Handbook of Toxicology of Chemical Warfare Agents - 2nd Edition - ISBN: 9780128001592, 9780128004944

Handbook of Toxicology of Chemical Warfare Agents

2nd Edition

Editors: Ramesh C. Gupta
eBook ISBN: 9780128004944
Hardcover ISBN: 9780128001592
Imprint: Academic Press
Published Date: 21st January 2015
Page Count: 1198
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Description

Handbook of Toxicology of Chemical Warfare Agents, Second Edition covers every aspect of deadly toxic chemicals used in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this essential reference offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors and biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, and countermeasures.

Expanding on the ground-breaking first edition, Handbook of Toxicology of Chemical Warfare Agents has been completely updated, presenting the most recent advances in field. Brand new chapters include a case study of the Iran-Iraq war, an overview of chemical weapons of mass destruction, explosives, ricin, the human respiratory system, alternative testing methods, brain injuries, and more.

Key Features

  • Unites world-leading experts to present cutting-edge, agent-specific information on chemical warfare agents and their adverse effects on human and animal health and the environment.
  • Covers all aspects of chemical warfare agent modes of action, detection, prevention, therapeutic treatment and countermeasures.
  • Features a full update on the first edition to reflect the most recent advances in the field as well as nine new chapters.

Readership

Toxicologists, defence scientists, homeland and governmental security agents, and risk assessment specialists

