Second Edition Chemical Warfare Agents

734 Pages·2008·6.88 MB·English

Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page iii 15.11.2007 11:57am CompositorName:VAmoudavally
Second Edition
Chemica l
Warfare Agents
Chemistry, Pharmacology,
Toxicology, and Therapeutics
Edited by
James A. Romano, Jr.
Brian J. Lukey
Harry Salem
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page iv 15.11.2007 11:57am CompositorName:VAmoudavally
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Library of Congress Cataloging-in-Publication Data
Chemical warfare agents : chemistry, pharmacology, toxicology, and therapeutics / editors, James A.
Romano Jr. and Brian J. Lukey. -- 2nd ed.
p. ; cm.
Rev. ed. of: Chemical warfare agents : toxicity at low levels / edited by Satu M. Somani, James A.
Romano, Jr.
Includes bibliographical references and index.
ISBN 978-1-4200-4661-8 (alk. paper)
1. Chemical agents (Munitions) I. Romano, James A. II. Lukey, Brian J.
[DNLM: 1. Chemical Warfare Agents--poisoning. 2. Disaster Planning--methods. 3.
Poisoning--prevention & control. 4. Poisoning--therapy. QV 663 C5177 2008]
RA648.C546 2008
363.17’9--dc22 2007027747
Visit the Taylor & Francis Web site at
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Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page v 15.11.2007 11:57am CompositorName:VAmoudavally
Dedication
The editors consider it a distinct honor to dedicate this
book to the memory of our good friends and distinguished
colleagues, Drs. Satu Somani and Brennie E. Hackley Jr.
Dr. Somani,professorofpharmacologyandtoxicologyatSouthernIllinoisUniversity (SIU) since
1974, was internationally recognized as a scholar and educator, as well as a pharmacologist and
toxicologist. He was dedicated to research and teaching, as well as to his students and his native
India. He was a driving force in the planning of the 35th Annual Conference of the Indian
Pharmacology Society on ‘‘Chemical and Biological Warfare’’ (CBW). He edited two books in
the area of CBW, including the first edition of this work with James Romano in 2001. He was
particularly devoted to working with medical students in India in implementing problem-based
learning.Thisphilosophy,althoughnewtoIndia’smedicalschools,wasacorephilosophyatSIU.
Conversely, he was eager to incorporate ayurvedic medicine into the medical pharmacology
curriculum at SIU. Although Dr. Somani passed away on October 29, 2002, he remains a source
of inspiration tothe editors.
Dr. Brennie E. Hackley Jr. was chief scientist and scientific advisor to the commander of the
United States Army Medical Research Institute of Chemical Defense. He authored or coauthored
more than 75 publications and 15 U.S. patents. His publications and patents contributed signifi-
cantly to the development of medical antidotes for chemical warfare agents. During his career,
Dr. Hackley studied the relationship between chemical structures and chemotherapeutic activity
withreferencetoefficacyagainsttoxicagents.Hecontributedtotheelucidationofmechanismsof
reactionsofnucleophileswithorganophosphoruscompounds.Hesynthesizedanumberofoximes,
one ofwhichwas adopted as an antidote against chemical agents by theU.S. AirForce.
Dr. Hackley received numerous honors and commendations during 57 years of his continuous
governmentservice.HewasanhonorarylifememberoftheAmericanChemicalSocietyandfellow
of theAmerican Instituteof Chemists. Dr. Hackley passed away onNovember 5,2006.
The field of medical chemical defense will struggle to overcome the loss of Drs. Somani and
Hackley, but in the end will prevail because of their legacy of scholarly effort and compassionate
mentoring.
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Contents
Preface..............................................................................................................................................xi
Acknowledgments.........................................................................................................................xvii
Editors............................................................................................................................................xix
Contributors...................................................................................................................................xxi
Chapter 1 Brief History andUse ofChemical Warfare AgentsinWarfare
andTerrorism...............................................................................................................1
Harry Salem, Andrew L. TernayJr., and Jeffery K. Smart
Chapter 2 Chemistry ofChemical Warfare Agents...................................................................21
Petr Kikilo, Vitaly Fedorenko, and Andrew L. TernayJr.
