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PRINCIPLES of BIOCHEMICAL TOXICOLOGY
JOHN TIMBRELL
2005
2000
4MB
PDF






Preface x
CHAPTER 1 INTRODUCTION 1
1.1 Background 1
1.2 Scope 1
1.3 Biochemical aspects of toxicology 2
1.4 Summary 4
1.5 Review questions 5
1.6 Bibliography 5
CHAPTER 2 DOSE-RESPONSE RELATIONSHIPS 7
2.1 Introduction 7
2.2 Criteria of toxicity 7
2.3 Dose-response 11
2.4 Measurement of dose-response relationships 16
2.5 Hazard and risk assessment 20
2.6 Chronic toxicity 21
2.7 Summary 22
2.8 Review questions 22
2.9 Bibliography 22
CHAPTER 3 FACTORS AFFECTING TOXIC RESPONSES: DISPOSITION 25
3.1 Absorption 25
3.2 Sites of absorption 33
3.3 Distribution 42
3.4 Excretion 55
3.5 Summary 60
3.6 Review questions 61
3.7 Bibliography 62
CHAPTER 4 FACTORS AFFECTING TOXIC RESPONSES: METABOLISM 65
4.1 Introduction 65
4.2 Types of metabolic change 67
Contents
4.3 Phase 1 reactions 68
4.4 Phase 2 reactions 95
4.5 Control of metabolism 106
4.6 Toxication versus detoxication 107
4.7 Summary 109
4.8 Review questions 110
4.9 Bibliography 110
CHAPTER 5 FACTORS AFFECTING METABOLISM AND DISPOSITION 113
5.1 Introduction 113
5.2 Chemical factors 114
5.3 Biological factors 117
5.4 Summary 169
5.5 Review questions 171
5.6 Bibliography 172
CHAPTER 6 TOXIC RESPONSES TO FOREIGN COMPOUNDS 175
6.1 Introduction 175
6.2 Direct toxic action: tissue lesions 176
6.3 Pharmacological, physiological and biochemical effects 211
6.4 Teratogenesis 215
6.5 Immunotoxicity 227
6.6 Genetic toxicity 233
6.7 Chemical carcinogenesis 243
6.8 Summary 250
6.9 Review questions 252
6.10 Bibliography 253
CHAPTER 7 BIOCHEMICAL MECHANISMS OF TOXICITY:
SPECIFIC EXAMPLES 259
7.1 Chemical carcinogenesis 259
7.2 Tissue lesions: liver necrosis 269
7.3 Tissue lesions: kidney damage 285
7.4 Tissue lesions: lung damage 290
7.5 Neurotoxicity 294
7.6 Exaggerated and unwanted pharmacological effects 297
7.7 Physiological effects 304
7.8 Biochemical effects: lethal synthesis and incorporation 307
7.9 Biochemical effects: interaction with specific protein receptors 311
7.10 Teratogenesis 316
7.11 Immunotoxicity 321
7.12 Multi-organ toxicity 330
7.13 Multi-organ toxicity: metals 334
7.14 Summary 341
7.15 Review questions 348
7.16 Bibliography 349
Answers to review questions 354
Glossary 365
Index 378
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