Table of Contents

  • Dedication
  • List of Contributors
  • Section I: Introduction, Historical Perspective, and Epidemiology
    • Chapter 1. Introduction
    • Chapter 2. Historical Perspective of Chemical Warfare Agents
      • Introduction
      • The First Sustained Use of Chemicals as Agents of War
      • Initial Countermeasures
      • Events After World War I
      • World War II
      • Post–World War II
      • Incapacitants and Toxins
      • Recent Experience
      • Terrorist Use
      • Concluding Remarks and Future Research
      • References
    • Chapter 3. Global Impact of Chemical Warfare Agents Used Before and After 1945
      • Introduction
      • Background
      • Military use of CWs
      • The Period Between World War I and World War II
      • World War II
      • The Period after World War II and the Cold War
      • Persian Gulf War
      • Syria
      • Unintentional Use of Toxic Chemicals
      • Terrorist Use of CWs
      • Negotiations
      • Concluding Remarks and Future Direction
      • Acknowledgment
      • References
    • Chapter 4. The Tokyo Subway Sarin Attack: Acute and Delayed Health Effects in Survivors
      • Introduction
      • Sarin Toxicity and Mechanism of Onset
      • Overview of the Tokyo Subway Sarin Attack
      • Emergency Treatment of Sarin Toxicity
      • Acute and Chronic Symptoms of Sarin Toxicity
      • Long-Lasting Indefinite Complaints of Sarin-Exposed Victims
      • Laboratory Findings in Sarin Toxicity
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 5. Early and Delayed Effects of Sulfur Mustard in Iranian Veterans After the Iraq–Iran Conflict
      • Introduction
      • Summarized Historical Uses
      • Types and Routes of Exposure
      • Human Toxicity
      • Main Mechanisms of Toxicity
      • Target Organs and Acute Clinical Features
      • Hematoimmunological Complications
      • Delayed Clinical Complications
      • Respiratory Tract
      • Peripheral Neuromuscular Complications
      • Dermal Delayed Effects
      • Ophthalmologic Complications
      • Psychiatric Complications
      • Carcinogenicity
      • Reproductive
      • Cardiovascular Complications
      • Recent Advances in SM Poisoning and its Complications
      • Concluding Remarks and Future Directions
      • References
    • Chapter 6. Epidemiology of Chemical Warfare Agents
      • Introduction
      • Pre-World War II
      • World War II
      • Post-World War II
      • Iran–Iraq War
      • 1991 Gulf War
      • Terrorism
      • Concluding Remarks and Future Directions
      • References
    • Chapter 7. Chemical Weapons of Mass Destruction and Terrorism: A Threat Analysis
      • Introduction
      • CWs for Terrorist Actions
      • Extortion Activities with CWs
      • State Terrorism
      • Nationalist and Separatist Terrorist Groups
      • Left-Wing Terrorist Groups
      • Right-Wing Terrorist Groups and Lone Wolves
      • Apocalyptic Cults: Aum Shinrikyo
      • Jihadist Terrorism: Al Qaeda
      • Concluding Remarks and Future Directions
      • References
  • Section II: Agents That Can Be Used as Weapons of Mass Destruction
    • Chapter 8. Mustards and Vesicants
      • Introduction
      • History and Background
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 9. Organophosphate Nerve Agents
      • Introduction
      • Background
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 10. Russian VX
      • Introduction and Background
      • Monitoring of RVX
      • Mechanisms of Action and Principles of Therapy
      • Toxicometry and Hygienic Regulations
      • Concluding Remarks and Future Directions
      • References
    • Chapter 11. Riot Control Agents
      • Introduction
      • History
      • Background
      • Mechanism of Action
      • Toxicokinetics
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Direction
      • References
    • Chapter 12. Psychotomimetic Agent BZ (3-Quinuclidinyl Benzilate)
      • Introduction
      • Background
      • Toxicokinetics and Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Analytical Methods
      • Concluding Remarks and Future Direction
      • References
    • Chapter 13. Neurological Effects and Mechanisms of Blast Overpressure Injury
      • Introduction
      • Blast Waves and Injury Physics
      • Defining and Diagnosing bTBI
      • Experimental Animal Models of bTBI
      • Neurological Effects
      • Injury and Recovery Mechanisms
      • Body Fluid–Based Biomarkers of Injury
      • Concluding Remarks and Future Directions
      • References
    • Chapter 14. Thallium
      • Introduction
      • Background
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 15. Arsenicals: Toxicity, Their Use as Chemical Warfare Agents, and Possible Remedial Measures
      • Introduction
      • Background
      • Arsine
      • Organic Arsenicals
      • Inorganic Arsenic
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 16. Fluoroacetate
      • Introduction
      • Background
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity and Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 17. Strychnine
      • Introduction
      • Background
      • Pharmacokinetics and Toxicokinetics
      • Clinical Symptomatology
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 18. Superwarfarins
      • Introduction
      • Background
      • Classification of Superwarfarins
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity
      • General Treatment Recommendations
