This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security.
Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves researchers time in quickly accessing the very latest definitive details on toxicity of specific agents used in chemical warfare as opposed to searching through thousands of journal articles. Will include the most agent-specific information on the market.
Includes detailed coverage of the most exhaustive list of agents possibly used as chemical warfare agents in one source. Section 4: Agents That Can Be Used as Weapons of Mass Destruction ? 25 chapters long. Other books on the market only include a sample selection of specific agents. Offering all possible agents detailed under one cover makes this appealing to a wider audience and saves researchers time.
The Forward will be written by Dr. Tetsuo Satoh, Chiba University, Japan. He is one of the most respected, recognizable authorities on chemical warfare agents which will set the authoritative tone for the book.
Covers risk to humans, animals and the environment equally. Researchers involved in assessing the risks involved with a possible chemical warfare attack and those who are developing response plans to such attacks must look at not only the risks to human health but to our wildlife and environment as well. The holistic approach taken in this book ensures that the researchers have ready access to the details no matter which aspect of the effects of CWA's they might be concerned with.
This groundbreaking book covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this one-of-a-kind handbook is prepared in a very user- friendly format that can easily be followed by students, teachers and researchers, as well as lay people. Stand-alone chapters on individual chemicals and major topics allow the reader to easily access required information without searching through the entire book.This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security. Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves researchers time in quickly accessing the very latest definitive details on toxicity of specific agents used in chemical warfare as opposed to searching through thousands of journal articles. Will include the most agent-specific information on the market Includes detailed coverage of the most exhaustive list of agents possibly used as chemical warfare agents in one source. Section 4: Agents That Can Be Used as Weapons of Mass Destruction ? 25 chapters long. Other books on the market only include a sample selection of specific agents. Offering all possible agents detailed under one cover makes this appealing to a wider audience and saves researchers time The Forward will be written by Dr. Tetsuo Satoh, Chiba University, Japan. He is one of the most respected, recognizable authorities on chemical warfare agents which will set the authoritative tone for the book Covers risk to humans, animals and the environment equally. Researchers involved in assessing the risks involved with a possible chemical warfare attack and those who are developing response plans to such attacks must look at not only the risks to human health but to our wildlife and environment as well. The holistic approach taken in this book ensures that the researchers have ready access to the details no matter which aspect of the effects of CWA's they might be concerned with
Front Cover 1
Handbook of Toxicology of Chemical warfare agents 4
Copyright Page 5
Dedication 6
Contents 8
List of Contributors 12
Foreword 18
SECTION I Introduction, Historical Perspective, and Epidemiology 20
CHAPTER 1 - Introduction 22
CHAPTER 2 - Historical Perspective of Chemical Warfare Agents 26
I. INTRODUCTION 26
II. THE FIRST SUSTAINED USE OFCHEMICALS AS AGENTS OF WARFARE 27
III. INITIAL COUNTERMEASURES 28
