Handbook of Toxicology of Chemical Warfare Agents

Front Cover

Handbook of Toxicology of Chemical warfare agents

Copyright Page

Dedication

Contents

List of Contributors

Foreword

SECTION I Introduction, Historical Perspective, and Epidemiology

CHAPTER 1 - Introduction

CHAPTER 2 - Historical Perspective of Chemical Warfare Agents

I. INTRODUCTION

II. THE FIRST SUSTAINED USE OFCHEMICALS AS AGENTS OF WARFARE

III. INITIAL COUNTERMEASURES

IV. EVENTS AFTER WORLD WAR I

V. WORLD WAR II

VI. POST-WORLD WAR II

VII. INCAPACITANTS AND TOXINS

VIII. RECENT EXPERIENCES

IX. TERRORIST USE

X. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 3 - Global Impact of Chemical Warfare Agents Used Before and After 1945

I. INTRODUCTION

II. BACKGROUND

III. MILITARY USE OF CWs

IV. THE PERIOD BETWEEN WWIAND WWII

V. WWII

VI. THE PERIOD AFTER WWIIAND THE COLD WAR

VII. UNINTENTIONAL USE OF TOXICCHEMICALS

VIII. TERRORIST USE OF CW

IX. NEGOTIATIONS

X. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 4 - The Tokyo Subway Sarin Attack: Toxicological Whole Truth

I. INTRODUCTION

II. SARIN TOXICITY AND MECHANISMOF ONSET

III. OVERVIEW OF THE TOKYO SUBWAYSARIN ATTACK

IV. EMERGENCY TREATMENTOF SARIN TOXICITY

V. ACUTE AND CHRONIC SYMPTOMSOF SARIN TOXICITY

VI. LABORATORY FINDINGS IN SARINTOXICITY

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 5 - Epidemiology of Chemical Warfare Agents

I. INTRODUCTION

II. PRE-WORLD WAR II

III. WORLD WAR II

IV. POST-WORLD WAR II

V. IRAN–IRAQ WAR

VI. GULF WAR 1991

VII. TERRORISM

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

SECTION II Agents that can be Used as Weapons of Mass Destruction

CHAPTER 6 Organophosphate Nerve Agents

I. INTRODUCTION

II. BACKGROUND

III. MECHANISM OF ACTION

IV. TOXICITY

V. RISK ASSESSMENT

VI. TREATMENT

VII. CONCLUDING REMARKS ANDFUTURE DIRECTION

Acknowledgments

References

CHAPTER 7 Russian VX

I. INTRODUCTION

II. BACKGROUND

III. MECHANISMS OF ACTIONAND TOXICITY

IV. TOXICOMETRY AND HYGIENICREGULATIONS

V. PRINCIPLES OF THERAPY

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 8 Mustards and Vesicants

I. INTRODUCTION

II. HISTORY AND BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 9 Arsenicals: Toxicity, their Use as Chemical Warfare Agents, and Possible Remedial Measures

I. INTRODUCTION

II. BACKGROUND

III. ARSINE

IV. ORGANIC ARSENICALS

V. INORGANIC ARSENIC

VI. TREATMENT

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 10 Psychotomimetic Agent BZ (3-Quinuclidinyl Benzilate)

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS AND MECHANISMOF ACTION

IV. TOXICITY

V. RISK ASSESSMENT

VI. TREATMENT

VII. ANALYTICAL METHODS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 11 Onchidal and Fasciculins

I. INTRODUCTION

II. BACKGROUND

III. MECHANISM OF ACTIONAND BIOLOGICAL EFFECTS

IV. EXPERIMENTAL AND HUMANTOXICITY

V. RISK ASSESSMENT

VI. TREATMENT

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 12 Riot Control Agents

I. INTRODUCTION

II. HISTORY

III. BACKGROUND

IV. MECHANISM OF ACTION

V. TOXICOKINETICS

VI. TOXICITY

VII. RISK ASSESSMENT

VIII. TREATMENT

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 13 Fluoroacetate

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY AND RISK ASSESSMENT

VI. TREATMENT

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 14 Strychnine

I. INTRODUCTION

II. BACKGROUND

III. PHARMACOKINETICSAND TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 15 Superwarfarins

I. INTRODUCTION

II. BACKGROUND

III. CLASSIFICATIONOF SUPERWARFARINS

IV. TOXICOKINETICS

V. MECHANISM OF ACTION

VI. TOXICITY

VII. GENERAL TREATMENTRECOMMENDATIONS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 16 Thallium

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 17 Polycyclic Aromatic Hydrocarbons: Exposure from Emission Products and from Terrorist Attacks on US Targets - Implications for Developmental Central Nervous System Toxicity