Chapter 3 ChemicalWarfareAgentThreatto DrinkingWater.................................................51
Harry Salem, ChristopherE.Whalley, Charles H.Wick,
ThomasP.Gargan II,and W. Dickinson Burrows
Chapter 4 Health Effects ofLow-Level Exposure to Nerve Agents.........................................71
John H.McDonoughand JamesA. Romano Jr.
Chapter 5 Toxicokinetics ofNerveAgents................................................................................97
MarcelJ. van derSchans,Hendrik P.Benschop, and ChristopherE.Whalley
Chapter 6 Application ofGenomic,Proteomic,and Metabolomic Technologies
tothe Developmentof Countermeasures againstChemical
Warfare Agents........................................................................................................123
Jennifer W. Sekowski and JamesF. Dillman III
Chapter 7 Novel Approaches toMedicalProtection against Chemical Warfare
Nerve Agents...........................................................................................................145
Ashima Saxena, ChunyuanLuo,Nageswararao Chilukuri,
DonaldM. Maxwell,and Bhupendra P.Doctor
Chapter 8 Nerve AgentBioscavengers:Progress inDevelopment ofa New Mode
ofProtection againstOrganophosphorus Exposure................................................175
David E.Lenz, Clarence A.Broomfield,David T. Yeung,Patrick Masson,
DonaldM. Maxwell,and Douglas M.Cerasoli
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Chapter 9 Butyrylcholinesterase and Its SyntheticC-Terminal Peptide Confer
In Vitro Suppression of Amyloid Fibril Formation..............................................203
Erez Podoly, Sophia Diamant, Assaf Friedler, Oded Livnah,
and Hermona Soreq
Chapter 10 NovelMedicalCountermeasurefor Organophosphorus Intoxication:
Connection toAlzheimer’s Disease and Dementia...............................................219
EdnaF.R. Pereira,DavidR. Burt,YascoAracava,Robert K. Kan,
Tracey A.Hamilton,JamesA.RomanoJr., MichaelAdler,
and Edson X.Albuquerque
Chapter 11 Inhalation Toxicologyof NerveAgents................................................................233
PaulA.Dabisch, StanleyW. Hulet, Robert Kristovich,
and Robert J.Mioduszewski
Chapter 12 Vesicantsand Oxidative Stress.............................................................................247
Milton G.Smith, WilliamStone, Ren-Feng Guo, Peter A.Ward,
Zacharias Suntres, Shyamali Mukherjee, and Salil K. Das
Chapter 13 Health Effects of Exposure toVesicant Agents....................................................293
Charles G.Hurst and William J.Smith
Chapter 14 Cyanides:Toxicology, ClinicalPresentation, and Medical Management............313
Bryan Ballantyne andHarrySalem
Chapter 15 Chemicals Usedfor Riot Control andPersonal Protection...................................343
HarrySalem,BryanBallantyne, andSidney Katz
Chapter 16 Mechanism of Action of Botulinum Neurotoxin andOverview
of Medical Countermeasures forIntoxication.......................................................389
MichaelAdler, George Oyler,JamesP.Apland,Sharad S. Deshpande,
JamesD. Nicholson, Jaime Anderson, Charles B.Millard,
and Frank J. Lebeda
Chapter 17 Ricin andRelated Toxins: Review and Perspective.............................................423
Charles B.MillardandRossD.LeClaire
Chapter 18 Screening Smokes: Applications, Toxicology, Clinical Considerations,
and Medical Management.....................................................................................469
Bryan Ballantyne andHarrySalem
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Chapter 19 Clinical Detection of Exposure toChemical Warfare Agents..............................501
Benedict R.Capacio, J.RichardSmith, Richard K. Gordon,
Julian R.Haigh,John R.Barr,and Brian J.Lukey
Chapter 20 PersonalProtective Equipment: Practicaland TheoreticalConsiderations...........549
MichaelR.Jones
Chapter 21 ChemicalWarfareAgent Decontamination from Skin.........................................611
Brian J.Lukey,Harry F.Slife Jr., Edward D.Clarkson,Charles G.Hurst,
and Ernest H. Braue Jr.