      • Concluding Remarks and Future Directions
      • References
    • Chapter 19. PCBs, Dioxins and Furans: Human Exposure and Health Effects
      • Introduction
      • Historical Background
      • Human Exposure to PCBs, PCDDs, and PCDFs
      • Physico-Chemical Properties and Global Distribution
      • Analytical Methods
      • Mechanism of Action and Toxicity
      • Concluding Remarks and Future Directions
      • References
    • Chapter 20. Polycyclic Aromatic Hydrocarbons: Implications for Developmental, Molecular, and Behavioral Neurotoxicity
      • Introduction
      • Background
      • PAH Experimental Model Systems
      • Implications
      • Concluding Remarks and Future Directions
      • References
    • Chapter 21. Carbon Monoxide: From Public Health Risk to Painless Killer
      • Introduction
      • Historical Background
      • Epidemiological Considerations
      • Toxicokinetics and Toxicodynamics
      • Mechanism of Toxicity
      • Toxicity of Carbon Monoxide
      • Physiological Roles of Carbon Monoxide
      • Treatment of Carbon Monoxide Overdose
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 22. Methyl Isocyanate: The Bhopal Gas
      • Introduction
      • The Making of a Disaster
      • Toxicokinetics of Isocyanates
      • Mechanism of Death Following Exposure to MIC
      • The Cyanide Controversy
      • Toxicity of Isocyanates
      • Treatment
      • Toxic Potential of MIC Beyond the Bhopal Disaster
      • Benzyl Chlorines and Other Chemicals at Bhopal
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 23. Cyanide Toxicity and its Treatment
      • Introduction
      • Sources of Exposure
      • Toxic Levels of Cyanide
      • Detection and Estimation of Cyanide
      • Toxicokinetics of Cyanide
      • Mechanism of Action
      • Diagnosis and Clinical Features of Cyanide Poisoning
      • Treatment of Cyanide Poisoning
      • Concluding Remarks and Future Directions
      • Acknowledgment
      • References
    • Chapter 24. Chlorine
      • Introduction
      • History of Use
      • Absorption, Distribution, Metabolism, and Excretion
      • Mechanism of Toxicity
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 25. Phosgene
      • Introduction
      • Background
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 26. Other Toxic Chemicals as Potential Chemical Warfare Agents
      • Introduction
      • General
      • Specific Agents
      • Nonlethal Weapons
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 27. Ricin
      • Introduction
      • History of Biological Weapons
      • The Weaponization of Biological Agents
      • The Family of Ribosome-Inactivating Proteins
      • The Ricin Toxin Structure and Biosynthesis
      • The Cellular Internalization of Ricin
      • N-glycosidase Activity of Ricin
      • Signs and Symptoms of Ricin Exposure
      • Field-Forward Biological Agent Detection
      • Concluding Remarks and Future Directions
      • References
    • Chapter 28. Botulinum Toxin
      • Introduction
      • Background
      • Epidemiology
      • Pathogenesis
      • Toxicokinetics
      • Mechanism of Action
      • Toxicity
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 29. Anthrax
      • Introduction
      • History
      • Epidemiology
      • Pathogenesis
      • Toxicokinetics
      • Mechanism of Toxicity
      • Toxicity
      • Detection and Diagnosis
      • Risk Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 30. Onchidal and Fasciculins
      • Introduction
      • Background
      • Mechanism of Action and Biological Effects
      • Experimental and Human Toxicity
      • Computational Toxicology Assessment
      • Treatment
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • Disclosures
      • References
    • Chapter 31. Cyanobacterial (Blue-Green Algae) Toxins
      • Introduction
      • Hepatotoxins
      • Neurotoxins
      • Concluding Remarks and Future Directions
      • References
    • Chapter 32. Radiation and Health Effects
      • Introduction
      • Historical Perspective
      • Basic Radiation Concepts
      • Interaction of Radiation with Matter
      • Absorbed Dose
      • Consequences of Radiation-Induced DNA Damage
      • Human Exposures and Radiation Toxicity
      • Human Population and Health Risks
      • Radiation Hormesis
      • Biomonitoring and Biomarkers of radiation
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 33. Depleted Uranium
      • Introduction
      • Background
      • Exposure Pathways and Body Retention of DU
      • Pharmacokinetics
      • Mechanism of Action
      • Toxicity of DU Exposure
      • Treatment
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
  • Section III: Target Organ Toxicity
    • Chapter 34. Chemical Warfare Agents and the Nervous System
      • Introduction
      • Overview of the Nervous System
      • Types of Neurotoxicity
      • Selected CWAs That Affect the Nervous System
      • Concluding Remarks and Future Directions
      • References
    • Chapter 35. Behavioral Toxicity of Nerve Agents
      • Introduction
      • Methods Used to Evaluate Behavioral Effects of Nerve Agents
      • Long-Term Behavioral Effects of Acute High-Level Exposure to Nerve Agents
      • Chronic Behavioral Effects of Single or Repeated Low-Level Exposure to Nerve Agents
      • Concluding Remarks and Future Direction
      • References
    • Chapter 36. The Respiratory Toxicity of Chemical Warfare Agents
      • Introduction