IV. EVENTS AFTER WORLD WAR I 29
V. WORLD WAR II 30
VI. POST-WORLD WAR II 31
VII. INCAPACITANTS AND TOXINS 32
VIII. RECENT EXPERIENCES 33
IX. TERRORIST USE 34
X. CONCLUDING REMARKSAND FUTURE DIRECTION 34
References 34
CHAPTER 3 - Global Impact of Chemical Warfare Agents Used Before and After 1945 36
I. INTRODUCTION 36
II. BACKGROUND 36
III. MILITARY USE OF CWs 37
IV. THE PERIOD BETWEEN WWIAND WWII 37
V. WWII 37
VI. THE PERIOD AFTER WWIIAND THE COLD WAR 39
VII. UNINTENTIONAL USE OF TOXICCHEMICALS 41
VIII. TERRORIST USE OF CW 41
IX. NEGOTIATIONS 41
X. CONCLUDING REMARKSAND FUTURE DIRECTION 42
References 42
CHAPTER 4 - The Tokyo Subway Sarin Attack: Toxicological Whole Truth 44
I. INTRODUCTION 44
II. SARIN TOXICITY AND MECHANISMOF ONSET 44
III. OVERVIEW OF THE TOKYO SUBWAYSARIN ATTACK 45
IV. EMERGENCY TREATMENTOF SARIN TOXICITY 46
V. ACUTE AND CHRONIC SYMPTOMSOF SARIN TOXICITY 48
VI. LABORATORY FINDINGS IN SARINTOXICITY 49
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 49
Acknowledgments 50
References 50
CHAPTER 5 - Epidemiology of Chemical Warfare Agents 52
I. INTRODUCTION 52
II. PRE-WORLD WAR II 52
III. WORLD WAR II 52
IV. POST-WORLD WAR II 53
V. IRAN–IRAQ WAR 54
VI. GULF WAR 1991 54
VII. TERRORISM 56
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 57
References 57
SECTION II Agents that can be Used as Weapons of Mass Destruction 60
CHAPTER 6 Organophosphate Nerve Agents 62
I. INTRODUCTION 62
II. BACKGROUND 62
III. MECHANISM OF ACTION 63
IV. TOXICITY 66
V. RISK ASSESSMENT 74
VI. TREATMENT 76
VII. CONCLUDING REMARKS ANDFUTURE DIRECTION 78
Acknowledgments 79
References 79
CHAPTER 7 Russian VX 88
I. INTRODUCTION 88
II. BACKGROUND 88
III. MECHANISMS OF ACTIONAND TOXICITY 95
IV. TOXICOMETRY AND HYGIENICREGULATIONS 103
V. PRINCIPLES OF THERAPY 103
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 104
References 106
CHAPTER 8 Mustards and Vesicants 112
I. INTRODUCTION 112
II. HISTORY AND BACKGROUND 115
III. TOXICOKINETICS 116
IV. MECHANISM OF ACTION 117
V. TOXICITY 118
VI. RISK ASSESSMENT 122
VII. TREATMENT 123
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 123
References 123
CHAPTER 9 Arsenicals: Toxicity, their Use as Chemical Warfare Agents, and Possible Remedial Measures 128
I. INTRODUCTION 128
II. BACKGROUND 128
III. ARSINE 129
IV. ORGANIC ARSENICALS 133
V. INORGANIC ARSENIC 139
VI. TREATMENT 142
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 145
References 146
CHAPTER 10 Psychotomimetic Agent BZ (3-Quinuclidinyl Benzilate) 154
I. INTRODUCTION 154
II. BACKGROUND 154
III. TOXICOKINETICS AND MECHANISMOF ACTION 154
IV. TOXICITY 156
V. RISK ASSESSMENT 157
VI. TREATMENT 158
VII. ANALYTICAL METHODS 159
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 160
References 160
CHAPTER 11 Onchidal and Fasciculins 162
I. INTRODUCTION 162
II. BACKGROUND 162
III. MECHANISM OF ACTIONAND BIOLOGICAL EFFECTS 165
IV. EXPERIMENTAL AND HUMANTOXICITY 166
V. RISK ASSESSMENT 167
VI. TREATMENT 170
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 170
Acknowledgment 170
References 170
CHAPTER 12 Riot Control Agents 172
I. INTRODUCTION 172
II. HISTORY 172
III. BACKGROUND 174
IV. MECHANISM OF ACTION 178
V. TOXICOKINETICS 179
VI. TOXICITY 180
VII. RISK ASSESSMENT 187
VIII. TREATMENT 188
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 189
References 189
CHAPTER 13 Fluoroacetate 196
I. INTRODUCTION 196
II. BACKGROUND 196
III. TOXICOKINETICS 197
IV. MECHANISM OF ACTION 198
V. TOXICITY AND RISK ASSESSMENT 207
VI. TREATMENT 209
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 210
References 211
CHAPTER 14 Strychnine 218
I. INTRODUCTION 218
II. BACKGROUND 218
III. PHARMACOKINETICSAND TOXICOKINETICS 219
IV. MECHANISM OF ACTION 220
V. TOXICITY 220
VI. RISK ASSESSMENT 222
VII. TREATMENT 222
