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A textbook of modern toxicology

A textbook of modern toxicology

Edition:3rd ed

Author(s) :Ernest Hodgson

Year :2004

ISBN :9780471265085, 9780471646761, 047126508X

Pages :582\582

Language :English

Extension :PDF

Size :6 MB (6634564 bytes)

Summary :

Hodgson (toxicology, North Carolina State University) provides an accessible overview of toxicology, suitable for junior and senior undergraduate courses in environmental, pharmacological, medical, and veterinary toxicology. The text emphasizes the biochemical aspects of toxicology at the cellular and molecular levels, and readers are assumed to have some background in chemistry, biochemistry, and animal physiology. In this third edition, new contributors describe the latest work in their respective areas of specialization and discuss emerging topics such as molecular biological aspects of technology. A glossary and a summary section are included. Table of contents : Team DDU......Page 1 CONTENTS......Page 8 Preface......Page 22 Contributors......Page 24 I Introduction......Page 26 1.1.1 Definition and Scope......Page 28 1.1.3 A Brief History of Toxicology......Page 33 1.3 Sources of Toxic Compounds......Page 35 1.4 Movement of Toxicants in the Environment......Page 36 Suggested Reading......Page 37 2.2 Cell Culture Techniques......Page 38 2.2.3 Indicators of Toxicity in Cultured Cells......Page 39 2.3 Molecular Techniques......Page 41 2.3.2 cDNA and Genomic Libraries......Page 42 2.3.4 Polymerase Chain Reaction (PCR)......Page 43 2.4 Immunochemical Techniques......Page 44 Suggested Reading......Page 47 3.2 General Policies Related to Analytical Laboratories......Page 48 3.2.3 Procedural Manuals......Page 49 3.2.5 Laboratory Information Management System (LIMS)......Page 50 3.3.2 Quantitation Approaches and Techniques......Page 51 3.5 Quality Control (QC) Procedures......Page 52 Suggested Reading......Page 53 II Classes of Toxicants......Page 56 4.1.1 History......Page 58 4.1.2 Types of Air Pollutants......Page 59 4.1.3 Sources of Air Pollutants......Page 60 4.1.4 Examples of Air Pollutants......Page 61 4.1.5 Environmental Effects......Page 63 4.2.1 Sources of Water and Soil Pollutants......Page 65 4.2.2 Examples of Pollutants......Page 66 4.3.1 Regulation of Exposure Levels......Page 69 4.3.2 Routes of Exposure......Page 70 4.3.3 Examples of Industrial Toxicants......Page 71 Suggested Reading......Page 73 5.2.1 History......Page 74 5.2.2 Common Toxic Mechanisms and Sites of Action......Page 75 5.2.3 Lead......Page 76 5.2.5 Cadmium......Page 77 5.2.7 Arsenic......Page 78 5.3.1 Introduction......Page 79 5.3.2 Definitions and Terms......Page 80 5.3.3 Organochlorine Insecticides......Page 82 5.3.4 Organophosphorus Insecticides......Page 83 5.3.6 Botanical Insecticides......Page 85 5.3.8 New Insecticide Classes......Page 86 5.3.9 Herbicides......Page 87 5.3.11 Rodenticides......Page 88 5.4 Food Additives and Contaminants......Page 89 5.5.1 History......Page 90 5.5.3 Mycotoxins......Page 91 5.5.4 Algal Toxins......Page 92 5.5.6 Animal Toxins......Page 93 5.7 Therapeutic Drugs......Page 95 5.10 Cosmetics......Page 96 Suggested Reading......Page 98 III Toxicant Processing In vivo......Page 100 6.1 Introduction......Page 102 6.2 Cell Membranes......Page 103 6.3.1 Passive Diffusion......Page 105 6.3.2 Carrier-Mediated Membrane Transport......Page 108 6.4 Physicochemical Properties Relevant to Diffusion......Page 110 6.4.1 Ionization......Page 111 6.4.2 Partition Coefficients......Page 112 6.5.1 Extent of Absorption......Page 113 6.5.2 Gastrointestinal Absorption......Page 114 6.5.3 Dermal Absorption......Page 116 6.5.4 Respiratory Penetration......Page 