I. INTRODUCTION

II. BACKGROUND

III. PAH-INDUCED PHYSIOLOGICAL ANDBEHAVIORAL TOXIC MANIFESTATIONSIN ANIMAL MODELS: EARLY PAHSTUDIES WHICH IMPLICATED THE CNSAS A TARGET

IV. UNDERLYING MECHANISMS OF PAHNEUROTOXICITY

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 18 PCBs, Dioxins, and Furans: Human Exposure and Health Effects

I. INTRODUCTION

II. BACKGROUND

III. HUMAN EXPOSURE TO PCBS, PCDDS,AND PCDFS

IV. PHYSICOCHEMICAL PROPERTIESAND GLOBAL DISTRIBUTION

V. ANALYTICAL METHODS

VI. MECHANISM OF ACTIONAND TOXICITY

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 19 Cyanide Toxicity and its Treatment

I. INTRODUCTION

II. SOURCES OF EXPOSURE

III. TOXIC LEVELS OF CYANIDE

IV. DETECTION AND ESTIMATIONOF CYANIDE

V. TOXICOKINETICS OF CYANIDE

VI. MECHANISM OF ACTION

VII. DIAGNOSIS AND CLINICALFEATURES OF CYANIDE POISONING

VIII. TREATMENT OF CYANIDEPOISONING

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 20 Carbon Monoxide: From Public Health Risk to Painless Killer

I. INTRODUCTION

II. HISTORICAL BACKGROUND

III. EPIDEMIOLOGICALCONSIDERATIONS

IV. TOXICOKINETICS ANDTOXICODYNAMICS

V. MECHANISM OF TOXICITY

VI. TOXICITY OF CARBON MONOXIDE

VII. PHYSIOLOGICAL ROLESOF CARBON MONOXIDE

VIII. TREATMENT OF CARBONMONOXIDE OVERDOSE

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 21 Methyl Isocyanate: The Bhopal Gas

I. INTRODUCTION

II. BACKGROUND

III. THE MAKING OF A DISASTER

IV. TOXICOKINETICS OF ISOCYANATES

V. MECHANISM OF ACTION

VI. THE CYANIDE CONTROVERSY: MICOR HCN?

VII. TOXICITY OF ISOCYANATES

VIII. TREATMENT

IX. TOXIC POTENTIAL OF MIC BEYONDTHE BHOPAL DISASTER

X. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 22 Chlorine

I. INTRODUCTION

II. HISTORICAL BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF TOXICITY

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 23 Phosgene

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 24 Other Toxic Chemicals as Potential Chemical Warfare Agents

I. INTRODUCTION

II. GENERAL

III. SPECIFIC AGENTS

IV. NONLETHAL WEAPONS

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 25 Ricin and Abrin

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 26 Trichothecene Mycotoxins

I. INTRODUCTION

II. BACKGROUND

III. TOXICOKINETICS

IV. MECHANISM OF ACTION

V. TOXICITY

VI. RISK ASSESSMENT

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 27 Toxins of Cyanobacteria

I. INTRODUCTION

II. BACKGROUND

III. STRUCTURE, MECHANISMOF ACTION, AND TOXICITYOF CYANOTOXINS

B. Neurotoxins

IV. RISK ASSESSMENT

V. TREATMENT

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 28 Radiation and Health Effects