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 223
References 223
CHAPTER 15 Superwarfarins 226
I. INTRODUCTION 226
II. BACKGROUND 226
III. CLASSIFICATIONOF SUPERWARFARINS 228
IV. TOXICOKINETICS 231
V. MECHANISM OF ACTION 231
VI. TOXICITY 231
VII. GENERAL TREATMENTRECOMMENDATIONS 234
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 236
References 237
CHAPTER 16 Thallium 244
I. INTRODUCTION 244
II. BACKGROUND 244
III. TOXICOKINETICS 244
IV. MECHANISM OF ACTION 245
V. TOXICITY 245
VI. RISK ASSESSMENT 245
VII. TREATMENT 245
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 246
References 246
CHAPTER 17 Polycyclic Aromatic Hydrocarbons: Exposure from Emission Products and from Terrorist Attacks on US Targets - Implications for Developmental Central Nervous System Toxicity 248
I. INTRODUCTION 248
II. BACKGROUND 248
III. PAH-INDUCED PHYSIOLOGICAL ANDBEHAVIORAL TOXIC MANIFESTATIONSIN ANIMAL MODELS: EARLY PAHSTUDIES WHICH IMPLICATED THE CNSAS A TARGET 251
IV. UNDERLYING MECHANISMS OF PAHNEUROTOXICITY 255
V. CONCLUDING REMARKSAND FUTURE DIRECTION 258
References 259
CHAPTER 18 PCBs, Dioxins, and Furans: Human Exposure and Health Effects 264
I. INTRODUCTION 264
II. BACKGROUND 264
III. HUMAN EXPOSURE TO PCBS, PCDDS,AND PCDFS 266
IV. PHYSICOCHEMICAL PROPERTIESAND GLOBAL DISTRIBUTION 267
V. ANALYTICAL METHODS 267
VI. MECHANISM OF ACTIONAND TOXICITY 267
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 270
References 270
CHAPTER 19 Cyanide Toxicity and its Treatment 274
I. INTRODUCTION 274
II. SOURCES OF EXPOSURE 275
III. TOXIC LEVELS OF CYANIDE 276
IV. DETECTION AND ESTIMATIONOF CYANIDE 277
V. TOXICOKINETICS OF CYANIDE 278
VI. MECHANISM OF ACTION 278
VII. DIAGNOSIS AND CLINICALFEATURES OF CYANIDE POISONING 280
VIII. TREATMENT OF CYANIDEPOISONING 280
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 283
Acknowledgment 284
References 284
CHAPTER 20 Carbon Monoxide: From Public Health Risk to Painless Killer 290
I. INTRODUCTION 290
II. HISTORICAL BACKGROUND 291
III. EPIDEMIOLOGICALCONSIDERATIONS 292
IV. TOXICOKINETICS ANDTOXICODYNAMICS 292
V. MECHANISM OF TOXICITY 296
VI. TOXICITY OF CARBON MONOXIDE 298
VII. PHYSIOLOGICAL ROLESOF CARBON MONOXIDE 301
VIII. TREATMENT OF CARBONMONOXIDE OVERDOSE 303
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 303
Acknowledgments 304
References 304
CHAPTER 21 Methyl Isocyanate: The Bhopal Gas 312
I. INTRODUCTION 312
II. BACKGROUND 312
III. THE MAKING OF A DISASTER 313
IV. TOXICOKINETICS OF ISOCYANATES 313
V. MECHANISM OF ACTION 316
VI. THE CYANIDE CONTROVERSY: MICOR HCN? 317
VII. TOXICITY OF ISOCYANATES 319
VIII. TREATMENT 324
IX. TOXIC POTENTIAL OF MIC BEYONDTHE BHOPAL DISASTER 324
X. CONCLUDING REMARKSAND FUTURE DIRECTION 325
Acknowledgments 325
References 325
CHAPTER 22 Chlorine 332
I. INTRODUCTION 332
II. HISTORICAL BACKGROUND 332
III. TOXICOKINETICS 332
IV. MECHANISM OF TOXICITY 333
V. TOXICITY 333
VI. RISK ASSESSMENT 336
VII. TREATMENT 338
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 338
References 338
CHAPTER 23 Phosgene 340
I. INTRODUCTION 340
II. BACKGROUND 340
III. TOXICOKINETICS 340
IV. MECHANISM OF ACTION 341
V. TOXICITY 341
VI. RISK ASSESSMENT 343
VII. TREATMENT 343
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 343
References 347
CHAPTER 24 Other Toxic Chemicals as Potential Chemical Warfare Agents 350
I. INTRODUCTION 350
II. GENERAL 350
III. SPECIFIC AGENTS 351
IV. NONLETHAL WEAPONS 355
V. CONCLUDING REMARKSAND FUTURE DIRECTION 356
References 356
CHAPTER 25 Ricin and Abrin 358
I. INTRODUCTION 358
II. BACKGROUND 358
III. TOXICOKINETICS 359
IV. MECHANISM OF ACTION 360
V. TOXICITY 360
VI. RISK ASSESSMENT 365
VII. TREATMENT 368
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 368
References 369
CHAPTER 26 Trichothecene Mycotoxins 372
I. INTRODUCTION 372
II. BACKGROUND 372