      • History of CWA Use
      • The Respiratory System
      • Pulmonary Agents
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 37. Cardiovascular System as a Target of Chemical Warfare Agents
      • Introduction
      • Background
      • Signatures of Cardiac Toxicity
      • Indices of the Toxicity of Warfare Agents
      • Specific Warfare Agents of Concern Regarding the Heart
      • Other Terror Agents
      • Therapeutics Undergoing Development
      • Concluding Remarks and Future Directions
      • References
    • Chapter 38. Ocular Toxicity of Chemical Warfare Agents
      • Introduction
      • Background
      • Vesicants
      • Nerve Agents
      • Psychomimetic Incapacitating Agents
      • Blood Agents
      • Choking Agents
      • Riot Control Agents
      • Biological Toxins
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 39. Dermal Toxicity of Sulfur Mustard
      • Introduction
      • Background
      • Pathogenesis
      • Models of Dermal SM Exposure
      • Therapeutics
      • Concluding Remarks and Future Directions
      • References
    • Chapter 40. Skeletal Muscle
      • Introduction
      • Behavioral Effects
      • Cholinergic System
      • Noncholinergic System
      • Muscle Activity—EMG
      • Muscle Fiber Histopathology
      • Muscle Cytotoxicity Biomarkers
      • Skeletal Muscle and Tolerance Development
      • Skeletal Muscle Involvement in IMS
      • Prevention/Treatment of Myopathy
      • AChE Reactivators and ACh Receptor Blockers
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 41. Reproductive Toxicity and Endocrine Disruption of Potential Chemical Warfare Agents
      • Introduction
      • Important Definitions and Concepts
      • The Reproductive Toxicity of Selected Toxicants
      • Concluding Remarks and Future Directions
      • References
    • Chapter 42. Liver Toxicity of Chemical Warfare Agents
      • Introduction
      • Structural Organization of the Liver
      • Factors Influencing Hepatic Toxicity
      • Warfare Agents Affecting Liver
      • Concluding Remarks and Future Directions
      • References
    • Chapter 43. Renal System
      • Introduction
      • Anatomy and Physiology
      • Toxic Responses of the Urinary System
      • Toxic Effects of Chemical Warfare Agents
      • Concluding Remarks and Future Directions
      • References
    • Chapter 44. The Immune System as a Target for Chemical Warfare Agents
      • Introduction
      • The Immune System
      • Targets of Immunotoxicity
      • Exposition of Autoantigens and Interference with Co-Stimulatory Signals
      • Regulation of the Immune Response
      • Immunotoxicity of CWAs
      • Concluding Remarks and Future Directions
      • References
    • Chapter 45. Alternative Animal Toxicity Testing of Chemical Warfare Agents
      • Introduction
      • Brief History of Chemical Warfare Use
      • Top Five Chemical Warfare Agents
      • The Concept of 3Rs
      • International Cooperation on Alternative Test Methods
      • Alternatives to Animal Testing of Chemical Warfare Agents
      • Animal Efficacy Rule
      • Human on a Chip
      • Concluding Remarks and Future Directions
      • References
  • Section IV: Special Topics
    • Chapter 46. Genomics and Proteomics in Brain Complexity in Relation to Chemically Induced PTSD
      • Introduction
      • The Effect of PTSD on Different Regions of the Brain
      • The Hypothalamic-Pituitary-Adrenal Axis
      • Hippocampus
      • Amygdala
      • Cortex
      • Understanding PTSD: Genomics and Proteomics
      • Applications of Genomic and Transcriptomics Methods
      • The Role of ncRNA and Epigenetics in PTSD
      • Toxic Chemical Exposure and Human Diseases
      • Genomic Applications: Understanding the Relationship Between PTSD and Chemical Toxicity
      • Proteomics
      • Neuroproteomics: Proteomics Applications in Neuroscience
      • Proteomics Approaches to Understanding Natural and Chemical Toxicity-Induced PTSD
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 47. Clinical and Cellular Aspects of Traumatic Brain Injury
      • Introduction
      • A Variety of Mouse Models Are Used to Study TBI
      • Clinical Manifestation and Management of TBI
      • TBIs Increase ICP
      • Cognitive Impairments After TBI Result from Neuronal and Synaptic Loss
      • Primary and Secondary Injuries Initiate Cell Death Through Distinct Pathways
      • Potential Mechanisms of Subtle Synaptic Impairments in TBI
      • TBIs Reproduce Pathological Hallmarks of Alzheimer Disease
      • Concluding Remarks and Future Directions
      • References
    • Chapter 48. Excitotoxicity, Oxidative Stress, and Neuronal Injury
      • Introduction
      • Excitotoxicity and Oxidative Injury
      • Lipid Peroxidation and In Vivo Markers of Oxidative Damage
      • Anti-AChE-Induced Seizures, Oxidative Injury, and Neurodegeneration
      • Oxidative Damage and Dendritic Degeneration Following KA-Induced Excitotoxicity
      • Neuroinflammation and Oxidative Injury
      • Suppression of Seizure-Induced Oxidative Injury and Neurodegeneration
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 49. Blood–Brain Barrier Damage and Dysfunction by Chemical Toxicity
      • Introduction
      • Structure and Function of the BBB
      • In vivo and in vitro Models to Study the BBB
      • Gender Differences in the BBB
      • The BBB in Young and Adult Brains
      • Transport of Molecules Across the BBB