I. INTRODUCTION

II. BASIC RADIATION CONCEPTS

III. INTERACTION OF RADIATIONWITH MATTER

IV. ABSORBED DOSE

V. MECHANISMS OF DNA DAMAGEAND MUTAGENESIS

VI. ANIMAL EXPOSURESAND RADIATION TOXICITY

VII. HUMAN EXPOSURESAND RADIATION TOXICITY

VIII. RADIATION HORMESIS

IX. CONSEQUENCES OF RADIATIONTHERAPY

X. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 29 Depleted Uranium

I. INTRODUCTION

II. BACKGROUND

III. EXPOSURE PATHWAYS AND BODYRETENTION OF DU

IV. PHARMACOKINETICS

V. MECHANISM OF ACTION

VI. TOXICITY OF DEPLETED URANIUMEXPOSURE

VII. TREATMENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 30 Botulinum Toxin

I. INTRODUCTION

II. BACKGROUND

III. EPIDEMIOLOGY

IV. PATHOGENESIS

V. TOXICOKINETICS

VI. MECHANISM OF ACTION

VII. TOXICITY

VIII. RISK ASSESSMENT

IX. TREATMENT

X. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 31 Anthrax

I. INTRODUCTION

II. HISTORY

III. EPIDEMIOLOGY

IV. PATHOGENESIS

V. TOXICOKINETICS

VI. MECHANISM OF TOXICITY

VII. TOXICITY

VIII. DETECTION AND DIAGNOSIS

IX. RISK ASSESSMENT

X. TREATMENT

XI. CONCLUDING REMARKSAND FUTURE DIRECTION

References

SECTION III Target Organ Toxicity

CHAPTER 32 The Nervous System as a Target for Chemical Warfare Agents

I. INTRODUCTION

II. OVERVIEW OF THE NERVOUSSYSTEM

III. SPECIAL FEATURESOF THE NERVOUS SYSTEM

IV. TYPES OF NEUROTOXICANTS

V. CELLULAR MAINTENANCE

VI. VOLTAGE-GATED ION CHANNELS

VII. NEUROTRANSMITTER SYSTEMS

VIII. SELECTED CWAS THAT AFFECTNERVOUS SYSTEM FUNCTION

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 33 Behavioral Toxicity of Nerve Agents

I. INTRODUCTION

II. THE METHODS USED TO EVALUATEBEHAVIORAL EFFECTS OF NERVEAGENTS

III. LONG-TERM BEHAVIORAL EFFECTSOF ACUTE HIGH-LEVEL EXPOSURE TONERVE AGENTS

IV. CHRONIC BEHAVIORAL EFFECTSOF SINGLE OR REPEATED LOW-LEVELEXPOSURE TO NERVE AGENTS

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 34 Cardiovascular System as a Target of Chemical Warfare Agents

I. INTRODUCTION

II. BACKGROUND

III. SIGNATURES OF CARDIACTOXICITY

IV. INDICES OF THE TOXICITYOF WARFARE AGENTS

V. SPECIFIC WARFARE AGENTS OFCONCERN REGARDING THE HEART

VI. OTHER TERROR AGENTS

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 35 Skeletal Muscle

I. INTRODUCTION

II. BEHAVIORAL EFFECTS

III. CHOLINERGIC SYSTEM

IV. NONCHOLINERGIC SYSTEM

V. MUSCLE ACTIVITY – EMG

VI. MUSCLE FIBER HISTOPATHOLOGY

VII. MUSCLE CYTOTOXICITYBIOMARKERS

VIII. SKELETAL MUSCLESAND TOLERANCE DEVELOPMENT

IX. SKELETAL MUSCLE INVOLVEMENTIN INTERMEDIATE SYNDROME

X. PREVENTION/TREATMENTOF MYOPATHY

XI. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 36 Reproductive Toxicity and Endocrine Disruption of Potential Chemical Warfare Agents

I. INTRODUCTION

II. IMPORTANT DEFINITIONSAND CONCEPTS

III. THE REPRODUCTIVE TOXICITYOF SELECTED TOXICANTS

IV. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 37 Liver Toxicity of Chemical Warfare Agents

I. INTRODUCTION

II. STRUCTURAL ORGANIZATIONOF THE LIVER

III. FACTORS INFLUENCING HEPATICTOXICITY

IV. WARFARE AGENTS AFFECTINGLIVER

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 38 Renal Toxicity

I. INTRODUCTION

II. RENAL ANATOMY AND PHYSIOLOGY

III. TOXIC EFFECTS ON THE KIDNEY

IV. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 39 Ocular Toxicity of Sulfur Mustard

