Despite ongoing efforts to prohibit the production, storage and use of chemical warfare agents recent world events highlight the enduring threat to the population from these agents. Research efforts in various countries have resulted in novel insights into chemical warfare toxicology that has enabled the development of new approaches for the diagnosis and treatment of chemical warfare poisoning. This book provides an up-to-date treatise on the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning. Focussing on the most important representative nerve and blistering agents, whilst also covering other potential chemical warfare agents, this book will give the reader a comprehensive overview of the many different aspects of chemical warfare agent toxicology. The text will appeal to toxicologists, biochemists and weapons specialists working in industry and academia, and anyone with an interest in chemical warfare toxicology or exposure.

lgli/K:\_add\3\RSC\Chemical Warfare Toxicology, Volume 2.pdf

lgrsnf/K:\_add\3\RSC\Chemical Warfare Toxicology, Volume 2.pdf

nexusstc/Chemical Warfare Toxicology/83c82c20a37e80dcbfa5cb0266c94005.pdf

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Chemical Warfare Toxicology: Volume 2: Management of Poisoning (Issues in Toxicology, Volume 27)

Chemical warfare toxicology. Volume 1., Fundamental aspects. Volume 2., Management of poisoning

Chemical Warfare Toxicology: Volume 1: Fundamental Aspects (Issues in Toxicology, Volume 26)

Chemical Warfare Toxicology: Complete Set

Franz Worek; John Jenner; Chris Timperley; Robin Black; Jonathan David; Jeffery Gearhart; Bronwen Jugg; Kai Kehe; Patrick Masson; Helen Mumford; Daan Noort; Robert Read; Doug Somerville; Dirk Steinritz; John Tattersall; Horst Thiermann

Franz Worek; John Jenner, (Of Defence Science and Technology Laboratory (Great Britain)); Horst Thiermann

Robert Read, Kai Kehe, Franz Worek, Franz Worek, Doug Somerville

Franz Worek, Robert Read, Jonathan David, Doug Somerville

Franz S Worek; John Jenner; Horst Thiermann

Worek, Franz,Jenner, John,Thiermann, Horst

Horst Thiermann, John Jenner, Franz Worek

Adobe InDesign CS6 (Windows)

