About the Author |
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xix | |
Foreword |
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xxi | |
Preface |
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xxiii | |
Unit I |
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Chapter 1 Introduction and historical background |
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3 | (6) |
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3 | (1) |
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1.2 Historical Background |
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3 | (3) |
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3 | (1) |
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4 | (1) |
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1.2.3 Age of Enlightenment |
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5 | (1) |
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6 | (3) |
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6 | (3) |
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Chapter 2 Definitions and scope of toxicology |
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9 | (10) |
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9 | (1) |
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2.2 Sub-disciplines of Toxicology |
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10 | (1) |
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2.3 Toxicant and Types of Toxicants |
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11 | (1) |
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2.4 Toxicity and Toxic Effects |
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12 | (1) |
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2.4.1 Toxicity in Relation to Frequency and Duration of Exposure |
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12 | (1) |
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2.4.2 Toxicity in Relation to Time of Development and Duration of Induced Effects |
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13 | (1) |
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2.5 Dose and Related Terms |
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13 | (1) |
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14 | (1) |
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15 | (1) |
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2.7.1 Accidental Poisoning |
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16 | (1) |
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2.7.2 Malicious Poisoning |
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16 | (1) |
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2.7.3 Occupational Exposure |
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16 | (1) |
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2.8 Duration and Frequency of Exposure |
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16 | (3) |
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Chapter 3 Classification of poisons/toxicants |
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19 | (4) |
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19 | (1) |
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3.2 Classification of Poisons |
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19 | (2) |
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21 | (2) |
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Chapter 4 Factors affecting toxicity |
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23 | (8) |
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23 | (1) |
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4.2 Factors Affecting Toxicity |
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23 | (8) |
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24 | (2) |
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4.2.2 Factors Related to the Toxicant or Associated With Xenobiotics |
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26 | (2) |
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4.2.3 Environmental Conditions |
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28 | (3) |
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Chapter 5 Natural laws concerning toxicology |
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31 | (14) |
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31 | (1) |
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32 | (1) |
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32 | (3) |
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35 | (1) |
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5.5 Dose—Response Relationship |
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36 | (3) |
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5.5.1 Graded or Gradual Dose—Response Relationship |
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36 | (2) |
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5.5.2 Quantal or All-or-None Dose—Response Relationship |
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38 | (1) |
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5.6 Statistical Concept of Toxicity |
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39 | (1) |
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5.7 Variables of Dose—Response Curve |
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40 | (1) |
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5.8 Frequently Used Terms for Safety Evaluation of Drugs |
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41 | (1) |
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5.9 Interaction With Receptors |
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42 | (1) |
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5.10 Types of Xenobiotics |
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42 | (1) |
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5.11 Xenobiotic/Drug Interaction |
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42 | (1) |
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5.12 Nature and Extent of Toxicity Testing |
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43 | (2) |
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Chapter 6 Hazard and risk assessment |
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45 | (10) |
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45 | (1) |
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6.2 Risk Assessment Approach |
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46 | (5) |
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6.2.1 Preliminary Evaluation |
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47 | (1) |
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6.2.2 Toxicity Assessment |
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47 | (2) |
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6.2.3 Exposure Assessment |
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49 | (2) |
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51 | (4) |
Unit II |
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Chapter 7 Absorption, distribution, and excretion of toxicants |
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55 | (18) |
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55 | (1) |
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7.2 Translocation of Xenobiotics Across Membranes |
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56 | (4) |
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7.2.1 Membrane Permeability |
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56 | (1) |
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7.2.2 Mechanism of Chemical Transfer |
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57 | (1) |
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7.2.3 Processes of Transport |
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57 | (3) |
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60 | (4) |
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7.3.1 Gastrointestinal Absorption |
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60 | (2) |
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62 | (1) |
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63 | (1) |
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7.3.4 Parenteral Administration |
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63 | (1) |
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64 | (4) |
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7.4.1 Tissue Permeability Barriers |
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65 | (1) |
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7.4.2 Transfer Across Other Membranes |
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66 | (1) |
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7.4.3 Factors Affecting Distribution and Tissue Retention |
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66 | (2) |
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7.4.4 Binding to Biological Macromolecules and Toxic Effects |
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68 | (1) |
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68 | (1) |
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68 | (5) |
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69 | (1) |
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70 | (1) |
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7.5.3 Gastrointestinal Tract |
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71 | (1) |
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71 | (1) |
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71 | (1) |
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72 | (1) |
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72 | (1) |
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72 | (1) |
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72 | (1) |
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Chapter 8 Biotransformation |