I. INTRODUCTION

II. BACKGROUND

III. OCULAR TOXICITYAND TOXICOKINETICS

IV. MECHANISM OF ACTION

V. RISK ASSESSMENT

VI. TREATMENTS

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 40 Immunotoxicity

I. INTRODUCTION

II. THE IMMUNE SYSTEM

III. TARGETS OF IMMUNOTOXICITY

IV. EXPOSITION OF AUTOANTIGENSAND INTERFERENCE WITHCO-STIMULATORY SIGNALS

V. INDUCTION OF INFLAMMATIONAND NONCOGNATE T–B COOPERATION

VI. REGULATION OF THE IMMUNERESPONSE

VII. IMMUNOTOXICITY OF CHEMICALWARFARE AGENTS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 41 Dermal Toxicity of Sulfur Mustard

I. INTRODUCTION

II. BACKGROUND

III. PATHOGENESIS

IV. MODELS OF DERMAL SULFURMUSTARD EXPOSURE

V. THERAPEUTICS

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

References

SECTION IV Special Topics

CHAPTER 42 Excitotoxicity, Oxidative Stress, and NeuronalnbspInjury

I. INTRODUCTION

II. EXCITOTOXICITY ANDNEURODEGENERATION

III. OXIDATIVE INJURY

IV. LIPID PEROXIDATION AND IN VIVOMARKERS OF OXIDATIVE DAMAGE

V. HIGH-ENERGY PHOSPHATES

VI. NITRIC OXIDE (NO/NOS)

VII. DENDRITIC INJURY

VIII. ANTICHOLINESTERASE-INDUCEDSEIZURES, OXIDATIVE INJURY,AND NEURODEGENERATION

IX. OXIDATIVE DAMAGEAND DENDRITIC DEGENERATIONFOLLOWING KAINIC ACID-INDUCEDEXCITOTOXICITY

X. SUPPRESSION OF SEIZURE-INDUCEDOXIDATIVE INJURY ANDNEURODEGENERATION

XI. NMDA RECEPTOR ANTAGONIST(MEMANTINE)

XII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 43 Neuropathologic Effects of Chemical Warfare Agents

I. INTRODUCTION

II. BACKGROUND

III. ACUTE EFFECTS OF SYMPTOMATICEXPOSURE

IV. PROLONGED EFFECTSOF SYMPTOMATIC EXPOSURE

V. ORGANOPHOSPHATE-INDUCEDDELAYED NEUROTOXICITY (OPIDN)

VI. ORGANOPHOSPHATE-ASSOCIATEDMUSCLE WEAKNESS

VII. EFFECTS OF SUBSYMPTOMATICEXPOSURE TO NERVE AGENTS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 44 Molecular and Transcriptional Responses to Sarin Exposure

I. INTRODUCTION

II. BACKGROUND

III. SARIN-INDUCED CLINICALCHANGES AS A FUNCTION OFCELLULAR AND MOLECULARALTERATIONS

IV. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 45 The Effects of Organophosphates in the Early Stages of Human Muscle Regeneration

I. INTRODUCTION

II. REGENERATION PROCESS IN THEHUMAN SKELETAL MUSCLE

III. THE EFFECTS OF DFP ON THEREGENERATION PROCESS IN THEHUMAN SKELETAL MUSCLE

IV. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 46 Organophosphate Intoxication: Molecular Consequences, Mechanisms and Solutions

I. INTRODUCTION

II. HUMAN CHOLINESTERASES:THE COMMON CORE

III. HUMAN CHOLINESTERASES:MYRIAD OF MOLECULAR FORMS

IV. REGULATION OF AChE GENEEXPRESSION

V. LOCATION AND FUNCTION OF AChEIN THE NEUROMUSCULAR JUNCTION

VI. BUTYRYLCHOLINESTERASE AS THEINHERENT PROTECTOR OF AChE

VII. ACUTE TOXICITY PRODUCESSHORT-TERM LOSS OF FUNCTION

VIII. LONG-TERM EFFECTS OF AChE-ROVERPRODUCTION

IX. PREVENTION OFANTICHOLINESTERASE TOXICITY:THE ‘‘NEXT GENERATION’’

X. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

SECTION V Risks to Animals and Wildlife

CHAPTER 47 Chemical Warfare Agents and Risks to Animal Health

I. INTRODUCTION

II. CHEMICAL WARFARE AGENTS

III. CONCLUDING REMARKS ANDFUTURE DIRECTION

References

CHAPTER 48 Potential Agents that Can Cause Contamination of Animal Feedstuffs and Terror