      • Effects of Toxic Agents on the BBB
      • Bacterial Toxin-Induced BBB Damage
      • GWI and the BBB
      • Effects of Blasts on the BBB
      • Excitotoxicity, Stress and the BBB
      • Brain Barriers and CNS Diseases
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 50. Neuropathologic Effects of Chemical Warfare Agents
      • Introduction
      • Background
      • Acute Effects of Symptomatic Exposure
      • Prolonged Effects of Symptomatic Exposure
      • Organophosphate-Induced Delayed Neuropathy
      • OP-Associated Muscle Weakness
      • Effects of Subsymptomatic Exposure to Nerve Agents
      • Concluding Remarks and Future Directions
      • References
    • Chapter 51. The Effects of Organophosphates in the Early Stages of Human Muscle Regeneration
      • Introduction
      • Regeneration Process in Human Skeletal Muscle
      • Noncholinergic Effects of DFP in Regenerating Human Skeletal Muscle
      • Expression and Role of AChE in Human Myoblasts
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 52. Cholinesterase Inhibitors: From Molecular Mechanisms of Action to Current and Future Prospects
      • Introduction
      • Human Cholinesterases
      • Anti-ChEs and the Cholinergic System
      • Detection and Prevention of Anti-ChE Toxicity
      • Concluding Remarks
      • Acknowledgments
      • References
  • Section V: Risks to Animals and Wildlife
    • Chapter 53. Potential Agents That Can Cause Contamination of Animal Feedstuffs and Terror
      • Introduction
      • Mycotoxins and Toxigenic Fungi
      • Microbial Toxins
      • Plant Toxins
      • Rapidly Acting and Easily Available Substances
      • Persistent Organic Compounds
      • Heavy Metals and Metalloids
      • Contaminated Transport Vessels
      • Concluding Remarks and Future Directions
      • References
    • Chapter 54. Chemical Warfare Agents and Risks to Animal Health
      • Introduction
      • CWAs
      • Concluding Remarks and Future Directions
      • References
    • Chapter 55. Threats to Wildlife by Chemical and Warfare Agents
      • Introduction
      • Background
      • Illicit and Restricted Substances
      • Cyanide
      • Ricin (Castor Bean)
      • Pesticides
      • Concluding Remarks and Future Directions
      • References
  • Section VI: Toxicokinetics, Toxicodynamics and Physiologically-Based Pharmacokinetics
    • Chapter 56. Toxicokinetic Aspects of Nerve Agents and Vesicants
      • Introduction
      • Overview of Invasion Processes of CWAs
      • Nerve Agents
      • Vesicants
      • Concluding Remarks and Future Directions
      • References
    • Chapter 57. Toxicokinetics and Toxicodynamics of DFP
      • Introduction
      • Physico-Chemical Properties and Chemical Identification of DFP
      • History of DFP Synthesis and its Relationship with Development of Warfare Nerve Agents
      • Toxicokinetic and Biotransformation of DFP and Studies on DFPase
      • Acute Toxicity of DFP and Interaction with AChE
      • DFP in Studies on Neurotoxicity and Therapy with Reactivators
      • Interaction of DFP with Other Esterases
      • Concluding Remarks and Future Directions
      • References
    • Chapter 58. Physiologically Based Pharmacokinetic Modeling of Chemical Warfare Agents
      • Introduction
      • Development of PBPK Models
      • Need for Improved Measures of CWNA Exposure—The Use of PBPK Analysis of Data
      • Relationship Between Regenerated Sarin and AChE Activity and Its Use as a Dose Surrogate
      • General PBPK Model Structure
      • PBPK Simulation of Cholinesterase Inhibition and Regenerated GB
      • Concluding Remarks and Future Directions
      • References
    • Chapter 59. Biotransformation of Warfare Nerve Agents
      • Introduction
      • Chemical Aspects of Biotransformation of WNAs
      • Esterases Involved in Metabolism of WNAs
      • Protein Binding
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
  • Section VII: Analytical Methods, Biosensors and Biomarkers
    • Chapter 60. On-Site Detection of Chemical Warfare Agents
      • Introduction
      • Properties of CWAs
      • Concept of On-Site Detection
      • The Currrent Situation of Detection Technology
      • Comparison of Existing On-Site Detection Technologies
      • Development of New On-Site Detection Technologies
      • Concluding Remarks and Future Directions
      • References
    • Chapter 61. Laboratory Analysis of Chemical Warfare Agents, Adducts, and Metabolites in Biomedical Samples
      • Introduction
      • Nerve Agents
      • Sulfur Mustard and Lewisite
      • Concluding Remarks and Future Directions
      • References
    • Chapter 62. Biosensors for the Detection of OP Nerve Agents
      • Introduction
      • Biosensors
      • Electrochemical Biosensors for Detecting OP Compounds
      • Miscellaneous Biosensors for OP Detection
      • Concluding Remarks and Future Directions
      • References
    • Chapter 63. Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents
      • Introduction
      • OP Compounds
      • OPIDN
      • NTE
      • Kinetics of OP Inhibitor–Serine Hydrolase Interactions
      • Biomarkers
      • Biosensors
      • Concluding Remarks and Future Directions
      • References
    • Chapter 64. Biomarkers of Exposure to Organophosphorus Poisons: A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine
      • Introduction
      • Use of AChE and BChE Biomarkers in the Clinic
      • Methods to Detect OP Adducts on AChE and BChE