119 6.6.1 Physicochemical Properties and Protein Binding......Page 122 6.6.2 Volume of Distribution (Vd )......Page 128 6.7 Toxicokinetics......Page 130 Suggested Reading......Page 134 7.1 Introduction......Page 136 7.2.1 The Endoplasmic Reticulum, Microsomal Preparation, and Monooxygenations......Page 137 7.2.2 The Cytochrome P450-Dependent Monooxygenase System......Page 138 7.2.3 The Flavin-Containing Monooxygenase (FMO)......Page 153 7.2.4 Nonmicrosomal Oxidations......Page 155 7.2.5 Cooxidation by Cyclooxygenases......Page 157 7.2.6 Reduction Reactions......Page 158 7.2.8 Epoxide Hydration......Page 160 7.2.9 DDT Dehydrochlorinase......Page 161 7.3 Phase II Reactions......Page 162 7.3.1 Glucuronide Conjugation......Page 163 7.3.3 Sulfate Conjugation......Page 164 7.3.4 Methyltransferases......Page 166 7.3.5 Glutathione S-Transferases (GSTs) and Mercapturic Acid Formation......Page 168 7.3.7 Acylation......Page 170 Suggested Reading......Page 173 8.1 Introduction......Page 174 8.2 Activation Enzymes......Page 175 8.3.1 Ultra-short-lived Metabolites......Page 176 8.3.3 Longer-lived Metabolites......Page 177 8.4.3 Trapping and Removal: Role of Glutathione......Page 178 8.6 Examples of Activating Reactions......Page 179 8.6.3 Methanol......Page 180 8.6.5 Carbon Tetrachloride......Page 181 8.6.6 Acetylaminofluorene......Page 182 8.6.8 Acetaminophen......Page 183 8.6.9 Cycasin......Page 184 8.7 Future Developments......Page 185 Suggested Reading......Page 186 9.2.1 Protein......Page 188 9.2.4 Micronutrients......Page 189 9.2.6 Nutritional Requirements in Xenobiotic Metabolism......Page 190 9.3.1 Development......Page 191 9.3.2 Gender Differences......Page 193 9.3.3 Hormones......Page 194 9.3.5 Disease......Page 196 9.4 Comparative and Genetic Effects......Page 197 9.4.1 Variations Among Taxonomic Groups......Page 198 9.4.3 Genetic Differences......Page 206 9.5 Chemical Effects......Page 209 9.5.1 Inhibition......Page 210 9.5.2 Induction......Page 215 9.6 Environmental Effects......Page 224 Suggested Reading......Page 226 10.1 Introduction......Page 228 10.3 Renal Elimination......Page 230 10.4 Hepatic Elimination......Page 232 10.4.1 Entero-hepatic Circulation......Page 233 10.4.2 Active Transporters of the Bile Canaliculus......Page 234 10.6 Conclusion......Page 235 Suggested Reading......Page 236 IV Toxic Action......Page 238 11.2 Acute Exposure and Effect......Page 240 11.3 Dose-response Relationships......Page 242 11.4 Nonconventional Dose-response Relationships......Page 244 11.5.2 Acetylcholinesterase Inhibition......Page 245 11.5.3 Ion Channel Modulators......Page 247 11.5.4 Inhibitors of Cellular Respiration......Page 248 Suggested Reading......Page 249 12.1 General Aspects of Cancer......Page 250 12.2.1 Causes, Incidence, and Mortality Rates of Human Cancer......Page 253 12.2.2 Known Human Carcinogens......Page 256 12.2.3 Classification of Human Carcinogens......Page 258 12.3 Classes of Agents Associated with Carcinogenesis......Page 261 12.3.1 DNA-Damaging Agents......Page 262 12.3.2 Epigenetic Agents......Page 264 12.4 General Aspects of Chemical Carcinogenesis......Page 265 12.5 Initiation-Promotion Model for Chemical Carcinogenesis......Page 266 12.6 Metabolic Activation of Chemical Carcinogens and DNA Adduct Formation......Page 268 12.7.1 Mutational Activation of Proto-oncogenes......Page 270 12.7.2 Ras Oncogene......Page 271 12.8.2 p53 Tumor Suppressor Gene......Page 272 12.9 General Aspects of Mutagenicity......Page 273 12.10 Usefulness and Limitations of Mutagenicity Assays for the Identification of Carcinogens......Page 274 Suggested Reading......Page 275 13.2 Principles of Teratology......Page 276 13.3 Mammalian Embryology Overview......Page 