19.1 Introduction 38719.2 The Immune System 38819.3 Immune Suppression 39119.4 Classification of Immune-Mediated Injury (Hypersensitivity) 39619.5 Effects of Chemicals on Allergic Disease 39819.6 Other Issues: Autoimmunity and the DevelopingImmune System 403Bibliography and Suggested Reading 404Sample Questions 404PART VI APPLIED TOXICOLOGY 40720. Toxicity Testing 409Ernest Hodgson and Helen Cunny20.1 Introduction 40920.2 Experimental Administration of Toxicants 41220.3 Chemical and Physical Properties 41420.4 Exposure and Environmental Fate 41420.5 In Vivo Tests 41520.6 In Vitro and Other Short-Term Tests 44220.7 Ecological Effects 45120.8 Risk Analysis 45320.9 The Future of Toxicity Testing 453Bibliography and Suggested Reading 454Sample Questions 45521. Forensic and Clinical Toxicology 457Sharon A. Meyer and Bonita L. Blake21.1 Introduction 45721.2 Forensic Toxicology 45721.3 Clinical Toxicology 46221.4 Analytical Methods in Forensic and Clinical Toxicology 469Bibliography and Suggested Reading 472Sample Questions 47322. Prevention of Toxicity 475Ernest Hodgson22.1 Introduction 47522.2 Legislation and Regulation 47522.3 Prevention in Different Environments 48222.4 Education 485Bibliography and Suggested Reading 486Sample Questions 48723. Human Health Risk Assessment 489Ronald E. Baynes23.1 Introduction 48923.2 Risk Assessment Methods 49023.3 Noncancer Risk Assessment 49323.4 Cancer Risk Assessment 50023.5 PBPK Modeling 503Bibliography and Suggested Reading 504Sample Questions 505PART VII ENVIRONMENTAL TOXICOLOGY 50724. Toxicant Analysis: Analytical Methods and Quality Assurance 509Chris Hofelt24.1 Introduction 50924.2 Environmental Sample Collection Methods 51024.3 Analytical Techniques 51424.4 Quantifi cation, QA, and QC 52524.5 Summary 528Bibliography and Suggested Reading 528Sample Questions 52925. Basics of Environmental Toxicology 531Gerald A. Leblanc and David B. Buchwalter25.1 Introduction 53125.2 Environmental Persistence 53225.3 Bioaccumulation 53525.4 Toxicity 53925.5 Conclusion 546Bibliography and Suggested Reading 547Sample Questions 54726. Transport and Fate of Toxicants in the Environment 549Damian Shea26.1 Introduction 54926.2 Sources of Toxicants to the Environment 55026.3 Transport Processes 55326.4 Equilibrium Partitioning 55726.5 Transformation Processes 56026.6 Environmental Fate Models 567Bibliography and Suggested Reading 569Sample Questions 56927. Environmental Risk Assessment 571Damian Shea27.1 Introduction 57127.2 Formulating the Problem 57327.3 Analyzing Exposure and Effects Information 57827.4 Characterizing Risk 58227.5 Managing Risk 587Bibliography and Suggested Reading 588Sample Questions 589PART VIII NEW APPROACHES IN TOXICOLOGY 59128. Perspectives on Informatics in Toxicology 593Seth W. Kullman, Carolyn J. Mattingly, Joel N. Meyer, and Andrew Whitehead28.1 Introduction 59328.2 Transcriptomics 59428.3 Annotation Resources 59528.4 Genome Sequencing, Resequencing and Genotyping 59728.5 Epigenomic Profi ling 59828.6 Computational Toxicology 59928.7 Informatics Tools in Toxicology 601Bibliography and Suggested Reading 602Sample Question 60529. Future Considerations 607Ernest Hodgson29.1 Introduction 60729.2 Risk Assessment 60929.3 Risk Management 61329.4 Risk Communication 61329.5 In Vivo Toxicity 61429.6 In Vitro Toxicity 61429.7 Molecular and Biochemical Toxicology 61429.8 Development of Selective Toxicants 61529.9 Summary and Conclusions 616Bibliography and Suggested Reading 616Sample Questions 617GLOSSARY 619INDEX 638

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.