III. TOXICOKINETICS 374
IV. MECHANISM OF ACTION 375
V. TOXICITY 376
VI. RISK ASSESSMENT 383
VII. TREATMENT 383
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 384
References 385
CHAPTER 27 Toxins of Cyanobacteria 390
I. INTRODUCTION 390
II. BACKGROUND 390
III. STRUCTURE, MECHANISMOF ACTION, AND TOXICITYOF CYANOTOXINS 391
B. Neurotoxins 393
IV. RISK ASSESSMENT 394
V. TREATMENT 395
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 395
References 395
CHAPTER 28 Radiation and Health Effects 400
I. INTRODUCTION 400
II. BASIC RADIATION CONCEPTS 400
III. INTERACTION OF RADIATIONWITH MATTER 401
IV. ABSORBED DOSE 401
V. MECHANISMS OF DNA DAMAGEAND MUTAGENESIS 403
VI. ANIMAL EXPOSURESAND RADIATION TOXICITY 404
VII. HUMAN EXPOSURESAND RADIATION TOXICITY 406
VIII. RADIATION HORMESIS 408
IX. CONSEQUENCES OF RADIATIONTHERAPY 409
X. CONCLUDING REMARKSAND FUTURE DIRECTION 409
Acknowledgments 410
References 410
CHAPTER 29 Depleted Uranium 412
I. INTRODUCTION 412
II. BACKGROUND 412
III. EXPOSURE PATHWAYS AND BODYRETENTION OF DU 413
IV. PHARMACOKINETICS 415
V. MECHANISM OF ACTION 417
VI. TOXICITY OF DEPLETED URANIUMEXPOSURE 417
VII. TREATMENT 420
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 420
Acknowledgments 420
References 420
CHAPTER 30 Botulinum Toxin 426
I. INTRODUCTION 426
II. BACKGROUND 427
III. EPIDEMIOLOGY 430
IV. PATHOGENESIS 433
V. TOXICOKINETICS 438
VI. MECHANISM OF ACTION 439
VII. TOXICITY 442
VIII. RISK ASSESSMENT 444
IX. TREATMENT 445
X. CONCLUDING REMARKSAND FUTURE DIRECTION 446
References 447
CHAPTER 31 Anthrax 452
I. INTRODUCTION 452
II. HISTORY 452
III. EPIDEMIOLOGY 453
IV. PATHOGENESIS 454
V. TOXICOKINETICS 460
VI. MECHANISM OF TOXICITY 461
VII. TOXICITY 465
VIII. DETECTION AND DIAGNOSIS 467
IX. RISK ASSESSMENT 468
X. TREATMENT 469
XI. CONCLUDING REMARKSAND FUTURE DIRECTION 472
References 473
SECTION III Target Organ Toxicity 480
CHAPTER 32 The Nervous System as a Target for Chemical Warfare Agents 482
I. INTRODUCTION 482
II. OVERVIEW OF THE NERVOUSSYSTEM 482
III. SPECIAL FEATURESOF THE NERVOUS SYSTEM 483
IV. TYPES OF NEUROTOXICANTS 484
V. CELLULAR MAINTENANCE 485
VI. VOLTAGE-GATED ION CHANNELS 486
VII. NEUROTRANSMITTER SYSTEMS 487
VIII. SELECTED CWAS THAT AFFECTNERVOUS SYSTEM FUNCTION 489
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 493
References 493
CHAPTER 33 Behavioral Toxicity of Nerve Agents 500
I. INTRODUCTION 500
II. THE METHODS USED TO EVALUATEBEHAVIORAL EFFECTS OF NERVEAGENTS 500
III. LONG-TERM BEHAVIORAL EFFECTSOF ACUTE HIGH-LEVEL EXPOSURE TONERVE AGENTS 504
IV. CHRONIC BEHAVIORAL EFFECTSOF SINGLE OR REPEATED LOW-LEVELEXPOSURE TO NERVE AGENTS 506
V. CONCLUDING REMARKSAND FUTURE DIRECTION 508
References 508
CHAPTER 34 Cardiovascular System as a Target of Chemical Warfare Agents 512
I. INTRODUCTION 512
II. BACKGROUND 512
III. SIGNATURES OF CARDIACTOXICITY 514
IV. INDICES OF THE TOXICITYOF WARFARE AGENTS 516
V. SPECIFIC WARFARE AGENTS OFCONCERN REGARDING THE HEART 518
VI. OTHER TERROR AGENTS 521
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 523
References 523
CHAPTER 35 Skeletal Muscle 528
I. INTRODUCTION 528
II. BEHAVIORAL EFFECTS 528
III. CHOLINERGIC SYSTEM 529
IV. NONCHOLINERGIC SYSTEM 534
V. MUSCLE ACTIVITY – EMG 537
VI. MUSCLE FIBER HISTOPATHOLOGY 538
VII. MUSCLE CYTOTOXICITYBIOMARKERS 540
VIII. SKELETAL MUSCLESAND TOLERANCE DEVELOPMENT 541
IX. SKELETAL MUSCLE INVOLVEMENTIN INTERMEDIATE SYNDROME 542
X. PREVENTION/TREATMENTOF MYOPATHY 543
XI. CONCLUDING REMARKSAND FUTURE DIRECTION 546
Acknowledgments 547
References 547
CHAPTER 36 Reproductive Toxicity and Endocrine Disruption of Potential Chemical Warfare Agents 552
I. INTRODUCTION 552
II. IMPORTANT DEFINITIONSAND CONCEPTS 553
III. THE REPRODUCTIVE TOXICITYOF SELECTED TOXICANTS 556
IV. CONCLUDING REMARKSAND FUTURE DIRECTION 563