I. INTRODUCTION

II. MYCOTOXINS AND TOXIGENICFUNGI

III. MICROBIAL TOXINS

IV. PLANT TOXINS

V. RAPIDLY ACTING AND EASILYAVAILABLE SUBSTANCES

VI. PERSISTENT ORGANIC COMPOUNDS

VII. HEAVY METALS

VIII. CONTAMINATED TRANSPORTVESSELS

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 49 - Threats to Wildlife by Chemical Warfare Agents

I. INTRODUCTION

II. BACKGROUND

III. WILDLIFE PROBLEMS OCCURRINGAFTER A TERRORIST ATTACK

IV. ILLICIT AND RESTRICTEDSUBSTANCES

V. CYANIDE

VI. RICIN (CASTOR BEAN)

VII. PESTICIDES

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

SECTION VI Toxicokinetics and Physiologically Based Pharmacokinetics

CHAPTER 50 Toxicokinetics of Chemical Warfare Agents: Nerve Agents and Vesicants

I. INTRODUCTION

II. Overview Of Invasion Processes Of Chemical Warfare Agents

III. NERVE AGENTS

IV. VESICANTS

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 51 Physiologically Based Pharmacokinetic Modeling of Chemical Warfare Agents

I. INTRODUCTION

II. DEVELOPMENT OFPHYSIOLOGICALLY BASEDPHARMACOKINETIC MODELS

III. NEED FOR IMPROVED MEASURESOF CWNA EXPOSURES – USE OF PBPKANALYSIS OF DATA

IV. PBPK SIMULATION OFCHOLINESTERASE INHIBITIONAND REGENERATED GB

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 52 Metabolism of Warfare Nerve Agents

I. INTRODUCTION

II. CHEMICAL ASPECTS OFMETABOLISM OF NERVE AGENTS

IV. OTHER FACTORS INVOLVEDIN METABOLISM AND DETOXIFICATIONOF NERVE AGENTS

V. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

SECTION VII Analytical Methods, Biosensors, and Biomarkers

CHAPTER 53 On-Site Detection of Chemical Warfare Agents

I. INTRODUCTION

II. PROPERTIES OF CHEMICALWARFARE AGENTS

III. CONCEPT OF ON-SITE DETECTION

IV. THE PRESENT SITUATIONOF THE DETECTION TECHNOLOGY

V. COMPARISON OF THE EXISTINGON-SITE DETECTION TECHNOLOGIES

VI. DEVELOPMENT OF NEW ON-SITEDETECTION TECHNOLOGIES

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 54 Laboratory Analysis of Chemical Warfare Agents and Metabolites in Biomedical Samples

I. INTRODUCTION

II. NERVE AGENTS

III. SULFUR MUSTARD AND LEWISITE

IV. CONCLUDING REMARKS ANDFUTURE DIRECTION

References

CHAPTER 55 Biosensors for the Detection of OP Nerve Agents

I. INTRODUCTION

II. BIOSENSORS

III. ELECTROCHEMICAL BIOSENSORSFOR DETECTING ORGANOPHOSPHORUSCOMPOUNDS

IV. MISCELLANEOUS BIOSENSORS FOROP DETECTION

V. CONCLUDING REMARKS ANDFUTURE DIRECTION

References

CHAPTER 56 Biomarkers of Exposure to Organophosphorus Poisons: A New Motif for Covalent Binding to Tyrosine in Proteins that have No Active Site Serine

I. INTRODUCTION

II. USE OF ACETYLCHOLINESTERASEAND BUTYRYLCHOLINESTERASEBIOMARKERS IN THE CLINIC

III. METHODS TO DETECT OP ADDUCTSON ACETYLCHOLINESTERASE ANDBUTYRYLCHOLINESTERASE

IV. WHY ARE NEW BIOMARKERSNEEDED?

V. NEW BIOMARKERS IN ANIMALS

VI. COVALENT BINDING OF OPTO TYROSINE

VII. MOTIF FOR OP BINDINGTO TYROSINE

VIII. CHARACTERISTICS OF OP BINDINGTO TYROSINE

IX. METHODS FOR DETECTING OPBINDING TO TYROSINE

X. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 57 Biomarkers and Biosensors of Delayed Neuropathic Agents