277 13.4 Critical Periods......Page 280 13.5.3 Diethylstilbestrol (DES)......Page 281 13.6 Testing Protocols......Page 282 13.6.2 International Conference of Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)-US FDA, 1994......Page 283 Suggested Reading......Page 284 V Organ Toxicity......Page 286 14.1.2 Liver Function......Page 288 14.3.1 Fatty Liver......Page 289 14.3.5 Cirrhosis......Page 291 14.3.8 Carcinogenesis......Page 292 14.4 Mechanisms of Hepatotoxicity......Page 293 14.5.1 Carbon Tetrachloride......Page 294 14.5.3 Bromobenzene......Page 295 14.5.4 Acetaminophen......Page 296 Suggested Reading......Page 297 15.1.2 Function of the Renal System......Page 298 15.2 Susceptibility of the Renal System......Page 299 15.3.1 Metals......Page 300 15.3.3 Amphotericin B......Page 301 15.3.5 Hexachlorobutadiene......Page 302 Suggested Reading......Page 303 16.2 The Nervous system......Page 304 16.2.1 The Neuron......Page 305 16.2.2 Neurotransmitters and their Receptors......Page 307 16.2.3 Glial Cells......Page 308 16.2.4 The Blood-Brain Barrier......Page 309 16.2.5 The Energy-Dependent Nervous System......Page 310 16.3 Toxicant Effects on the Nervous System......Page 311 16.3.1 Structural Effects of Toxicants on Neurons......Page 312 16.3.2 Effects of Toxicants on Other Cells......Page 314 16.3.3 Toxicant-Mediated Alterations in Synaptic Function......Page 315 16.4.1 In vivo Tests of Human Exposure......Page 318 16.4.2 In vivo Tests of Animal Exposure......Page 320 16.4.3 In vitro Neurochemical and Histopathological End Points......Page 321 Suggested Reading......Page 322 17.2 Endocrine System......Page 324 17.2.1 Nuclear Receptors......Page 327 17.2.2 Membrane-Bound Steroid Hormone Receptors......Page 329 17.3.1 Hormone Receptor Agonists......Page 331 17.3.2 Hormone Receptor Antagonists......Page 333 17.3.3 Organizational versus Activational Effects of Endocrine Toxicants......Page 334 17.3.5 Inducers of Hormone Clearance......Page 335 17.4.1 Organizational Toxicity......Page 336 17.4.2 Activational Toxicity......Page 337 17.4.3 Hypothyroidism......Page 338 17.5 Conclusion......Page 339 Suggested Reading......Page 340 18.1.3 Function......Page 342 18.3.1 Irritation......Page 345 18.3.6 Cancer......Page 346 18.4.2 Monocrotaline......Page 347 18.4.3 Ipomeanol......Page 348 18.5 Defense Mechanisms......Page 349 Suggested Reading......Page 350 19.2 The Immune System......Page 352 19.3 Immune Suppression......Page 355 19.4 Classification of Immune-Mediated Injury (Hypersensitivity)......Page 360 19.5 Effects of Chemicals on Allergic Disease......Page 361 19.5.1 Allergic Contact Dermatitis......Page 362 19.5.2 Respiratory Allergens......Page 363 19.5.3 Adjuvants......Page 365 19.6 Emerging Issues: Food Allergies, Autoimmunity, and the Developing Immune System......Page 366 Suggested Reading......Page 367 20.2 Male Reproductive Physiology......Page 368 20.3.1 General Mechanisms......Page 369 20.3.5 Effects on Endocrine Function......Page 370 20.4 Female Reproductive Physiology......Page 371 20.5.1 Tranquilizers, Narcotics, and Social Drugs......Page 372 20.5.5 Effects on Sexual Behavior......Page 373 Suggested Reading......Page 374 VI Applied Toxicology......Page 376 21.1 Introduction......Page 378 21.2.1 Introduction......Page 380 21.2.2 Routes of Administration......Page 381 21.5 In vivo Tests......Page 383 21.5.1 Acute and Subchronic Toxicity Tests......Page 384 21.5.2 Chronic Tests......Page 395 21.5.3 Reproductive Toxicity and Teratogenicity......Page 396 21.5.4 Special Tests......Page 403 21.6.2 Prokaryote Mutagenicity......Page 410 21.6.3 Eukaryote Mutagenicity......Page 412 21.6.4 DNA Damage and Repair......Page 414 21.6.5 Chromosome