Principles of Toxicology Second Edition2025|PDF|Epub|mobi|kindle电子书版本百度云盘下载

Principles of Toxicology Second EditionPDF格式电子书版下载

注意：本站所有压缩包均有解压码： 点击下载压缩包解压工具

1 Measuring Toxicity and Assessing Risk1

Introduction1

Chemistry of Toxicants1

Toxicity Testing Methods2

Factors to Be Considered in Planning Toxicity Testing2

Routes of Exposure3

Determining the Responses to Varying Doses of a Substance3

Timing of Exposure4

The LD50 Experiment5

Testing5

Analysis6

Alternative Tests7

Categories of Toxicity9

Mixtures9

Toxicity，Hazard，and Risk10

Toxicity and Hazard10

The Role of Laboratory Testing in Estimation of Hazard10

Epidemiological Data11

Risk Assessment and Risk Management12

References13

2 Toxicokinetics15

Introduction15

Pharmacokinetics and Toxicokinetics15

Absorption16

The Oral Route of Absorption17

Respiratory Route of Absorption18

Dermal Route of Absorption18

Distribution18

Elimination19

Toxicokinetic Models20

Mathematical Models of Elimination20

Absorption and Bioavailability23

Contrasting Kinetics of Lipophilic Substances24

References26

3 Biotransformation27

Introduction27

Primary Biotransformation（Phase Ⅰ Reactions）：Hydrolysis28

Serine Hydrolases29

Primary Biotransformation（Phase Ⅰ Reactions）：Oxidation33

The Role of Cytochrome P45033

Other Enzymes Carrying Out Oxidation40

Primary Biotransformation（Phase Ⅰ Reactions）：Reduction41

Secondary Metabolism（Phase Ⅱ Reactions）41

Glucuronidation42

Glutathione Conjugation44

Acetylation and Other Phase Ⅱ Reactions46

Factors That Influence Metabolism47

References47

4 Cellular Sites of Action49

Introduction49

Interaction of Toxicants with Proteins49

Effects of Toxicants on Enzymes51

Effects of Toxicants on Receptors and Ion Channels57

Effects of Toxicants on Voltage-Activated Ion Channels62

Effects of Toxicants on Transport Proteins63

Effects of Toxicants on Lipids64

Effects of Toxicants on Nucleic Acids66

Mechanisms of Cell Death67

Apoptosis67

Necrosis68

Stress，Repair，and Recovery69

Case Study：Cyclooxygenase Inhibitors70

References72

5 Genomics and New Genetics in Toxicology75

Introduction75

The Human Genome Project75

Model Organisms and Comparative Genomics76

Toxicogenomics79

Monitoring Transcription：Gene Expression and Microarrays79

Other Roles for RNA83

SNPs84

Metabolomics86

Personalized Susceptibility and Tailored Therapeutics87

Race，Ethics，and Genomics90

Systems Toxicology92

Case Study：Using GenBank and Online Tools in Genomics92

References95

6 Carcinogenesis97

Cancer97

The Epidemiology of Cancer97

Environmental Factors in Cancer98

Genetic Factors in Cancer99

Carcinogenesis99

The Mutational Theory of Carcinogenesis99

Competing Theories100

Chemical Carcinogens100

Genetic Carcinogens101

Consequences of Mutagenesis103

Epigenetic Carcinogens and Promotion103

Oncogenes and Tumor Suppressor Genes105

The Discovery of Oncogenes105

An Example of an Oncogene：The Philadelphia Chromosome106

The Role of Protooncogenes in Cell Function106

Examples of Protooncogenes107

Tumor Suppressor Genes108

Protection against the Development of Cancer110

Testing Compounds for Carcinogenicity110

Critiques of Strategies in Cancer Research112

Carcinogenesis：A Complex Process112

Case Study：Predicting Carcinogenesis Based upon Chemistry（QSAR）113

References115

7 Reproductive Toxicology and Teratology117

Introduction117

Basic Processes in Reproduction and Development：Cell Division117

The Cell Cycle and Mitosis117

Meiosis120

Cloning122

The Male Reproductive System123

The Female Reproductive System124

The Effects of Toxicants on the Male and Female Reproductive Systems125

Protective Mechanisms：The Blood-Testis Barrier125

Interference with Cell Division126

Cytotoxicity and Infertility126

Interference with Hormonal Controls127

The Process of Development129

Embryogenesis and Developmental Genetics131

Effects of Toxicants on Development：Teratogens and Teratogenesis133

Effects of Dose or Exposure Level on Teratogenicity133

Effects of Timing of Exposure on Teratogenicity134

Examples of Teratogens134

Mechanisms of Teratogenicity136

Testing for Reproductive and Developmental Toxicity137

Human Assessment137

Testing of Laboratory Animals：General Principles137

In Vitro Testing138

Established Procedures for Testing138

Case Study：Thalidomide139

References141

8 Respiratory Toxicology143

Function of the Respiratory System143

Anatomy and Physiology of the Respiratory System143

Respiratory Anatomy143

Pulmonary Ventilation146

Gas Exchange147

Control of Respiration149

Effects of Toxicants on the Respiratory System：General Principles150

Defense Mechanisms of the Respiratory System150

Exposure to Respiratory Toxicants151

Measuring Exposure Levels151

Deposition of Gases152

Deposition of Particulates152

Immediate Responses to Respiratory Toxicants153

Free Radical-Induced Damage153

The Irritant Response154

Involvement of the Immune System154

Immediate Responses：Upper Airway Effects154

Immediate Responses：Lower Airway Effects155

Delayed and Cumulative Responses to Respiratory Toxicants155

Asthma and Immune-Related Chronic Conditions156

Chronic Obstructive Pulmonary Disease：Bronchitis and Emphysema156

Fibrosis and Pneumoconioses157