I. INTRODUCTION

II. OP COMPOUNDS

III. OPIDN

IV. NTE

V. KINETICS OF OP INHIBITOR–SERINEHYDROLASE INTERACTIONS

VI. BIOMARKERS

VII. BIOSENSORS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 58 Monitoring of Blood Cholinesterase Activity in Workers Exposed to Nerve Agents

I. INTRODUCTION

II. DETERMINATION OFCHOLINESTERASES

III. FACTORS INFLUENCING ACTIVITYOF CHOLINESTERASES

IV. DIAGNOSIS OF OP POISONING

V. MONITORING OF BLOODCHOLINESTERASE ACTIVITYIN WORKERS WITH NERVE AGENTS

VI. CONCLUDING REMARKS ANDFUTURE DIRECTION

Acknowledgments

References

SECTION VIII Prophylactic, Therapeutic, and Countermeasures

CHAPTER 59 Strategies to Enhance Medical Countermeasures After the Use of Chemical Warfare Agents on Civilians

I. INTRODUCTION

II. SCOPE OF RESEARCH

III. COUNTERACT PROGRAMSTRUCTURE

IV. THE CIVILIAN THREAT SPECTRUMAND SPECIAL CONCERNS

V. PRETREATMENTS

VI. POST-EXPOSURE PRE-TARGETPROPHYLACTIC THERAPIES

VII. POST-EXPOSURE POST-TARGETTREATMENT

VIII. DIAGNOSTIC TECHNOLOGIES

IX. BASIC/MECHANISTIC RESEARCHAND TARGET IDENTIFICATION

X. IN VITRO AND ANIMAL MODELSFOR EFFICACY SCREENING

XI. ADVANCED PRECLINICALDEVELOPMENT AND CLINICAL STUDIES

XII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 60 Medical Countermeasures and Other Therapeutic Strategies for Sulfur Mustard Toxicity

I. INTRODUCTION

III. TREATMENT OF SKIN INJURIES

II. SKIN DECONTAMINATION

IV. TREATMENT OF LUNG LESIONS

V. TREATMENT OF EYE LESIONS

VI. TREATMENT OF SYSTEMIC EFFECTS

VII. SM-INDUCED OXIDATIVE STRESSAND ITS PROTECTION

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 61 Medical Management of Chemical Toxicity in Pediatrics

I. INTRODUCTION

II. BACKGROUND

III. HISTORY OF PEDIATRIC CHEMICALCASUALTIES

IV. CHALLENGES TO MANAGINGPEDIATRIC CHEMICAL CASUALTIES

V. EFFECTS OF SPECIFIC AGENTS

VI. DECONTAMINATION OF CHILDREN

VII. PREPARATION FOR ACHEMICAL EVENT

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 62 Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling of Countermeasures to Nerve Agents

I. INTRODUCTION

II. BACKGROUND

III. CURRENT COUNTERMEASURES

IV. NOVEL COUNTERMEASURES

V. PBPK/PD MODELING

VI. DEVELOPMENT OF PBPK/PDMODELS

VII. EXPERIMENTAL ANDQUANTITATIVE STRUCTURE–ACTIVITYRELATIONSHIP (QSAR)METHODOLOGIES TO PREDICT BLOODAND TISSUE PARTITION COEFFICIENTS

VIII. INTERACTION PBPK/PD MODELFOR NAs AND COUNTERMEASURES

IX. HEALTH EFFECTS ASSESSMENT ANDCOUNTERMEASURE OPTIMIZATION

X. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 63 Prophylactic and Therapeutic Measures in Nerve Agent Poisoning

1. INTRODUCTION

II. BACKGROUND

III. MECHANISM OF ACTION

IV. PROPHYLACTIC MEASURES

V. THERAPEUTIC MEASURES

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 64 Pharmacological Prophylaxis Against Nerve Agent Poisoning: Experimental Studies and Practical Implications

I. INTRODUCTION

II. PROTECTION OF AChE AGAINSTINHIBITION

III. SCAVENGERS

IV. PROPHYLAXIS WITH CURRENTANTIDOTES

V. PROPHYLACTIC USE OFOTHER DRUGS

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 65 Pyridinium Oximes as Cholinesterase Reactivators in the Treatment of OP Poisoning

