a textbook of modern toxicology phần 1 docx

[...]... Chemical Effects 9.5 .1 Inhibition 9.5.2 Induction 9.5.3 Biphasic Effects: Inhibition and Induction Environmental Effects General Summary and Conclusions Suggested Reading 10 Elimination of Toxicants 16 3 16 3 16 3 16 4 16 4 16 4 16 5 16 5 16 6 16 6 16 8 16 9 17 1 17 1 17 2 17 2 17 3 18 1 18 1 18 4 18 5 19 0 19 9 19 9 2 01 2 01 203 Gerald A LeBlanc 10 .1 Introduction 203 x CONTENTS 10 .2 Transport 10 .3 Renal Elimination 10 .4 Hepatic... Cysteine Conjugate β-Lyase 7.3.7 Acylation 7.3.8 Phosphate Conjugation Suggested Reading Reactive Metabolites 11 1 11 2 11 2 11 3 12 8 13 0 13 2 13 3 13 5 13 5 13 6 13 7 13 8 13 9 13 9 14 1 14 3 14 5 14 5 14 8 14 8 14 9 Randy L Rose and Patricia E Levi 8 .1 8.2 8.3 8.4 8.5 Introduction Activation Enzymes Nature and Stability of Reactive Metabolites 8.3 .1 Ultra-short-lived Metabolites 8.3.2 Short-lived Metabolites 8.3.3 Longer-lived... 11 .5 .1 Narcosis 11 .5.2 Acetylcholinesterase Inhibition 11 .5.3 Ion Channel Modulators 11 .5.4 Inhibitors of Cellular Respiration Suggested Reading 12 Chemical Carcinogenesis 215 215 217 219 220 220 220 222 223 224 225 Robert C Smart 12 .1 General Aspects of Cancer 12 .2 Human Cancer 12 .2 .1 Causes, Incidence, and Mortality Rates of Human Cancer 12 .2.2 Known Human Carcinogens 12 .2.3 Classification of Human... Elimination 10 .4 .1 Entero-hepatic Circulation 10 .4.2 Active Transporters of the Bile Canaliculus 10 .5 Respiratory Elimination 10 .6 Conclusion Suggested Reading 205 205 207 208 209 210 210 211 IV Toxic Action 213 11 Acute Toxicity 215 Gerald A LeBlanc 11 .1 11. 2 11 .3 11 .4 11 .5 Introduction Acute Exposure and Effect Dose-response Relationships Nonconventional Dose-response Relationships Mechanisms of Acute... of Human Carcinogens 12 .3 Classes of Agents Associated with Carcinogenesis 12 .3 .1 DNA-Damaging Agents 12 .3.2 Epigenetic Agents 12 .4 General Aspects of Chemical Carcinogenesis 12 .5 Initiation-Promotion Model for Chemical Carcinogenesis 12 .6 Metabolic Activation of Chemical Carcinogens and DNA Adduct Formation 12 .7 Oncogenes 12 .7 .1 Mutational Activation of Proto-oncogenes 12 .7.2 Ras Oncogene 12 .8 Tumor... Metabolites Fate of Reactive Metabolites 8.4 .1 Binding to Cellular Macromolecules 8.4.2 Lipid Peroxidation 8.4.3 Trapping and Removal: Role of Glutathione Factors Affecting Toxicity of Reactive Metabolites 8.5 .1 Levels of Activating Enzymes 14 9 15 0 15 1 15 1 15 2 15 2 15 3 15 3 15 3 15 3 15 4 15 4 CONTENTS 8.6 8.7 8.5.2 Levels of Conjugating Enzymes 8.5.3 Levels of Cofactors or Conjugating Chemicals Examples of. .. Hormone Displacement from Binding Proteins 17 .4 Incidents of Endocrine Toxicity 17 .4 .1 Organizational Toxicity 17 .4.2 Activational Toxicity 17 .4.3 Hypothyroidism 17 .5 Conclusion Suggested Reading 18 Respiratory Toxicity xiii 306 306 308 309 310 310 311 311 311 312 313 314 315 317 Ernest Hodgson, Patricia E Levi, and James C Bonner 18 .1 Introduction 18 .1. 1 Anatomy 18 .1. 2 Cell Types 18 .1. 3 Function 18 .2 Susceptibility... physical properties of a chemical and toxicity and, particularly, the use of such relationships as predictors of toxicity 5 Biomathematics and statistics relate to many areas of toxicology They deal with data analysis, the determination of significance, and the formulation of risk estimates and predictive models 6 Epidemiology as it applies to toxicology, is of great importance as it deals with the relationship... Susceptibility of the Respiratory System 18 .2 .1 Nasal 18 .2.2 Lung 18 .3 Types of Toxic Response 18 .3 .1 Irritation 18 .3.2 Cell Necrosis 18 .3.3 Fibrosis 18 .3.4 Emphysema 18 .3.5 Allergic Responses 18 .3.6 Cancer 18 .3.7 Mediators of Toxic Responses 18 .4 Examples of Lung Toxicants Requiring Activation 18 .4 .1 Introduction 18 .4.2 Monocrotaline 18 .4.3 Ipomeanol 18 .4.4 Paraquat 18 .5 Defense Mechanisms Suggested Reading 19 ... Workplace 23.3.3 Pollution of Air, Water, and Land 411 411 412 416 416 417 417 418 419 xvi CONTENTS 23.4 Education Suggested Reading 24 Human Health Risk Assessment 420 4 21 423 Ronald E Baynes 24 .1 Introduction 24.2 Risk Assessment Methods 24.2 .1 Hazard Identification 24.2.2 Exposure Assessment 24.2.3 Dose Response and Risk Characterization 24.3 Noncancer Risk Assessment 24.3 .1 Default Uncertainty and . Smart 12 .1 General Aspects of Cancer 225 12 .2 Human Cancer 228 12 .2 .1 Causes, Incidence, and Mortality Rates of Human Cancer 228 12 .2.2 Known Human Carcinogens 2 31 12.2.3 Classification of Human. LeBlanc 11 .1 Introduction 215 11 .2 Acute Exposure and Effect 215 11 .3 Dose-response Relationships 217 11 .4 Nonconventional Dose-response Relationships 219 11 .5 Mechanisms of Acute Toxicity 220 11 .5 .1. Levels of Cofactors or Conjugating Chemicals 15 4 8.6 Examples of Activating Reactions 15 4 8.6 .1 Parathion 15 5 8.6.2 Vinyl Chloride 15 5 8.6.3 Methanol 15 5 8.6.4 A atoxin B 1 156 8.6.5 Carbon Tetrachloride