"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)

• PREFACE TO THE FOURTH EDITION xxiCONTRIBUTORS xxiiiPART I INTRODUCTION 11. Introduction to Toxicology 3Ernest Hodgson1.1 Definition and Scope 31.2 Relationship to Other Sciences 91.3 A Brief History of Toxicology 101.4 Dose–Response Relationships 111.5 Sources of Toxic Compounds 121.6 Movement of Toxicants in the Environment 12Bibliography and Suggested Reading 13Sample Questions 142. Introduction to Biochemical and Molecular Methods in Toxicology 15Ernest Hodgson, Gerald A. Leblanc, Sharon A. Meyer, and Robert C. Smart2.1 Introduction 152.2 Cell Culture Techniques 152.3 Molecular Techniques 192.4 Immunochemical Techniques 232.5 Proteomics 262.6 Metabolomics 262.7 Bioinformatics 262.8 Summary and Conclusions 27Bibliography and Suggested Reading 27Sample Questions 27PART II CLASSES OF TOXICANTS 293. Exposure Classes, Toxicants in Air, Water, Soil, Domestic, and Occupational Settings 31W. Gregory Cope3.1 Air Pollutants 313.2 Water and Soil Pollutants 383.3 Occupational Toxicants 42Bibliography and Suggested Reading 46Air Pollutants 46Water and Soil Pollutants 47Occupational Toxicants 47Sample Questions 474. Classes of Toxicants: Use Classes 49W. Gregory Cope and Ernest Hodgson4.1 Introduction 494.2 Metals 494.3 Agricultural Chemicals (Pesticides) 554.4 Food Additives and Contaminants 654.5 Toxins 664.6 Solvents 714.7 Therapeutic Drugs 714.8 Drugs of Abuse 724.9 Combustion Products 724.10 Cosmetics 74Bibliography and Suggested Reading 74General 74Metals 74Pesticides 75Toxins 75Solvents 75Therapeutic Drugs 75Sample Questions 75PART III TOXICANT PROCESSING IN VIVO 775. Absorption and Distribution of Toxicants 79Ronald E. Baynes and Ernest Hodgson5.1 Introduction 795.2 Cell Membranes 805.3 Mechanisms of Transport 825.4 Physicochemical Properties Relevant to Diffusion 875.5 Routes of Absorption 905.6 Toxicant Distribution 995.7 Toxicokinetics 108Bibliography and Suggested Reading 112Sample Questions 1136. Metabolism of Toxicants 115Ernest Hodgson and Randy L. Rose6.1 Introduction 1156.2 Phase I Reactions 1166.3 Phase II Reactions 143Bibliography and Suggested Reading 154Sample Questions 1557. Reactive Metabolites 157Ernest Hodgson and Randy L. Rose7.1 Introduction 1577.2 Activation Enzymes 1587.3 Nature and Stability of Reactive Metabolites 1607.4 Fate of Reactive Metabolites 1617.5 Factors Affecting Toxicity of Reactive Metabolites 1627.6 Reactive Oxygen Species 1637.7 Examples of Activating Reactions 1647.8 Summary and Conclusions 170Bibliography and Suggested Reading 171Sample Questions 1718. Chemical and Physiological Effects on Xenobiotic Metabolism 173Andrew D. Wallace and Ernest Hodgson8.1 Introduction 1738.2 Nutritional Effects 1738.3 Physiological Effects 1768.4 Comparative and Genetic Effects 1828.5 Chemical Effects 1918.6 Environmental Effects 2078.7 Summary and Conclusions 209Bibliography and Suggested Reading 210Sample Questions 2119. Elimination of Toxicants 213Gerald A. Leblanc9.1 Introduction 2139.2 Transport 2159.3 Renal Elimination 2169.4 Hepatic Elimination 2179.5 Respiratory Elimination 2209.6 Conclusion 221Bibliography and Suggested