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73 | (14) |
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73 | (1) |
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8.2 Functions of Biotransformation |
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73 | (1) |
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8.3 Xenobiotic Metabolizing Enzymes |
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74 | (1) |
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8.4 Pathways of Biotransformation |
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75 | (7) |
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8.4.1 Phase I Reactions (Nonsynthetic or Nonconjugative Phase) |
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75 | (3) |
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8.4.2 Phase II Reactions or Conjugation/Synthetic Reactions |
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78 | (4) |
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8.5 Complex Nature of Biotransformation |
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82 | (1) |
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8.6 Induction and Inhibition of Metabolizing Enzymes |
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82 | (1) |
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8.6.1 Induction of Enzymes |
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82 | (1) |
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8.6.2 Inhibition of Enzymes |
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83 | (1) |
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8.7 Bioactivation and Tissue Toxicity |
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83 | (4) |
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84 | (1) |
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84 | (1) |
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85 | (1) |
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85 | (2) |
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Chapter 9 Principles and basic concepts of toxicokinetics |
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87 | (24) |
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87 | (1) |
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9.2 Essentials of Toxicokinetics/Pharmacokinetics Principles |
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88 | (1) |
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9.3 Plasma Drug Concentration Versus Time |
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88 | (2) |
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9.4 Orders of Rate Processes |
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90 | (1) |
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9.4.1 Zero-Order Process/Zero-Order Kinetics |
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90 | (1) |
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9.4.2 First-Order Process/First-Order Kinetics |
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90 | (1) |
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9.4.3 Mixed-Order Process/Mixed-Order Kinetics |
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90 | (1) |
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9.5 Toxicokinetics Models |
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91 | (15) |
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9.5.1 Classic Toxicokinetics |
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91 | (12) |
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9.5.2 Noncompartment Models/Noncompartment Analysis |
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103 | (1) |
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9.5.3 Physiological-Based Toxicokinetics |
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104 | (2) |
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9.6 Determination of Dose/Dosage Regimen |
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106 | (1) |
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107 | (4) |
Unit III |
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Chapter 10 Toxicological testing: genesis |
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111 | (12) |
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111 | (1) |
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10.2 Laws and Regulations |
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112 | (5) |
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10.2.1 Regulation in the United States |
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112 | (1) |
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10.2.2 Guidelines for Drugs |
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113 | (2) |
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10.2.3 Toxic Substances Control Act of the United States |
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115 | (1) |
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10.2.4 REACH Regulation of European Countries |
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116 | (1) |
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10.3 International Harmonization |
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117 | (1) |
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10.4 Role of Animal Testing |
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117 | (1) |
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10.5 Standard Information Requirements |
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118 | (1) |
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119 | (2) |
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10.6.1 Avoid Unnecessary Testing |
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119 | (1) |
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10.6.2 Alternate Approaches |
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119 | (1) |
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120 | (1) |
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120 | (1) |
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10.7 Good Laboratory Practices |
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121 | (2) |
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122 | (1) |
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10.7.2 Principles of Good Laboratory Practices |
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122 | (1) |
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Chapter 11 Toxicological testing: in vitro models |
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123 | (8) |
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123 | (1) |
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11.2 Animal Welfare Legislation |
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123 | (1) |
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124 | (2) |
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11.3.1 Permanent Cell Lines |
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124 | (1) |
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125 | (1) |
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11.3.3 Organotypic or Whole Organ Cultures |
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126 | (1) |
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11.4 In Vitro Embryotoxicity Testing |
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126 | (4) |
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11.4.1 Principles of In Vitro Embryotoxicity Testing |
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127 | (1) |
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11.4.2 Use of In Vitro Models/Alternative Test Methods |
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128 | (1) |
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11.4.3 Rat/Mice Embryos as a Model |
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128 | (1) |
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11.4.4 Use of Cultured Embryos |
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129 | (1) |
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11.4.5 Endpoint Determination for In Vitro Testing Systems |
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130 | (1) |
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130 | (1) |
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Chapter 12 Toxicological testing: In vivo systems |
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131 | (20) |
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132 | (1) |
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12.2 Administration of Toxicants |
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132 | (2) |
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12.2.1 Routes of Administration |
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132 | (1) |
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12.2.2 Chemical and Physical Properties |
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133 | (1) |
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12.2.3 Exposure and Environmental Fate |
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134 | (1) |
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134 | (6) |
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12.3.1 Acute and Subchronic Toxicity Tests |
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134 | (1) |
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12.3.2 Acute Oral Toxicity Testing |
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135 | (1) |
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135 | (1) |
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12.3.4 Dermal Irritation and Sensitization |
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136 | (1) |
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12.3.5 Safety Pharmacology Studies |
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137 | (1) |
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137 | (1) |