References 563
CHAPTER 37 Liver Toxicity of Chemical Warfare Agents 568
I. INTRODUCTION 568
II. STRUCTURAL ORGANIZATIONOF THE LIVER 568
III. FACTORS INFLUENCING HEPATICTOXICITY 569
IV. WARFARE AGENTS AFFECTINGLIVER 576
V. CONCLUDING REMARKSAND FUTURE DIRECTION 577
References 577
CHAPTER 38 Renal Toxicity 580
I. INTRODUCTION 580
II. RENAL ANATOMY AND PHYSIOLOGY 580
III. TOXIC EFFECTS ON THE KIDNEY 583
IV. CONCLUDING REMARKSAND FUTURE DIRECTION 591
References 591
CHAPTER 39 Ocular Toxicity of Sulfur Mustard 594
I. INTRODUCTION 594
II. BACKGROUND 594
III. OCULAR TOXICITYAND TOXICOKINETICS 597
IV. MECHANISM OF ACTION 601
V. RISK ASSESSMENT 604
VI. TREATMENTS 605
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 608
Acknowledgments 609
References 609
CHAPTER 40 Immunotoxicity 614
I. INTRODUCTION 614
II. THE IMMUNE SYSTEM 614
III. TARGETS OF IMMUNOTOXICITY 616
IV. EXPOSITION OF AUTOANTIGENSAND INTERFERENCE WITHCO-STIMULATORY SIGNALS 617
V. INDUCTION OF INFLAMMATIONAND NONCOGNATE T–B COOPERATION 617
VI. REGULATION OF THE IMMUNERESPONSE 617
VII. IMMUNOTOXICITY OF CHEMICALWARFARE AGENTS 618
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 625
References 625
CHAPTER 41 Dermal Toxicity of Sulfur Mustard 630
I. INTRODUCTION 630
II. BACKGROUND 630
III. PATHOGENESIS 631
IV. MODELS OF DERMAL SULFURMUSTARD EXPOSURE 635
V. THERAPEUTICS 639
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 642
References 642
SECTION IV Special Topics 650
CHAPTER 42 Excitotoxicity, Oxidative Stress, and NeuronalnbspInjury 652
I. INTRODUCTION 652
II. EXCITOTOXICITY ANDNEURODEGENERATION 653
III. OXIDATIVE INJURY 654
IV. LIPID PEROXIDATION AND IN VIVOMARKERS OF OXIDATIVE DAMAGE 655
V. HIGH-ENERGY PHOSPHATES 656
VI. NITRIC OXIDE (NO/NOS) 657
VII. DENDRITIC INJURY 657
VIII. ANTICHOLINESTERASE-INDUCEDSEIZURES, OXIDATIVE INJURY,AND NEURODEGENERATION 658
IX. OXIDATIVE DAMAGEAND DENDRITIC DEGENERATIONFOLLOWING KAINIC ACID-INDUCEDEXCITOTOXICITY 659
X. SUPPRESSION OF SEIZURE-INDUCEDOXIDATIVE INJURY ANDNEURODEGENERATION 661
XI. NMDA RECEPTOR ANTAGONIST(MEMANTINE) 663
XII. CONCLUDING REMARKSAND FUTURE DIRECTION 664
Acknowledgment 664
References 664
CHAPTER 43 Neuropathologic Effects of Chemical Warfare Agents 672
I. INTRODUCTION 672
II. BACKGROUND 672
III. ACUTE EFFECTS OF SYMPTOMATICEXPOSURE 673
IV. PROLONGED EFFECTSOF SYMPTOMATIC EXPOSURE 674
V. ORGANOPHOSPHATE-INDUCEDDELAYED NEUROTOXICITY (OPIDN) 676
VI. ORGANOPHOSPHATE-ASSOCIATEDMUSCLE WEAKNESS 677
VII. EFFECTS OF SUBSYMPTOMATICEXPOSURE TO NERVE AGENTS 677
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 678
References 678
CHAPTER 44 Molecular and Transcriptional Responses to Sarin Exposure 684
I. INTRODUCTION 684
II. BACKGROUND 684
III. SARIN-INDUCED CLINICALCHANGES AS A FUNCTION OFCELLULAR AND MOLECULARALTERATIONS 686
IV. CONCLUDING REMARKSAND FUTURE DIRECTION 698
References 698
CHAPTER 45 The Effects of Organophosphates in the Early Stages of Human Muscle Regeneration 702
I. INTRODUCTION 702
II. REGENERATION PROCESS IN THEHUMAN SKELETAL MUSCLE 702
III. THE EFFECTS OF DFP ON THEREGENERATION PROCESS IN THEHUMAN SKELETAL MUSCLE 703
IV. CONCLUDING REMARKSAND FUTURE DIRECTION 707
Acknowledgments 707
References 707
CHAPTER 46 Organophosphate Intoxication: Molecular Consequences, Mechanisms and Solutions 710
I. INTRODUCTION 710
II. HUMAN CHOLINESTERASES:THE COMMON CORE 710
III. HUMAN CHOLINESTERASES:MYRIAD OF MOLECULAR FORMS 711
IV. REGULATION OF AChE GENEEXPRESSION 712
V. LOCATION AND FUNCTION OF AChEIN THE NEUROMUSCULAR JUNCTION 712
VI. BUTYRYLCHOLINESTERASE AS THEINHERENT PROTECTOR OF AChE 713
VII. ACUTE TOXICITY PRODUCESSHORT-TERM LOSS OF FUNCTION 713
VIII. LONG-TERM EFFECTS OF AChE-ROVERPRODUCTION 715
IX. PREVENTION OFANTICHOLINESTERASE TOXICITY:THE ‘‘NEXT GENERATION’’ 720