Aristotle Papanikolaou

Thomas Westover

Royal Society of Chemistry, The; Royal Society of Chemistry

Ingram Publisher Services UK- Academic

Issues in toxicology (Print), No 27, Cambridge, UK, 2016

Issues in toxicology, 26 & 27, Cambridge, England, 2016

Issues in Toxicology Ser, Cambridge, LaVergne, May 2016

Lightning Source Inc. (Tier 3), Cambridge, UK, 2016

Issues in toxicology, no. 26, Cambridge, cop. 2016

Issues in toxicology, no. 27, Cambridge, cop. 2016

United Kingdom and Ireland, United Kingdom

1, 2016-05-17

1, 20160506

1, PS, 2016

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lg1593891

producers:
Adobe Acrobat 8.1

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Chemical Warfare Toxicology, Volume 2: Management of Poisoning, 2016, pp. 346, 978-1-78262-807-1
Cover 1
Chemical Warfare Toxicology Volume 2: Management of Poisoning 2
Preface 8
References to Material in The National Archives 10
Contents 12
Chapter 1 - Treatment of Nerve Agent Poisoning 22
1.1 Introduction 22
1.2 OP Compounds 23
1.2.1 General Remarks That Are Relevant for Therapy 23
1.2.2 Toxicology of OP Compounds 24
1.2.2.1 Toxicokinetic Aspects Relevant for Therapy 24
1.2.2.2 Toxicodynamics of Nerve Agents 25
1.2.2.2.1
Reactions of Nerve Agents with AChE.OP compounds, i.e. nerve agents and pesticides, inhibit serine esterases such as AChE (E.C. ... 25
1.2.2.2.2
Binding of Nerve Agents to Other Targets.As highly reactive compounds, nerve agents are able to interact with a variety of prote... 26
1.3 Protective Measures and Decontamination 27
1.4 Clinical Picture of Nerve Agent Poisoning 29
1.4.1 Acute Nerve Agent Poisoning 29
1.4.1.1 Central Nervous System 29
1.4.1.2 Autonomic Nervous System 29
1.4.1.2.1
Sympathetic Nervous System.Nicotinic ACh receptors are located at paravertebral sympathetic ganglions. In response to the pregan... 29
1.4.1.2.2
Parasympathetic Nervous System.ACh is the primary neurotransmitter of the parasympathetic nervous system and neurotransmission o... 30
1.4.1.3 Somatic Nervous System 30
1.4.1.4 Conclusion 30
1.4.2 Intermediate Syndrome 31
1.4.3 Organophosphate Induced Delayed Neuropathy 31
1.5 Pretreatment 31
1.6 Differences Between Nerve Agent and OP Compound Pesticide Poisoning 32
1.7 Therapeutic Regimen of Nerve Agent Poisoning 33
1.7.1 General Considerations 33
1.7.2 Atropine 33
1.7.2.1 Self and Buddy Aid 34
1.7.2.2 Treatment by Medical Specialists 35
1.7.3 Oximes 37
1.7.3.1 General Background 37
1.7.3.2 Effectiveness of Oximes in Nerve Agent Poisoning 38
1.7.3.3 Interaction with Persisting Poison Load 41
1.7.3.4 Oxime Dosing Strategies 42
1.7.3.5 Monitoring of Oxime Therapy 43
1.7.3.6 Obidoxime 43
1.7.3.7 Pralidoxime 45
1.7.3.8 HI-6 46
1.7.3.9 Benzodiazepines 47
1.7.3.10 Magnesium 48
1.7.3.11 Alkalinization by Sodium Bicarbonate 50
1.7.3.12 Supportive Treatment 51
1.8 Summary and Outlook 51
References 52
Chapter 2 - Nerve Agents: Catalytic Scavengers as an Alternative Approach for Medical Countermeasures 64
2.1 Introduction 64
2.2 The Scavenger Concept 65
2.3 Endogenous Bioscavengers 67
2.4 Stoichiometric Scavengers 67
2.5 Pseudo-Catalytic Scavengers 69
2.6 Catalytic Scavengers 70
2.7 Requirements for Operational Catalytic Scavengers 70
2.8 Potential Enzymes 73
2.8.1 Phosphotriesterases 73
2.8.1.1 Bacterial PTEs 73
2.8.1.2 Human Paraoxonase 75
2.8.1.3 Other Mammalian PTEs 76
2.8.2 Engineered ChEs and CaEs 77
2.8.3 Oxidases 80
2.8.3.1 Glutathione S-Transferases 80
2.8.3.2 Laccases 80
2.9 Catalytic Antibodies 81
2.10 Artificial Enzymes 81
2.11 Future Directions 81
References 83
Chapter 3 - Nicotinic Receptors as Targets for Nerve Agent Therapy 103
3.1 Introduction 103
3.2 Current Therapy for Nerve Agent Poisoning 104
3.3 Potential Benefits of Nicotinic Antagonists in Nerve Agent Poisoning 105
3.4 Nicotinic ACh Receptors 106
3.5 The Muscle nAChR 107
3.6 Blockers of Neuromuscular Transmission 110
3.7 Effects of AChE Inhibitors at the NMJ 113
3.8 Anti-Nicotinic Effects of Oximes 114
3.9 Optimisation of the Anti-Nicotinic Properties of Bispyridinium Compounds 115
3.10 Protection Against Delayed Respiratory Failure 118
3.11 Neuronal Nicotinic Receptors 119
3.12 Drugs Acting at Neuronal Nicotinic Receptors 122
3.13 Neuronal Nicotinic Effects in Nerve Agent Poisoning 123
3.13.1 Mecamylamine 123
3.13.2 Benthiactzine 124
3.14 Summary 124
References 125
Chapter 4 - Mustard: Pathophysiology and Therapeutic Approaches 141
4.1 Introduction 141
4.2 Chemistry 142
4.3 Toxicokinetics 142
4.4 Clinical Picture 145
4.4.1 Skin 145
4.4.2 Lungs 146
4.4.3 Eyes 146
4.5 Therapeutic Interventions for SM Injury in Correlation with the Molecular Pathology 147
4.5.1 Search for Novel Therapies, the Animal Efficacy Rule, Regulatory Requirements and Their Effect on Research Strategies 149
4.5.2 Alkylation 150
4.5.3 Direct SM Scavengers 152
4.5.4 Inflammation 152
4.5.5 Anti-Inflammatory Therapy 153
4.5.6 Repair of SM Induced DNA Lesions with a Focus on PARP 154
4.5.7 PARP Inhibitors 155
4.5.8 SM and Cell Death 156
4.5.9 Limitation of Extrinsic Apoptosis 158
4.5.10 Reactive Species Formation After SM Exposure 158
4.5.11 Anti-Oxidative Interventions 159
4.5.12 Other Therapeutic Approaches 161
4.5.12.1 Macrolide Antibiotics 161
4.5.12.2 Silibinin 163
4.5.12.3 Phytopharmaceuticals 164
4.5.12.4 Cell Therapies 165
4.6 Summary and Outlook 166
References 167
Chapter 5 - Clinical and Laboratory Diagnosis of Chemical Warfare Agent Exposure 178
5.1 Introduction 178
5.2 Structure and Mechanism 179
5.3 Clinical Diagnosis 180
5.3.1 Clinical Signs of Nerve Agent Poisoning 181
5.3.2 Clinical Signs After Exposure to Volatile Nerve Agents 182
5.3.3 Clinical Signs After Exposure to Low Volatility Nerve Agents 183
5.3.4 Alternative Indicators of Nerve Agent Exposure 185
5.4 Laboratory Diagnosis 185
5.4.1 Cholinesterases as Diagnostic Markers 186
5.4.2 Onsite Determination of Cholinesterase Activity 187
5.4.3 Therapeutic Monitoring: The Cholinesterase Status 189
5.5 Summary and Outlook 192
References 193
Chapter 6 - Verification of Exposure to Chemical Warfare Agents 200
6.1 Introduction 200
6.2 Biomarkers of Exposure 201
6.2.1 Analytical Methods and Instrumentation 203
6.3 Sulphur Mustard 205
6.3.1 Application to Human Samples 206
6.3.1.1 Intact Agent and Metabolites 206
6.3.1.2 Protein and DNA Adducts 212
6.3.1.3 Recent Human Exposures to Sulphur Mustard 214
6.4 Nerve Agents 215
6.4.1 Application to Human Samples 221
6.4.1.1 Samples from Japanese Casualties of Sarin Exposure 222
6.4.1.2 Sample from a Japanese Casualty of VX Exposure 224
6.4.1.3 Samples from an Accidental VX Exposure 225
6.5 Other Agents 226
6.5.1 Analogues of Sulphur Mustard 226
6.5.2 Nitrogen Mustards 226
6.5.3 Lewisite 227
6.5.4 Quinuclidinyl Benzilate 228
6.5.5 Phosgene and Hydrogen Cyanide 228
6.6 Further Developments 229
References 229
Chapter 7 - The Impact of New Technologies on the Elucidation of Chemical Warfare Agent Toxicology 240
7.1 Introduction 240
7.2 Transcriptomics 241
7.2.1 The Use of Microarrays to Study CWA Toxicology 242
7.2.1.1 Nerve Agents 244
7.2.1.2 Vesicants 247
7.2.1.3 Toxic Industrial Chemicals 250
7.2.1.4 Toxins 251
7.2.2 Alternative RNA Based Approaches 252
7.2.2.1 RNA Sequencing Transcriptomics 252
7.2.2.2 RNA Interference 253
7.2.3 Transcriptomics Conclusion 254
7.3 Proteomics 255
7.3.1 The Principle Strategy of Proteomics 255
7.3.2 Two-Dimensional Gel Electrophoresis 256
7.3.3 Mass Spectrometry 257
7.3.3.1 Matrix Assisted Laser Desorption/Ionisation Mass Spectrometry 257
7.3.3.2 Electrospray Ionisation Mass Spectrometry 259
7.3.4 Special Analytical Feature for Relative or Absolute Protein/Peptide Quantification 259
7.3.4.1 Stable Isotope Labelling by Amino Acids in Cell Culture 260
7.3.4.2 Isobaric Tagging for Relative and Absolute Quantification 260
7.3.5 Proteomic Research of CWAs 262
7.3.5.1 Organophosphorus Agents 262
7.3.5.2 HD and Alkylating Agents 263
7.3.5.3 Protein Adducts as Biomarkers 264
7.3.6 Proteomics Conclusion 265
7.4 In silico Approaches 266
7.5 Overall Conclusion 268
References 269
Chapter 8 - Chemical Defence Against Fentanyls 280
8.1 Introduction 280
8.2 Brief History 281
8.3 Medicinal Uses 284
8.4 Military Interest 286
8.5 Illegal Trade 288
8.6 Moscow Theatre Siege 290
8.7 Resurgence of Military Interest 294
8.8 Biological Effects 294
8.8.1 Inhalation Toxicity 294
8.8.2 Dermal Toxicity 296
8.8.3 Opioid Antagonists 297
8.8.4 Opioid Receptors 300
8.9 Chemistry 301
8.9.1 Properties 301
8.9.2 Pyrolysis 302
8.9.3 Hydrolysis 304
8.9.4 Decontamination 306
8.9.5 Detection 310
8.10 Identification 311
8.10.1 Environmental Samples 311
8.10.2 Biomedical Samples 311
8.11 Conclusions 314
References 315
Subject Index 335