Reading 221Sample Questions 222PART IV TOXIC ACTION 22310. Acute Toxicity 225Gerald A. Leblanc10.1 Introduction 22510.2 Acute Exposure and Effect 22510.3 Dose–Response Relationships 22710.4 Nonconventional Dose–Response Relationships 22910.5 Alternative Methods 23010.6 Mechanisms of Acute Toxicity 231Bibliography and Suggested Reading 236Sample Questions 23611. Chemical Carcinogenesis and Mutagenesis 237Robert C. Smart11.1 DNA Damage and Mutagenesis 23711.2 General Aspects of Cancer 23911.3 Human Cancer 24211.4 Classes of Agents That Are Associated with Carcinogenesis 25111.5 General Aspects of Chemical Carcinogenesis 25411.6 Oncogenes 25911.7 Tumor Suppressor Genes 262Bibliography and Suggested Reading 264Sample Questions 26412. Teratogenesis 265Jill A. Barnes and Ida M. Washington12.1 Introduction 26512.2 Overview of Embryonic Development 26612.3 Principles of Teratogenesis 26812.4 Mechanisms of Teratogenesis 26812.5 Future Considerations 272Bibliography and Suggested Reading 272Sample Questions 272PART V ORGAN TOXICITY 27513. Hepatotoxicity 277Andrew D. Wallace and Sharon A. Meyer13.1 Introduction 27713.2 Susceptibility of the Liver 27913.3 Types of Liver Injury 27913.4 Mechanisms of Hepatotoxicity 28313.5 Examples of Hepatotoxicants 28513.6 Metabolic Activation of Hepatotoxicants 288Bibliography and Suggested Reading 289Sample Questions 28914. Nephrotoxicity 291Joan B. Tarloff and Andrew D. Wallace14.1 Introduction 29114.2 Factors Contributing to Nephrotoxicity 29214.3 Examples of Nephrotoxicants 29314.4 Summary 301Bibliography and Suggested Reading 301Sample Questions 30215. Toxicology of the Nervous System 303Bonita L. Blake15.1 Introduction 30315.2 The Nervous System 30315.3 Toxicant Effects on the Nervous System 31215.4 Neurotoxicity Testing 31715.5 Summary 321Bibliography and Suggested Reading 322Sample Questions 32216. Reproductive System 323Heather Patisaul16.1 Introduction 32316.2 The Hypothalamic-Pituitary-Gonadal Axis 32416.3 Male Reproductive Physiology 32616.4 Disruption of Male Reproduction By Toxicants 33016.5 Female Reproductive Physiology 33216.6 Disruption of Female Reproduction by Toxicants 33516.7 Summary 341Bibliography and Suggested Reading 341Sample Questions 34317. Endocrine Toxicology 345Gerald A. Leblanc17.1 Introduction 34517.2 Endocrine System 34517.3 Endocrine Disruption 35217.4 Incidents of Endocrine Toxicity 35817.5 Conclusion 361Bibliography and Suggested Reading 362Sample Questions 36218. Respiratory Toxicology 363James C. Bonner18.1 Introduction 36318.2 Anatomy and Function of the Respiratory Tract 36318.3 Toxicant-Induced Lung Injury, Remodeling, and Repair 37318.4 Occupational and Environmental Lung Diseases 380Bibliography and Suggested Reading 385Sample Questions 38519. Immune System 387MaryJane K. Selgrade19.1 Introduction 38719.2 The Immune System 38819.3 Immune Suppression 39119.4 Classification of Immune-Mediated Injury (Hypersensitivity) 39619.5 Effects of Chemicals on Allergic Disease 39819.6 Other Issues: Autoimmunity and the DevelopingImmune System 403Bibliography and Suggested Reading 404Sample Questions 404PART VI APPLIED TOXICOLOGY 40720. Toxicity