Lung Cancer158

Inhalation Studies160

References160

9 Cardiovascular Toxicology163

Function of the Cardiovascular System163

Anatomy and Physiology of the Heart163

Effects of Toxicants on the Heart166

Arrhythmias166

Cardiomyopathies and Other Effects on Cardiac Muscle168

Myocardial Infarctions169

The Vascular System170

Effects of Toxicants on the Vascular System172

Atherosclerosis172

Vascular Spasms and Blood Pressure173

The Blood174

Effects of Toxicants on the Blood175

Anemias，Hemolysis，and Related Disorders175

Effects of Toxicants on Hemoglobin177

References178

10 Neurotoxicology181

Function of the Nervous System181

Anatomy and Physiology of the Nervous System181

Effects of Toxicants on the Nervous System：General Principles183

The Blood-Brain Barrier184

Effects of Toxicants on the Nervous System：General Categories185

Effects of Toxicants on Electrical Conduction186

Effects of Toxicants on Synaptic Function190

Acetylcholine192

Biogenic Amines196

Amino Acid Neurotransmitters199

Neuroactive Peptides200

Axonopathies201

Axon Transport Systems201

Proximal Axonopathies203

Distal Axonopathies203

Myelinopathies205

Effects of Toxicants Directly on Neurons207

Excitotoxicity208

Other Cytotoxic Compounds210

Other Neurotoxicants211

Effects on Special Sensory Organs212

Developmental Effects212

Methods in Neurotoxicology213

Case Study：Botulinum Toxin215

References217

11 Hepatic Toxicology219

Anatomy and Physiology of the Liver219

Liver Structure219

Function of the Liver221

Types of Toxicant-Induced Liver Injury223

Fatty Liver223

Liver Cell Death：Necrosis and Apoptosis225

Cirrhosis228

Carcinogenesis228

Miscellaneous Effects228

Response to Liver Injury229

Evaluating Liver Injury and Treating Disease229

Case Study：Reye’s Syndrome230

References231

12 Renal Toxicology233

Function of the Kidneys233

Anatomy and Physiology of the Kidneys233

Effects of Toxicants on the Kidney：General Principles235

Damage to the Glomerulus235

Damage to the Proximal Tubule237

The Remainder of the Tubule242

Measurement of Kidney Function In Vivo242

Measurement of Kidney Function In Vitro244

References245

13 Immunotoxicology247

Function of the Immune System247

Nonspecific Defense Mechanisms247

The Skin and Mucus Membranes247

Phagocytosis248

The Complement System and Interferons248

Fever248

The Inflammatory Response249

Specific Defense Mechanisms250

Cellular Immunity251

Humoral Immunity252

Development of Immunity253

Effects of Toxicants on the Immune System254

Toxicant-Induced Allergies254

Toxicant-Induced Autoimmunity255

Toxicant-Induced Immunosuppression256

AIDS and Antiviral Drugs258

Methods for Studying Immunotoxicity259

References260

14 Ecological Toxicology261

Introduction261

Effects of Toxicants at the Population Level261

Population Genetics261

Natural Selection262

Natural Selection，Toxicants，and Resistance263

Recombinant Organisms264

Population Growth and Dynamics265

Effects of Toxicants at the Community Level266

Effects of Toxicants at the Ecosystem Level268

Energy Flow in Ecosystems268

Material Cycling in Ecosystems269

Examples of Ecosystems and Vulnerability to Impact by Toxicants271

Marine Ecosystems271

Freshwater Ecosystems273

Terrestrial Ecosystems275

Ecotoxicological Testing Methods276

Single Species Testing276

Microcosms277

Field Studies278

Mathematical Modeling278

Molecular and Cellular Ecotoxicology：A New Direction279

References279

15 Applications：Pharmacology and Toxicology281

Basic Principles of Pharmacology281

Pharmacokinetics and Drug Delivery281

The Magic Bullet：Mechanisms of Action and Side Effects283

Drug Development and the Role of Toxicology284

Preclinical Studies285

Clinical Studies286

Toxicogenomics and Drug Safety287

The Return of Natural Products：Regulatory Issues288

References288

16 Applications：Forensic Toxicology291

Analytical Toxicology291

Thin-Layer Chromatography292

Gas Chromatography-Mass Spectrometry293

High-Performance Liquid Chromatography294

Immunoassays296

Forensic Toxicology and Alcohol Use297

Forensic Toxicology and Illegal Drug Use298

The Controlled Substances Act298

Drug Identification299

Major Categories of Illegal Drugs：Neuroactive Drugs299

Anabolic Steroids300

Criminal Poisonings301

References303

17 Applications：Environmental Toxicology and Pollution305

Air Pollution305

Types and Sources of Air Pollutants305

General Effects of Air Pollutants305

Carbon Oxides306

Sulfur Oxides and Nitrogen Oxides308

Hydrocarbons and the Formation of Secondary Pollutants（Including Ozone）310

Chlorofluorocarbons310

Particulates311

Airborne Toxicants312

Indoor Air Pollution312

Control of Air Pollution313

Water Pollution313

Water in the Ecosystem314

Organic Wastes as Water Pollutants315

Petroleum Products as Water Pollutants316

Pesticides318

Other Organic Compounds322

Phosphorus and Nitrogen323

Metals324

Other Pollutants326

Regulation and Control of Water Pollution326

Toxic Wastes327

Sources of Toxic Wastes327

Categories of Waste328

Love Canal and Hazardous Waste Legislation328

Waste Management：Reduce，Recycle，Treat，Store330

References332

Appendix List of Selected Toxicants335

References351

Index353