X. CONCLUDING REMARKSAND FUTURE DIRECTION 726
Acknowledgments 726
References 727
SECTION V Risks to Animals and Wildlife 738
CHAPTER 47 Chemical Warfare Agents and Risks to Animal Health 740
I. INTRODUCTION 740
II. CHEMICAL WARFARE AGENTS 741
III. CONCLUDING REMARKS ANDFUTURE DIRECTION 752
References 753
CHAPTER 48 Potential Agents that Can Cause Contamination of Animal Feedstuffs and Terror 758
I. INTRODUCTION 758
II. MYCOTOXINS AND TOXIGENICFUNGI 759
III. MICROBIAL TOXINS 760
IV. PLANT TOXINS 760
V. RAPIDLY ACTING AND EASILYAVAILABLE SUBSTANCES 762
VI. PERSISTENT ORGANIC COMPOUNDS 762
VII. HEAVY METALS 763
VIII. CONTAMINATED TRANSPORTVESSELS 763
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 763
References 764
CHAPTER 49 - Threats to Wildlife by Chemical Warfare Agents 766
I. INTRODUCTION 766
II. BACKGROUND 766
III. WILDLIFE PROBLEMS OCCURRINGAFTER A TERRORIST ATTACK 766
IV. ILLICIT AND RESTRICTEDSUBSTANCES 766
V. CYANIDE 767
VI. RICIN (CASTOR BEAN) 768
VII. PESTICIDES 768
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 769
References 769
SECTION VI Toxicokinetics and Physiologically Based Pharmacokinetics 772
CHAPTER 50 Toxicokinetics of Chemical Warfare Agents: Nerve Agents and Vesicants 774
I. INTRODUCTION 774
II. Overview Of Invasion Processes Of Chemical Warfare Agents 774
III. NERVE AGENTS 778
IV. VESICANTS 793
V. CONCLUDING REMARKSAND FUTURE DIRECTION 802
References 802
CHAPTER 51 Physiologically Based Pharmacokinetic Modeling of Chemical Warfare Agents 810
I. INTRODUCTION 810
II. DEVELOPMENT OFPHYSIOLOGICALLY BASEDPHARMACOKINETIC MODELS 811
III. NEED FOR IMPROVED MEASURESOF CWNA EXPOSURES – USE OF PBPKANALYSIS OF DATA 812
IV. PBPK SIMULATION OFCHOLINESTERASE INHIBITIONAND REGENERATED GB 814
V. CONCLUDING REMARKSAND FUTURE DIRECTION 815
References 816
CHAPTER 52 Metabolism of Warfare Nerve Agents 818
I. INTRODUCTION 818
II. CHEMICAL ASPECTS OFMETABOLISM OF NERVE AGENTS 818
IV. OTHER FACTORS INVOLVEDIN METABOLISM AND DETOXIFICATIONOF NERVE AGENTS 825
V. CONCLUDING REMARKSAND FUTURE DIRECTION 826
Acknowledgments 826
References 826
SECTION VII Analytical Methods, Biosensors, and Biomarkers 830
CHAPTER 53 On-Site Detection of Chemical Warfare Agents 832
I. INTRODUCTION 832
II. PROPERTIES OF CHEMICALWARFARE AGENTS 832
III. CONCEPT OF ON-SITE DETECTION 832
IV. THE PRESENT SITUATIONOF THE DETECTION TECHNOLOGY 835
V. COMPARISON OF THE EXISTINGON-SITE DETECTION TECHNOLOGIES 840
VI. DEVELOPMENT OF NEW ON-SITEDETECTION TECHNOLOGIES 840
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 843
References 843
CHAPTER 54 Laboratory Analysis of Chemical Warfare Agents and Metabolites in Biomedical Samples 846
I. INTRODUCTION 846
II. NERVE AGENTS 846
III. SULFUR MUSTARD AND LEWISITE 851
IV. CONCLUDING REMARKS ANDFUTURE DIRECTION 851
References 852
CHAPTER 55 Biosensors for the Detection of OP Nerve Agents 856
I. INTRODUCTION 856
II. BIOSENSORS 856
III. ELECTROCHEMICAL BIOSENSORSFOR DETECTING ORGANOPHOSPHORUSCOMPOUNDS 858
IV. MISCELLANEOUS BIOSENSORS FOROP DETECTION 863
V. CONCLUDING REMARKS ANDFUTURE DIRECTION 864
References 864
CHAPTER 56 Biomarkers of Exposure to Organophosphorus Poisons: A New Motif for Covalent Binding to Tyrosine in Proteins that have No Active Site Serine 866
I. INTRODUCTION 866
II. USE OF ACETYLCHOLINESTERASEAND BUTYRYLCHOLINESTERASEBIOMARKERS IN THE CLINIC 866
III. METHODS TO DETECT OP ADDUCTSON ACETYLCHOLINESTERASE ANDBUTYRYLCHOLINESTERASE 867
IV. WHY ARE NEW BIOMARKERSNEEDED? 868
V. NEW BIOMARKERS IN ANIMALS 871
VI. COVALENT BINDING OF OPTO TYROSINE 871
VII. MOTIF FOR OP BINDINGTO TYROSINE 872
VIII. CHARACTERISTICS OF OP BINDINGTO TYROSINE 872
IX. METHODS FOR DETECTING OPBINDING TO TYROSINE 875
X. CONCLUDING REMARKSAND FUTURE DIRECTION 875
Acknowledgments 875
References 875