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12.3.7 Repeated-Dose Dermal Tests |
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138 | (1) |
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12.3.8 28-Day to 90-Day Inhalation Tests |
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138 | (1) |
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139 | (1) |
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12.3.10 Chronic Toxicity and Carcinogenicity |
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139 | (1) |
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12.4 Development and Reproductive Toxicity |
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140 | (7) |
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141 | (1) |
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12.4.2 Single- and Multiple-Generation Tests |
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142 | (2) |
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144 | (2) |
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12.4.4 Perinatal and Postnatal Effects |
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146 | (1) |
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147 | (2) |
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148 | (1) |
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12.5.2 Potentiation and Synergism |
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149 | (1) |
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12.5.3 Toxicokinetics and Metabolism |
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149 | (1) |
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149 | (1) |
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149 | (1) |
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12.6 In Vitro and Other Short-Term Tests |
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149 | (1) |
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150 | (1) |
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150 | (1) |
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151 | (14) |
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151 | (1) |
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13.2 Historical Background |
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152 | (1) |
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152 | (2) |
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154 | (1) |
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13.5 Mutagens Are Carcinogens |
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155 | (1) |
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13.6 Impact on Human Health |
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155 | (1) |
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13.7 DNA Damage and Mechanism |
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156 | (1) |
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13.8 Regulatory Requirements/Guidelines |
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157 | (1) |
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13.9 Assays for Detection of Genetic Alterations |
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157 | (7) |
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13.9.1 Prokaryote Mutagenicity |
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158 | (1) |
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13.9.2 Eukaryote Mutagenicity |
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159 | (2) |
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13.9.3 DNA Damage and Repair |
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161 | (1) |
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13.9.4 Chromosome Aberrations |
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161 | (2) |
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13.9.5 Mammalian Cell Transformation |
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163 | (1) |
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164 | (1) |
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Chapter 14 Preclinical toxicological investigations of pharmaceutical products |
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165 | (8) |
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165 | (1) |
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14.2 Safety Evaluation of Pharmaceutical Products |
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166 | (5) |
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167 | (2) |
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14.2.2 Preclinical Toxicology Testing |
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169 | (1) |
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14.2.3 Preclinical Development Phase |
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169 | (1) |
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14.2.4 Studies of Environmental Safety |
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170 | (1) |
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14.2.5 Postmarketing Surveillance |
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170 | (1) |
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14.2.6 Estimation of the Dose |
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170 | (1) |
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171 | (2) |
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Chapter 15 Preclinical safety evaluation of biotechnology-derived products |
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173 | (4) |
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173 | (1) |
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173 | (1) |
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15.3 Regulatory Considerations |
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174 | (1) |
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174 | (1) |
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15.5 General Toxicological Profile |
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174 | (2) |
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15.5.1 Absorption, Disposition, and Clearance in Relevant Animal Models |
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175 | (1) |
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15.5.2 Specific Toxicity Tests |
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175 | (1) |
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176 | (1) |
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Chapter 16 Preclinical regulatory toxicology for biomaterials and medical devices |
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177 | (8) |
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177 | (1) |
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178 | (1) |
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178 | (1) |
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16.4 Extract Preparations |
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178 | (1) |
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178 | (1) |
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179 | (1) |
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179 | (1) |
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179 | (1) |
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16.6.3 Hemolytic Properties |
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179 | (1) |
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16.6.4 Intracutaneous/Intradermal Reactivity Test |
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179 | (1) |
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180 | (1) |
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180 | (1) |
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16.7.1 Delayed Hypersensitivity/Sensitization Test |
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180 | (1) |
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180 | (1) |
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181 | (1) |
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181 | (1) |
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16.8.1 Subchronic Toxicity |
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181 | (1) |
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181 | (1) |
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181 | (1) |
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16.8.4 Developmental and Reproductive Toxicity |
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182 | (1) |
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182 | (3) |
Unit IV |
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Chapter 17 Toxic effects of pesticides (agrochemicals) |
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185 | (18) |
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185 | (1) |
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17.2 Historical Background |
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186 | (1) |
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17.3 Definition and Classification |
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186 | (1) |
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187 | (11) |
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187 | (2) |
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17.4.2 OP and CM Compounds |
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189 | (3) |
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192 | (3) |
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17.4.4 Botanical Insecticides |
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195 | (1) |
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17.4.5 Pyrethroid Insecticides |
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196 | (1) |
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17.4.6 New Insecticide Classes |
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196 | (2) |
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198 | (1) |