Volume 1: Fundamental Aspects. Development, Historical Use And Properties Of Chemical Warfare Agents / Robin Black -- Toxicology Of Vesicants / John Jenner -- Toxicology Of Organophosphorus Nerve Agents / Helen Rice -- Toxicology And Treatment Of Phosgene Induced Lung Injury / Bronwen Jugg -- Human Exposures To Sulfur Mustard / John Jenner -- Long-term Effects Of The Chemical Warfare Agent Sulfur Mustard / Kai Kehe, Dirk Steinritz, Frank Balszuweit, And Horst Thiermann -- Toxicokinetics Of Sulfur Mustard / Jan P. Langenberg, Marcel J. Van Der Schans, And Daan Noort -- Modeling Organophosphorus Chemical Warfare Nerve Agents: A Physiologically Based Pharmacokinetic-pharmacodynamic (pbpk-pd) Model Of Vx / Tammier R. Covington, Lucille A. Lumley, Christopher D. Ruark, Edward D. Clarkson, Christopher E. Whalley, And Jeffery M. Gearhart -- Allometric Modeling Of Mammalian Cyanogen Chloride Inhalation Lethality / Douglas R. Sommerville. Volume 2: Management Of Poisoning. Treatment Of Nerve Agent Poisoning / Horst Thiermann, Nadine Aurbek, And Franz Worek -- Nerve Agents: Catalytic Scavengers As An Alternative Approach For Medical Countermeasures / Patrick Masson -- Nicotinic Receptors As Targets For Nerve Agent Therapy / John Tattersall -- Mustard: Pathophysiology And Therapeutic Approaches / Dirk Steinritz, Frank Balszuweit, Horst Thiermann, And Kai Kehe -- Clinical And Laboratory Diagnosis Of Chemical Warfare Agent Exposure / Franz Worke, Horst Thiermann, And Timo Wille -- Verification Of Exposure To Chemical Warfare Agents / Robert W. Read -- The Impact Of New Technologies On The Elucidation Of Chemical Warfare Agent Toxicology / Jonathan David And Harald John -- Chemical Defence Against Fentanyls / Christopher D. Lindsay, James R. Riches, Neil Roughley, And Christopher M. Timperley. Edited By Franz Worek, Bundeswehr Institute Of Pharmacology And Toxicology, Munich, Germany, John Jenner, Defence Science And Technology Laboratory, Porton Down, Uk, Horst Thiermann, Bundeswehr Institute Of Pharmacology And Toxicology, Munich, Germany. Includes Bibliographical References And Index. Mode Of Access: World Wide Web.