Aberrations......Page 415 21.6.6 Mammalian Cell Transformation......Page 417 21.7 Ecological Effects......Page 418 21.7.2 Simulated Field Tests......Page 419 21.9 The Future of Toxicity Testing......Page 420 Suggested Reading......Page 421 22.2 Foundations of Forensic Toxicology......Page 424 22.4 Investigation of Toxicity-Related Death/Injury......Page 425 22.4.2 Considerations for Forensic Toxicological Analysis......Page 426 22.4.3 Drug Concentrations and Distribution......Page 427 22.5.3 Thin-Layer Chromatography (TLC)......Page 428 22.6 Analytical Schemes for Toxicant Detection......Page 429 22.7 Clinical Toxicology......Page 430 22.7.2 Basic Operating Rules in the Treatment of Toxicosis......Page 431 22.7.3 Approaches to Selected Toxicoses......Page 432 Suggested Reading......Page 434 23.2 Legislation and Regulation......Page 436 23.2.1 Federal Government......Page 437 23.2.3 Legislation and Regulation in Other Countries......Page 441 23.3.1 Home......Page 442 23.3.2 Workplace......Page 443 23.3.3 Pollution of Air, Water, and Land......Page 444 23.4 Education......Page 445 Suggested Reading......Page 446 24.1 Introduction......Page 448 24.2.1 Hazard Identification......Page 449 24.2.2 Exposure Assessment......Page 450 24.2.3 Dose Response and Risk Characterization......Page 451 24.3 Noncancer Risk Assessment......Page 452 24.3.1 Default Uncertainty and Modifying Factors......Page 453 24.3.2 Derivation of Developmental Toxicant RfD......Page 454 24.3.4 Benchmark Dose Approach......Page 455 24.3.5 Determination of BMD and BMDL for ETU......Page 456 24.3.7 Chemical Mixtures......Page 457 24.4 Cancer Risk Assessment......Page 458 24.5 PBPK Modeling......Page 461 Suggested Reading......Page 462 VII Environmental Toxicology......Page 464 25.1 Introduction......Page 466 25.2.1 Sampling......Page 467 25.2.3 Forensic Studies......Page 471 25.2.4 Sample Preparation......Page 472 25.2.5 Separation and Identification......Page 473 25.2.6 Spectroscopy......Page 480 25.2.7 Other Analytical Methods......Page 485 Suggested Reading......Page 486 26.1 Introduction......Page 488 26.2 Environmental Persistence......Page 489 26.2.2 Biotic Degradation......Page 490 26.2.3 Nondegradative Elimination Processes......Page 491 26.3 Bioaccumulation......Page 492 26.3.1 Factors That Influence Bioaccumulation......Page 494 26.4.1 Acute Toxicity......Page 495 26.4.2 Mechanisms of Acute Toxicity......Page 496 26.4.3 Chronic Toxicity......Page 497 26.4.4 Species-Specific Chronic Toxicity......Page 498 26.4.5 Abiotic and Biotic Interactions......Page 499 Suggested Reading......Page 502 27.1 Introduction......Page 504 27.2 Sources of Toxicants to the Environment......Page 505 27.3.1 Advection......Page 508 27.3.2 Diffusion......Page 510 27.4.1 Air–Water Partitioning......Page 512 27.4.3 Lipid–Water Partitioning......Page 513 27.4.4 Particle–Water Partitioning......Page 514 27.5.1 Reversible Reactions......Page 515 27.5.2 Irreversible Reactions......Page 518 27.6 Environmental Fate Models......Page 522 Suggested Reading......Page 523 28.1 Introduction......Page 526 28.2.1 Selecting Assessment End Points......Page 528 28.2.3 Selecting Measures......Page 531 28.3 Analyzing Exposure and Effects Information......Page 532 28.3.1 Characterizing Exposure......Page 533 28.3.2 Characterizing Ecological Effects......Page 535 28.4.2 Describing Risk......Page 537 28.5 Managing Risk......Page 541 Suggested Reading......Page 542 VIII Summary......Page 544 29.1 Introduction......Page 546 29.2 Risk Management......Page 547 29.5 In vivo Toxicity......Page 548 29.8 Development of Selective Toxicants......Page 549 Glossary......Page 550 Index......Page 568
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