      • Why Are New Biomarkers Needed?
      • New Biomarkers
      • Covalent Binding of OP to Tyrosine
      • Motif for OP Binding to Tyrosine
      • Characteristics of OP Binding to Tyrosine
      • Methods for Detecting OP Binding to Tyrosine
      • OPs Make a Covalent Bond with Serine, Threonine, Tyrosine, Lysine, and Histidine
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 65. Monitoring of Blood Cholinesterase Activity in Workers Exposed to Nerve Agents
      • Introduction
      • Determination of ChEs
      • Factors Influencing Activity of ChEs
      • Diagnosis of OP Poisoning
      • Monitoring of Blood ChE Activity in Workers with Nerve Agents
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
  • Section VIII: Prophylactic, Therapeutic and Countermeasures
    • Chapter 66. Pharmacological Prophylaxis Against Nerve Agent Poisoning: Experimental Studies and Practical Implications
      • Introduction
      • Protection of AChE Against Inhibition
      • Scavengers
      • Prophylaxis with Current Antidotes
      • Prophylactic Use of Other Drugs
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 67. Prophylactic and Therapeutic Measures in Nerve Agents Poisoning
      • Introduction
      • Background
      • Mechanism of Action
      • Prophylactic Measures
      • Therapeutic Measures
      • Concluding Remarks and Future Directions
      • References
    • Chapter 68. Medical Management of Chemical Toxicity in Pediatrics
      • Introduction
      • Background
      • History of Pediatric Chemical Casualties
      • Challenges to Managing Pediatric Chemical Casualties
      • Effects of Specific Agents
      • Decontamination of Children
      • Preparation for a Chemical Event
      • Concluding Remarks and Future Directions
      • References
    • Chapter 69. Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling of Countermeasures to Nerve Agents
      • Introduction
      • Background
      • Current Countermeasures
      • Novel Countermeasures
      • PBPK/PD Modeling
      • Development of PBPK/PD Models
      • Experimental and QSAR Methodologies to Predict Blood and Tissue Partition Coefficients
      • Interaction PBPK/PD Model for NAs and Countermeasures
      • Health Effects Assessment and Countermeasure Optimization
      • Concluding Remarks and Future Directions
      • References
    • Chapter 70. Strategies to Enhance Medical Countermeasures After the Use of Chemical Warfare Agents on Civilians
      • Introduction
      • Overall Strategic Approach
      • CounterACT Program Structure
      • Scope of Research
      • The Civilian Versus Military Threat Spectrum
      • Basic/mechanistic Research and Target Identification
      • In Vitro and In Vivo Models for Efficacy Screening
      • Advanced Preclinical Development and Clinical Studies
      • Pretreatments
      • Post-exposure (Pretarget) Prophylactic Therapies
      • Post-exposure Posttarget Treatment
      • Concluding Remarks and Future Directions
      • References
    • Chapter 71. Pyridinium Oximes in the Treatment of Poisoning with Organophosphorus Compounds
      • Introduction
      • Interaction of Cholinesterases with OP Inhibitors
      • Clinical Aspects of Acute OP Poisoning
      • Antidotes in the Treatment of OP Poisoning
      • Pyridinium Oximes in Management of Poisoning with Warfare Nerve Agents
      • Pyridinium Oximes in Management of Poisoning with OP Pesticides
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 72. Novel Cholinesterase Reactivators
      • Introduction
      • OP AChE Inhibitors
      • Acetylcholinesterase (AChE; EC 3.1.1.7)
      • Antidotes for AChE Inhibited by OP Compounds
      • Design and Synthesis of New AChE Reactivators
      • In Vitro Evaluation of Selected AChE Reactivators
      • The Structure–Activity Relationship of AChE Reactivators
      • Promising Oximes
      • Recent Trends in Development of New AChE Reactivators
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 73. Paraoxonase (PON1) and Detoxication of Nerve Agents
      • Introduction
      • PON1 Polymorphisms: Defining PON1 Status
      • PON1 and the Toxicity of OP Insecticides
      • PON1 and the Toxicity of Nerve Agents
      • PON1 as a Therapeutic Agent
      • Concluding Remarks and Future Directions
      • Acknowledgments
      • References
    • Chapter 74. The Role of Carboxylesterases in Therapeutic Intervention of Nerve Gases Poisoning
      • Introduction
      • Enzymology
      • Origin of Plasma CarbE
      • Role of Plasma CarbE
      • Concluding Remarks and Future Directions
      • References
    • Chapter 75. Catalytic Bioscavengers: The New Generation of Bioscavenger-Based Medical Countermeasures
      • Introduction
      • Stoichiometric Scavengers
      • Pseudocatalytic Bioscavengers
      • Catalytic Scavengers
      • Requirements
      • Potential Enzymes
      • Concluding Remarks and Future Directions
      • References
  • Section IX: Decontamination and Detoxification
    • Chapter 76. Rapid Decontamination of Chemical Warfare Agents from the Skin
      • Background: The Nature of Human Skin
      • Background: Nerve Agents
      • Background: Vesicating Agents (Distilled Sulfur Mustard, HD; Impure Sulfur Mustard, H; Lewisite, L)
      • Model Systems to Measure Absorption, Removal, and Decontamination
      • Decontamination Requirements
      • Decontamination Schemes
      • Concluding Remarks and Future Directions
      • References
  • Index