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199 | (1) |
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200 | (1) |
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201 | (2) |
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17.8.1 Aluminum Phosphide |
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202 | (1) |
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17.8.2 Naphthalene (Mothballs) |
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202 | (1) |
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Chapter 18 Toxic effects of metals |
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203 | (12) |
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203 | (1) |
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18.2 Arsenic (Sankhyal, Somalkar) |
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203 | (2) |
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18.3 Mercury (Quick Silver, Liquid Metal, Para, Padarasa) |
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205 | (3) |
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208 | (3) |
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18.5 Copper (Thambe, Blue Vitriol) |
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211 | (1) |
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212 | (3) |
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Chapter 19 Toxic effects of nonmetallics |
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215 | (6) |
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215 | (1) |
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19.2 Toxicity of Nonmetallics |
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215 | (1) |
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216 | (2) |
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218 | (1) |
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218 | (1) |
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219 | (1) |
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19.7 Formaldehyde (Formalin, Methyl Aldehyde, Methylene Oxide) |
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220 | (1) |
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Chapter 20 Neurotoxic agents |
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221 | (24) |
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221 | (1) |
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20.2 Opium (Afim) Derivatives |
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222 | (3) |
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224 | (1) |
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20.3 Pethidine (Meperidine) |
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225 | (1) |
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20.3.1 Pethidine Addiction |
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225 | (1) |
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226 | (3) |
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229 | (1) |
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230 | (1) |
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230 | (1) |
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20.8 Chloral Hydrate (Trichloroacetaldehyde) |
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231 | (1) |
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231 | (3) |
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232 | (2) |
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234 | (1) |
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235 | (1) |
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236 | (1) |
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236 | (1) |
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237 | (3) |
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20.14.1 Cannabis Addiction |
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239 | (1) |
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240 | (3) |
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242 | (1) |
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243 | (2) |
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Chapter 21 Toxic effects of cardiac poisons |
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245 | (8) |
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245 | (1) |
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245 | (2) |
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247 | (2) |
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249 | (4) |
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Chapter 22 Toxic effects of asphyxiants |
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253 | (14) |
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253 | (1) |
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253 | (1) |
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22.2.1 Chemical Asphyxiants |
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254 | (1) |
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22.2.2 Simple Asphyxiants |
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254 | (1) |
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22.2.3 Respiratory/Pulmonary Irritant Asphyxiants |
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254 | (1) |
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22.2.4 Systemic Asphyxiants |
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254 | (1) |
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254 | (2) |
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256 | (1) |
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22.5 Cyanide (Prussic Acid, Cyanogen) |
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257 | (3) |
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260 | (2) |
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262 | (5) |
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22.7.1 Lachrymators (Tear Gases) |
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262 | (1) |
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22.7.2 Lung Irritants (Asphyxiants, Choking Gases) |
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262 | (1) |
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22.7.3 Nasal Irritants and Vomiting Gases (Sternutators) |
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263 | (1) |
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263 | (1) |
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22.7.5 Vesicants (Blister Gases) |
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263 | (1) |
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22.7.6 Paralysants (Nerve and Blood Poisons) |
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264 | (1) |
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22.7.7 Miscellaneous War Gases |
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264 | (3) |
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Chapter 23 Toxic effects of caustics (corrosives) |
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267 | (10) |
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267 | (1) |
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267 | (1) |
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268 | (7) |
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23.3.1 Inorganic Acids/Mineral Acids |
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268 | (3) |
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271 | (4) |
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275 | (2) |
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Chapter 24 Drug toxicity, dependence, and abuse |
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277 | (10) |
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277 | (1) |
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24.2 Aspirin and Other Salicylates |
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278 | (1) |
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278 | (1) |
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24.4 Drug Dependence and Abuse |
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279 | (6) |
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24.4.1 Definitions and Terminology |
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279 | (3) |
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24.4.2 Hallucinogens (Psychedelics) |
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282 | (1) |
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24.4.3 Lysergic Acid Diethylamide |
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282 | (2) |
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284 | (1) |
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24.4.5 Amphetamines (Central Nervous System Stimulant, Hallucinogen) |
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284 | (1) |
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24.4.6 Carbon Tetrachloride |
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285 | (1) |
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24.5 Withdrawal Symptoms (Abstinence Syndrome) |
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285 | (2) |
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Chapter 25 Toxic effects of domestic chemicals |
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287 | (6) |
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25.1 Domestic/Household Poisons Classification |
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287 | (1) |
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287 | (3) |
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25.2.1 Aliphatic Hydrocarbons |
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287 | (3) |
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25.2.2 Aromatic Hydrocarbons |
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290 | (1) |
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25.2.3 Halogenated Hydrocarbons |
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290 | (1) |