CHAPTER 57 Biomarkers and Biosensors of Delayed Neuropathic Agents 878
I. INTRODUCTION 878
II. OP COMPOUNDS 878
III. OPIDN 879
IV. NTE 880
V. KINETICS OF OP INHIBITOR–SERINEHYDROLASE INTERACTIONS 882
VI. BIOMARKERS 886
VII. BIOSENSORS 888
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 891
References 891
CHAPTER 58 Monitoring of Blood Cholinesterase Activity in Workers Exposed to Nerve Agents 896
I. INTRODUCTION 896
II. DETERMINATION OFCHOLINESTERASES 896
III. FACTORS INFLUENCING ACTIVITYOF CHOLINESTERASES 898
IV. DIAGNOSIS OF OP POISONING 898
V. MONITORING OF BLOODCHOLINESTERASE ACTIVITYIN WORKERS WITH NERVE AGENTS 900
VI. CONCLUDING REMARKS ANDFUTURE DIRECTION 902
Acknowledgments 902
References 902
SECTION VIII Prophylactic, Therapeutic, and Countermeasures 906
CHAPTER 59 Strategies to Enhance Medical Countermeasures After the Use of Chemical Warfare Agents on Civilians 908
I. INTRODUCTION 908
II. SCOPE OF RESEARCH 908
III. COUNTERACT PROGRAMSTRUCTURE 909
IV. THE CIVILIAN THREAT SPECTRUMAND SPECIAL CONCERNS 909
V. PRETREATMENTS 910
VI. POST-EXPOSURE PRE-TARGETPROPHYLACTIC THERAPIES 911
VII. POST-EXPOSURE POST-TARGETTREATMENT 911
VIII. DIAGNOSTIC TECHNOLOGIES 912
IX. BASIC/MECHANISTIC RESEARCHAND TARGET IDENTIFICATION 912
X. IN VITRO AND ANIMAL MODELSFOR EFFICACY SCREENING 912
XI. ADVANCED PRECLINICALDEVELOPMENT AND CLINICAL STUDIES 913
XII. CONCLUDING REMARKSAND FUTURE DIRECTION 913
References 913
CHAPTER 60 Medical Countermeasures and Other Therapeutic Strategies for Sulfur Mustard Toxicity 916
I. INTRODUCTION 916
III. TREATMENT OF SKIN INJURIES 919
II. SKIN DECONTAMINATION 917
IV. TREATMENT OF LUNG LESIONS 922
V. TREATMENT OF EYE LESIONS 924
VI. TREATMENT OF SYSTEMIC EFFECTS 924
VII. SM-INDUCED OXIDATIVE STRESSAND ITS PROTECTION 927
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 931
References 931
CHAPTER 61 Medical Management of Chemical Toxicity in Pediatrics 938
I. INTRODUCTION 938
II. BACKGROUND 938
III. HISTORY OF PEDIATRIC CHEMICALCASUALTIES 939
IV. CHALLENGES TO MANAGINGPEDIATRIC CHEMICAL CASUALTIES 940
V. EFFECTS OF SPECIFIC AGENTS 945
VI. DECONTAMINATION OF CHILDREN 963
VII. PREPARATION FOR ACHEMICAL EVENT 964
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 966
References 966
CHAPTER 62 Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling of Countermeasures to Nerve Agents 970
I. INTRODUCTION 970
II. BACKGROUND 970
III. CURRENT COUNTERMEASURES 971
IV. NOVEL COUNTERMEASURES 972
V. PBPK/PD MODELING 973
VI. DEVELOPMENT OF PBPK/PDMODELS 973
VII. EXPERIMENTAL ANDQUANTITATIVE STRUCTURE–ACTIVITYRELATIONSHIP (QSAR)METHODOLOGIES TO PREDICT BLOODAND TISSUE PARTITION COEFFICIENTS 974
VIII. INTERACTION PBPK/PD MODELFOR NAs AND COUNTERMEASURES 976
IX. HEALTH EFFECTS ASSESSMENT ANDCOUNTERMEASURE OPTIMIZATION 979
X. CONCLUDING REMARKSAND FUTURE DIRECTION 979
References 980
CHAPTER 63 Prophylactic and Therapeutic Measures in Nerve Agent Poisoning 984
1. INTRODUCTION 984
II. BACKGROUND 984
III. MECHANISM OF ACTION 984
IV. PROPHYLACTIC MEASURES 985
V. THERAPEUTIC MEASURES 988
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 991
References 992
CHAPTER 64 Pharmacological Prophylaxis Against Nerve Agent Poisoning: Experimental Studies and Practical Implications 996
I. INTRODUCTION 996
II. PROTECTION OF AChE AGAINSTINHIBITION 996
III. SCAVENGERS 997
IV. PROPHYLAXIS WITH CURRENTANTIDOTES 998
V. PROPHYLACTIC USE OFOTHER DRUGS 998
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 1000
Acknowledgment 1000
References 1000
CHAPTER 65 Pyridinium Oximes as Cholinesterase Reactivators in the Treatment of OP Poisoning 1004
I. INTRODUCTION 1004
II. INTERACTION OFCHOLINESTERASES WITHORGANOPHOSPHATES 1004
III. CLINICAL ASPECTS OF ACUTE OPPOISONING 1005
IV. ANTIDOTES IN THE TREATMENTOF OP POISONING 1006