Despite ongoing efforts to prohibit the production, storage and use of chemical warfare agents recent world events highlight the enduring threat to the population from these agents. Research efforts in various countries have resulted in novel insights into chemical warfare toxicology that has enabled the development of new approaches for the diagnosis and treatment of chemical warfare poisoning. This book provides an up-to-date treatise on the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning. Focusing on the most important representative nerve and blistering agents, whilst also covering other potential chemical warfare agents, this book will give the reader a comprehensive overview of the many different aspects of chemical warfare agent toxicology. The text will appeal to toxicologists, biochemists and weapons specialists working in industry and academia, and anyone with an interest in chemical warfare toxicology or exposure. -- Provided by publisher

Despite ongoing efforts to prohibit the production, storage and use of chemical warfare agents recent world events highlight the enduring threat to the population from these agents. Research efforts in various countries have resulted in novel insights into chemical warfare toxicology that has enabled the development of new approaches for the diagnosis and treatment of chemical warfare poisoning. This book provides an up-to-date treatise on the ongoing research into the toxicology of chemical warfare agents, the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning. Focussing on the fundamentals of the toxicology of nerve agents and vesicants, this book will give the reader a comprehensive overview of the many different aspects of chemical warfare agent toxicology. The text will appeal to toxicologists, biochemists and weapons specialists working in industry and academia, and anyone with an interest in chemical warfare toxicology or exposure.

2016-12-07