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25.3 Other Than Hydrocarbons |
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290 | (3) |
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Chapter 26 Toxic effects of poisonous plants |
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293 | (12) |
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293 | (1) |
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293 | (2) |
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26.3 Ricinus communis (Castor Oil Plant) |
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295 | (1) |
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296 | (1) |
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297 | (1) |
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26.6 Semecarpus anacardium |
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298 | (1) |
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299 | (1) |
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300 | (1) |
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26.9 Colchicum (Colchicum autumnale) |
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301 | (1) |
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302 | (3) |
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Chapter 27 Poisonous foods and food poisoning |
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305 | (6) |
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305 | (1) |
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305 | (1) |
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306 | (1) |
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307 | (1) |
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308 | (3) |
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Chapter 28 Poisons of animal origin |
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311 | (16) |
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311 | (1) |
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312 | (1) |
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312 | (5) |
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313 | (2) |
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28.3.2 Myriapods (Centipedes, Chilopoda) |
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315 | (1) |
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316 | (1) |
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28.3.4 Cantharides (Spanish Fly Blister Beetle, Lytta) |
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317 | (1) |
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317 | (1) |
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317 | (1) |
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318 | (9) |
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318 | (1) |
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319 | (5) |
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28.5.3 Nonvenomous Snakes |
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324 | (1) |
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28.5.4 Other Reptile Bites |
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325 | (1) |
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28.5.5 Alligators and Crocodile |
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|
325 | (1) |
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325 | (2) |
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Chapter 29 Chemical food poisoning |
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327 | (6) |
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327 | (1) |
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327 | (1) |
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29.3 Poisonous Plant Toxins |
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328 | (1) |
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29.4 Poisonous Marine Bites and Stings |
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329 | (4) |
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329 | (1) |
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330 | (3) |
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Chapter 30 Health effects of radioactive materials |
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333 | (10) |
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333 | (2) |
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30.1.1 Historical Background |
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333 | (1) |
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30.1.2 Regulatory Aspects of Radiation |
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334 | (1) |
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30.1.3 Standards for Radiation Exposure |
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334 | (1) |
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30.1.4 Units of Radiation |
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|
335 | (1) |
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335 | (8) |
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30.2.1 Nonionizing Radiation |
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336 | (1) |
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30.2.2 Ionizing Radiation |
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337 | (6) |
Unit V |
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Chapter 31 Basic concepts of forensic toxicology |
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343 | (4) |
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343 | (1) |
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31.2 History and Background |
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343 | (1) |
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344 | (1) |
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344 | (3) |
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31.4.1 Collection of Information |
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344 | (1) |
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31.4.2 Collection of Specimens |
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345 | (1) |
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31.4.3 Toxicological Analysis |
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345 | (1) |
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31.4.4 Documentation and Data Interpretation |
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345 | (2) |
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Chapter 32 Applications in toxicology |
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347 | (8) |
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347 | (1) |
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32.2 Objectives of Analytical Toxicology |
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347 | (1) |
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32.3 Analytical Schemes for Toxicant Detection |
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348 | (1) |
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348 | (2) |
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32.4.1 General Precautions |
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350 | (1) |
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350 | (5) |
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32.5.1 Qualitative Analytical Tests |
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350 | (3) |
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32.5.2 Quantitative Analytical Methods |
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353 | (2) |
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Chapter 33 Clinical toxicology |
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355 | (10) |
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|
355 | (1) |
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33.2 Historical Background |
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|
355 | (1) |
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33.3 Introduction of the Poison Control Center |
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|
356 | (1) |
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33.4 Acute Poisoning Deaths |
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357 | (1) |
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|
357 | (1) |
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33.6 Principles of Diagnosis |
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358 | (3) |
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|
358 | (1) |
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33.6.2 Physical Examination |
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|
358 | (2) |
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33.6.3 Analytical Evidence |
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|
360 | (1) |
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33.7 General Management of Poisoning |
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|
361 | (3) |
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33.7.1 Initial Stabilization |
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|
361 | (1) |
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|
361 | (1) |
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362 | (2) |
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|
364 | (1) |
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33.9 Nursing and Psychiatric Care |
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|
364 | (1) |
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Chapter 34 Treatment of poisoning |
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|
365 | (4) |
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|
365 | (1) |
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34.2 Specific Treatment (Administration of Antidotes) |
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|
365 | (4) |
Further Reading |
|
369 | (12) |
Index |
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381 | |