V. PYRIDINIUM OXIMES USED IN THETREATMENT OF POISONING WITHNERVE AGENTS AND THEIR EFFICACY 1009
VI. EFFICACY OF PYRIDINIUM OXIMESIN POISONING WITH OP PESTICIDES 1011
VII. CONCLUDING REMARKSAND FUTURE DIRECTION 1011
Acknowledgment 1012
References 1012
CHAPTER 66 Novel Oximes 1016
I. INTRODUCTION 1016
II. ORGANOPHOSPHORUSACETYLCHOLINESTERASE INHIBITORS 1016
III. ACETYLCHOLINESTERASE(AChE EC 3.1.1.7)1017
IV. ANTIDOTES FOR AChE INHIBITINGORGANOPHOSPHORUS POISONING 1018
V. SYNTHESIS OF NEW AChEINHIBITORS 1019
VI. IN VITRO EVALUATION OFSELECTED AChE REACTIVATORS 1028
VII. STRUCTURE–ACTIVITYRELATIONSHIP OF AChEREACTIVATORS 1028
VIII. PROMISING OXIMES 1034
IX. NEW TRENDS IN DEVELOPMENTOF NEW AChE REACTIVATORS 1034
X. CONCLUDING REMARKSAND FUTURE DIRECTION 1036
Acknowledgments 1036
References 1036
CHAPTER 67 Paraoxonase (PON1) and Detoxication of Nerve Agents 1042
I. INTRODUCTION 1042
II. PON1 POLYMORPHISMS: DEFININGPON1 STATUS 1042
III. PON1 AND THE TOXICITYOF OP INSECTICIDES 1043
IV. PON1 AND THE TOXICITY OF NERVEAGENTS 1045
V. PON1 AS A THERAPEUTIC AGENT 1046
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 1047
Acknowledgments 1047
References 1047
CHAPTER 68 Role of Carboxylesterases in Therapeutic Intervention of Nerve Gas Poisoning 1052
I. INTRODUCTION 1052
II. ENZYMOLOGY 1052
III. ORIGIN OF PLASMACARBOXYLESTERASE 1054
IV. ROLE OF PLASMACARBOXYLESTERASE 1055
V. CONCLUDING REMARKSAND FUTURE DIRECTION 1057
References 1058
CHAPTER 69 Protection of Acetylcholinesterase from Organophosphates: Kinetic Insight into Bioscavengers 1060
I. INTRODUCTION 1060
II. PROTECTIVE BIOSCAVENGERS 1060
III. DEVELOPMENT OF ATOXICOKINETIC PROTECTION ASSAY 1064
IV. KINETIC RELEVENCE – EFFICACYIN PROTECTION 1066
V. CONCLUDING REMARKSAND FUTURE DIRECTION 1068
Acknowledgment 1068
References 1068
CHAPTER 70 Catalytic Bioscavengers: The Next Generation of Bioscavenger-Based Medical Countermeasures 1072
I. INTRODUCTION 1072
II. STOICHIOMETRIC SCAVENGERS 1072
III. CATALYTIC SCAVENGERS 1074
IV. REQUIREMENTS 1074
V. POTENTIAL ENZYMES 1075
VI. CONCLUDING REMARKSAND FUTURE DIRECTION 1079
Acknowledgments 1079
References 1079
SECTION IX Decontamination of Chemical Warfare Agents 1086
CHAPTER 71 Rapid Decontamination of Chemical Warfare Agents 1088
I. INTRODUCTION 1088
II. THE NATURE OF HUMAN SKIN 1088
III. ORGANOPHOSPHATE NERVEAGENTS 1089
IV. VESICATING AGENTS (DISTILLEDSULFUR MUSTARD, HD IMPURE SULFURMUSTARD, H LEWISITE, L)1090
V. MODEL SYSTEMS TO MEASUREABSORPTION, REMOVAL,AND DECONTAMINATION 1091
VI. DECONTAMINATIONREQUIREMENTS 1091
VIII. CONCLUDING REMARKSAND FUTURE DIRECTION 1097
References 1098
CHAPTER 72 Detoxification of Arsenic 1102
I. INTRODUCTION 1102
II. ARSENIC IN THE ENVIRONMENT 1102
III. BIOLOGICAL PROPERTIESOF ARSENIC 1103
IV. MICROBIAL TRANSFORMATIONSOF ARSENIC 1104
V. GENES ASSOCIATED WITH ARSENICRESISTANCE MECHANISM 1110
VI. ENHANCED ARSENICACCUMULATION IN BACTERIAL CELLS 1112
VII. PROTEINS INVOLVED IN ARSENICRESISTANCE 1113
VIII. POTENTIAL APPLICATIONFOR BIOREMEDIATION OFCONTAMINATED SITES 1113
IX. CONCLUDING REMARKSAND FUTURE DIRECTION 1114
References 1114
Index 1120
Color Plate 1168
| Erscheint lt. Verlag | 2.4.2009 |
|---|---|
| Sprache | englisch |
| Themenwelt | Natur / Technik ► Fahrzeuge / Flugzeuge / Schiffe ► Militärfahrzeuge / -flugzeuge / -schiffe |
| Studium ► 2. Studienabschnitt (Klinik) ► Pharmakologie / Toxikologie | |
| Studium ► Querschnittsbereiche ► Prävention / Gesundheitsförderung | |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Biologie ► Ökologie / Naturschutz | |
| Sozialwissenschaften ► Politik / Verwaltung | |
| Technik ► Umwelttechnik / Biotechnologie | |
| ISBN-10 | 0-08-092273-2 / 0080922732 |
| ISBN-13 | 978-0-08-092273-7 / 9780080922737 |
| Haben Sie eine Frage zum Produkt? |
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