Testing 409Ernest Hodgson and Helen Cunny20.1 Introduction 40920.2 Experimental Administration of Toxicants 41220.3 Chemical and Physical Properties 41420.4 Exposure and Environmental Fate 41420.5 In Vivo Tests 41520.6 In Vitro and Other Short-Term Tests 44220.7 Ecological Effects 45120.8 Risk Analysis 45320.9 The Future of Toxicity Testing 453Bibliography and Suggested Reading 454Sample Questions 45521. Forensic and Clinical Toxicology 457Sharon A. Meyer and Bonita L. Blake21.1 Introduction 45721.2 Forensic Toxicology 45721.3 Clinical Toxicology 46221.4 Analytical Methods in Forensic and Clinical Toxicology 469Bibliography and Suggested Reading 472Sample Questions 47322. Prevention of Toxicity 475Ernest Hodgson22.1 Introduction 47522.2 Legislation and Regulation 47522.3 Prevention in Different Environments 48222.4 Education 485Bibliography and Suggested Reading 486Sample Questions 48723. Human Health Risk Assessment 489Ronald E. Baynes23.1 Introduction 48923.2 Risk Assessment Methods 49023.3 Noncancer Risk Assessment 49323.4 Cancer Risk Assessment 50023.5 PBPK Modeling 503Bibliography and Suggested Reading 504Sample Questions 505PART VII ENVIRONMENTAL TOXICOLOGY 50724. Toxicant Analysis: Analytical Methods and Quality Assurance 509Chris Hofelt24.1 Introduction 50924.2 Environmental Sample Collection Methods 51024.3 Analytical Techniques 51424.4 Quantifi cation, QA, and QC 52524.5 Summary 528Bibliography and Suggested Reading 528Sample Questions 52925. Basics of Environmental Toxicology 531Gerald A. Leblanc and David B. Buchwalter25.1 Introduction 53125.2 Environmental Persistence 53225.3 Bioaccumulation 53525.4 Toxicity 53925.5 Conclusion 546Bibliography and Suggested Reading 547Sample Questions 54726. Transport and Fate of Toxicants in the Environment 549Damian Shea26.1 Introduction 54926.2 Sources of Toxicants to the Environment 55026.3 Transport Processes 55326.4 Equilibrium Partitioning 55726.5 Transformation Processes 56026.6 Environmental Fate Models 567Bibliography and Suggested Reading 569Sample Questions 56927. Environmental Risk Assessment 571Damian Shea27.1 Introduction 57127.2 Formulating the Problem 57327.3 Analyzing Exposure and Effects Information 57827.4 Characterizing Risk 58227.5 Managing Risk 587Bibliography and Suggested Reading 588Sample Questions 589PART VIII NEW APPROACHES IN TOXICOLOGY 59128. Perspectives on Informatics in Toxicology 593Seth W. Kullman, Carolyn J. Mattingly, Joel N. Meyer, and Andrew Whitehead28.1 Introduction 59328.2 Transcriptomics 59428.3 Annotation Resources 59528.4 Genome Sequencing, Resequencing and Genotyping 59728.5 Epigenomic Profi ling 59828.6 Computational Toxicology 59928.7 Informatics Tools in Toxicology 601Bibliography and Suggested Reading 602Sample Question 60529. Future Considerations 607Ernest Hodgson29.1 Introduction 60729.2 Risk Assessment 60929.3 Risk Management 61329.4 Risk Communication 61329.5 In Vivo Toxicity 61429.6 In Vitro Toxicity 61429.7 Molecular and Biochemical Toxicology 61429.8 Development of Selective Toxicants 61529.9 Summary and Conclusions 616Bibliography and Suggested Reading 616Sample Questions 617GLOSSARY 619INDEX 638