I. INTRODUCTION

II. INTERACTION OFCHOLINESTERASES WITHORGANOPHOSPHATES

III. CLINICAL ASPECTS OF ACUTE OPPOISONING

IV. ANTIDOTES IN THE TREATMENTOF OP POISONING

V. PYRIDINIUM OXIMES USED IN THETREATMENT OF POISONING WITHNERVE AGENTS AND THEIR EFFICACY

VI. EFFICACY OF PYRIDINIUM OXIMESIN POISONING WITH OP PESTICIDES

VII. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 66 Novel Oximes

I. INTRODUCTION

II. ORGANOPHOSPHORUSACETYLCHOLINESTERASE INHIBITORS

III. ACETYLCHOLINESTERASE(AChE

IV. ANTIDOTES FOR AChE INHIBITINGORGANOPHOSPHORUS POISONING

V. SYNTHESIS OF NEW AChEINHIBITORS

VI. IN VITRO EVALUATION OFSELECTED AChE REACTIVATORS

VII. STRUCTURE–ACTIVITYRELATIONSHIP OF AChEREACTIVATORS

VIII. PROMISING OXIMES

IX. NEW TRENDS IN DEVELOPMENTOF NEW AChE REACTIVATORS

X. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 67 Paraoxonase (PON1) and Detoxication of Nerve Agents

I. INTRODUCTION

II. PON1 POLYMORPHISMS: DEFININGPON1 STATUS

III. PON1 AND THE TOXICITYOF OP INSECTICIDES

IV. PON1 AND THE TOXICITY OF NERVEAGENTS

V. PON1 AS A THERAPEUTIC AGENT

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

CHAPTER 68 Role of Carboxylesterases in Therapeutic Intervention of Nerve Gas Poisoning

I. INTRODUCTION

II. ENZYMOLOGY

III. ORIGIN OF PLASMACARBOXYLESTERASE

IV. ROLE OF PLASMACARBOXYLESTERASE

V. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 69 Protection of Acetylcholinesterase from Organophosphates: Kinetic Insight into Bioscavengers

I. INTRODUCTION

II. PROTECTIVE BIOSCAVENGERS

III. DEVELOPMENT OF ATOXICOKINETIC PROTECTION ASSAY

IV. KINETIC RELEVENCE – EFFICACYIN PROTECTION

V. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgment

References

CHAPTER 70 Catalytic Bioscavengers: The Next Generation of Bioscavenger-Based Medical Countermeasures

I. INTRODUCTION

II. STOICHIOMETRIC SCAVENGERS

III. CATALYTIC SCAVENGERS

IV. REQUIREMENTS

V. POTENTIAL ENZYMES

VI. CONCLUDING REMARKSAND FUTURE DIRECTION

Acknowledgments

References

SECTION IX Decontamination of Chemical Warfare Agents

CHAPTER 71 Rapid Decontamination of Chemical Warfare Agents

I. INTRODUCTION

II. THE NATURE OF HUMAN SKIN

III. ORGANOPHOSPHATE NERVEAGENTS

IV. VESICATING AGENTS (DISTILLEDSULFUR MUSTARD, HD

V. MODEL SYSTEMS TO MEASUREABSORPTION, REMOVAL,AND DECONTAMINATION

VI. DECONTAMINATIONREQUIREMENTS

VIII. CONCLUDING REMARKSAND FUTURE DIRECTION

References

CHAPTER 72 Detoxification of Arsenic

I. INTRODUCTION

II. ARSENIC IN THE ENVIRONMENT

III. BIOLOGICAL PROPERTIESOF ARSENIC

IV. MICROBIAL TRANSFORMATIONSOF ARSENIC

V. GENES ASSOCIATED WITH ARSENICRESISTANCE MECHANISM

VI. ENHANCED ARSENICACCUMULATION IN BACTERIAL CELLS

VII. PROTEINS INVOLVED IN ARSENICRESISTANCE

VIII. POTENTIAL APPLICATIONFOR BIOREMEDIATION OFCONTAMINATED SITES

IX. CONCLUDING REMARKSAND FUTURE DIRECTION

References

Index

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