Chapter 22 ChemicalWarfare,Chemical Terrorism, and Traumatic Stress Responses:
AnAssessmentof Psychological Impact..............................................................627
JamesA.Romano Jr., Lucille A.Lumley, JamesM. King,
and George A.Saviolakis
Chapter 23 Emergency Response toa ChemicalWarfareAgent Incident:
DomesticPreparedness, First Response, andPublic Health Considerations........653
David H.Moore and Barbara B.Saunders-Price
Chapter 24 Emergency Medical Response toa ChemicalTerroristAttack............................675
Stephen A.Pulley and MichaelR.Jones
Index.............................................................................................................................................713
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Preface
We previously published a book on chemical warfare agents (CWAs) in 2001. There have been
manychangesinthisareainpastyears,drivenbyworldeventsthathavecreatedasenseofurgency
tothisfield.Webelieveitistimetoupdateourpreviouswork,citingthenumerousdevelopmentsin
the field since 2001. We believe these to include epidemiological or clinical studies of exposed or
potentiallyexposedpopulations,newtreatmentconceptsandproducts,improvedorganizationofthe
national response apparatus in the United States to address the potential for CWA terrorism, and
improved diagnostic tests that enable rapid diagnosis and treatment. In the preface to our earlier
work,weprovidedarationaleastowhyanincreasednationalinvestmenthadbegunintheUnited
States.Thatpreface was written inJanuary 2001.
As in our earlier work, we consider our chapter contributors to be experts who are recognized
fortheircontributionstothescienceoftoxicchemicals.Theircontributionsaresummarizedinthe
followingparagraphs.
Salem, Ternay, and Smart tell us that chemicals have been used in warfare since almost the
beginning of recorded history. Use of chemicals started out crudely using malodorous materials,
irritants, poisonous plants and animals, as well as decaying bodies. Since the birth of chemistry,
toxic chemicals have been created specifically for war. Lethal and disabling chemicals were
developed, which incapacitated or killed the enemy without disfiguring or mutilating the body
and without affecting or destroying the infrastructure. These chemicals appeared to offer distinct
advantages.Itisimportanttorecognizethattheadvancesinbiotechnology,nanotechnology,genetic
engineering, neurobiology, and computer sciences, among others, may assist not only in the
proliferation of traditional CWAs, but also stimulate the emergence of nontraditional agents as
well. Advances have also occurred in thedelivery systems ofthese agents. The authors concluded
that while the use of CWAs in terrorist activities appears to have been limited, this may not
accuratelyreflect thepotential oftheirfuture use.
Kikilo, Fedorenko, and Ternay provide an overview of the chemistry of selected substances
that have been thought of as CWAs at one time or another. In general, this chapter is written
fromtheperspectiveofanorganicchemist.Theauthorsbeginwithsomegeneralremarksregarding
nomenclature and categories, followed by discussions of physical properties, synthesis, and
chemical reactions. This chapter covers the chemistry of pulmonary (choking), asphyxiating
(blood), nerve, and blister agents, as well as a brief discussion of incapacitating (one instance)
and riot-control agents (one instance).
Salem,Whalley,Wick,Gargan,andBurrowspointoutthatwatersuppliesandtheirdistribution
systemsarepotentialtargetsforterroristactivityintheUnitedStates.Evenshort-termdisruptionof
water service can significantly impact a community and lead to serious medical, public health,
societal,andeconomicconsequences.IntheUnitedStates,mostofthewatersupplyistreatedand
contains a disinfectant, such as free chlorine or chloramines, to destroy or control the growth of
bacteria. Maintaining a residual free chlorine concentration of 0.5 mg=L for public water supplies,
and2.0mg=Lfor fielddrinkingwater fordeployedtroopscould provideadequateprotectionfrom
most biological contamination. The authors considered chemical threats to the water supply and
concludedthatalthoughitmaybepossibletocontaminateawatersupplysystem,ahighdegreeof
physical security, combined with maintaining a higher-than-usual residual chlorine level, should
ensure itssafety.
McDonough and Romano provide an update of their earlier contribution on ‘‘Health Effects
of Low-Level Exposure to Nerve Agents.’’ They bring this area up-to-date by reviewing
epidemiologicalorclinicalstudiesofexposedorpotentiallyexposedpopulationsandnewtreatment
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concepts and products to mitigate nerve agent toxicity. They point out the significant human
epidemiological and clinical literature that has appeared since 2001. These studies are based on
furtherfollow-upofmilitaryvolunteersfromearlierresearchprogramsintheUnitedStatesandthe
UnitedKingdom,andmoreintensivefollow-upofthevictimsofJapaneseterroristattacksinvolving
nerveagentsin1994and1995.Theyconcludebydiscussingfournewpotential‘‘productlines’’of
improved treatment forthese deadly nerve gases.