Details

No. of pages:
1198
Language:
English
Copyright:
© Academic Press 2015
Published:
Imprint:
Academic Press
eBook ISBN:
9780128004944
Hardcover ISBN:
9780128001592

About the Editor

Ramesh C. Gupta

Ramesh C. Gupta

Dr. Ramesh C. Gupta, Professor & Head of Toxicology Department at Murray State university, is engaged in experimental brain research in relation to Alzheimer(s) disease (AD) and pesticide toxicity. He has delivered lectures in Australia, Italy, Japan, Germany, France, Switzerland, Spain, Czech Republic, China, South Korea, and Sweden. He served the panels of NIH, CDC, NIOSH, and NAS. He has >350 publications to his credit, including six major books: (1) Toxicology of Organophosphate and Carbamate Compounds, (2) Veterinary Toxicology: Basic and Clinical Principles, (3) Handbook of Toxicology of Chemical Warfare Agents, (4) Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology, (5) Reproductive and Developmental Toxicology, and (6) Biomarkers in Toxicology. He is recipient of Murray State University's distinguished researcher award of the year-2006. He is a diplomate of American Board of Toxicology, and fellow of American College of Toxicology, American College of Nutrition, and Academy of Toxicological Sciences.

Affiliations and Expertise

Professor and Head, Toxicology Department, Breathitt Veterinary Center, Murray State University, Hopkinsville, KY, USA

Reviews

"...a large, high-quality publication...provides a broader perspective than the few other titles in this field. This edition expands topics and updates references, driven by the ongoing threat, use, and research of chemical warfare agents around the world. Score: 92 - 4 Stars" --Doody's