VanderSchansandBenschoppresenttherationalefortoxicokinetic=toxicodynamicstudiesof
nerve agents. They argue that toxicokinetic studies are of ultimate importance because the time
periodoftheintoxicationbynerve agents,perhaps contrarytoearlier thinking, might spanseveral
hours. This suggests that the timing of the antidote administration has to be adapted to the
toxicokinetic process. A section discussing the importance of distinguishing the stereoisomers of
nerveagentsprecedesthediscussionofthetoxicokineticsofnerveagents.Thedistributionofsarin
throughtissuesisdiscussedaspartofacharacterizationoftheeliminationpathwaysofnerveagents.
Finally, the toxicokinetics of soman in anesthetized, atropinized, and artificially ventilated, naive,
and HuBuChE-pretreated guinea pigs were studied, demonstrating the utility of the toxicokinetic
approach inevaluating the effectiveness ofscavengers.
Sekowski and Dillman tell us that over the past several years, there has been a move away
from a reductionist approach of studying one gene or protein at a time toward a more global
approachofstudyingmolecularandcellularnetworksandhowthesenetworksintegrateinformation
and respond to the environment. Recent technological developments allow researchers to study
the function of a single gene or protein in the context of cellular and molecular networks, or to
study the response of numerous genes or proteins to an environmental stimulus (e.g., CWA
exposure).Thesenewmoleculartechniquesallowforglobalanalysisofgeneexpression(genomics,
transcriptomics), global analysis of protein expression, modification, function (proteomics), and
global analysis of metabolism and metabolites (metabonomics, metabolomics). Within the Army
lifescienceresearchcommunity,SekowskiandDillmanandmanyoftheircolleaguesarefollowing
theleadofthepharmaceuticalandbiotechnologyindustriesinapplyingtheseglobalapproachesand
associated technologies to the problem of CWA countermeasures. In this chapter, they provide an
overview of each of these technologies and their current state-of-the-art, and provide examples of
how these approaches arebeing applied tothe development of CWA countermeasures.
Saxena, Luo, Chilukuri, Maxwell, and Doctor describe novel approaches to medical pro-
tection against CWAs. They begin by discussing enzyme-based pretreatments, to include
both stoichiometric and catalytic scavenging enzymes, their isolation and purification, and the
like. Interestingly, the authors speculate on the delivery of scavenging enzymes by gene therapy
and carefully describe the benefits of that approach. Next, they consider advances in oxime-
based, postexposure therapy, going beyond the treatment offered by McDonough and Romano in
consideringevenmorerecentlysynthesizedagentscomparableto,orperhapssuperiorto,MMB-4.
Finally, they consider centrally acting pretreatment drugs. They agree with the sentiment of
Periera et al. in that a number of centrally acting pretreatments, many designed for treatment
ofAlzheimer’sdisease,andclearlysuperiortopyridostigminebromide,areemergingfromresearch
in this area.
Lenz, Broomfield, Yeung, Masson, Maxwell, and Cerasoli describe the use of scavenger
enzymes as alternatives to conventional approaches to the management of nerve agent casualties.
Thisapproach,describedbytheminourearliervolume,avoidssideeffectsassociatedwithcurrent
multidrugantidotalregimens.Italsoobviatestherequirement,oftendifficulttoachieveinamilitary
setting, for rapid administration of pharmacologically sufficient drug to attain its therapeutic aim.
Candidate bioscavenger proteins, which react quickly, specifically, and irreversibly with organo-
phosphoruscompounds,arepresentedanddiscussed.Thisbondmaybestoichiometricandsequester
substrate or may be catalytic, hydrolyzing substrate into biologically inert products. Promising
examplesofeachapproacharepresented,andtheadvantagesofthenovelapproachoverconventional
approachesarediscussed.
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Podoly,Diamant,Friedler,Livnah,andSoreq,attheHebrewUniversityofJerusalem,demon-
strated that BuChE, in addition to its endogenous scavenging of drugs, therapeutics, and CWAs,
appearstoattenuatetheformationofamyloidfibrilsinthehumanbrain.Thus,BuChEmayprovide
neuroprotection not only in the short term, but also within a longer time frame, increasing its
potential for future therapeutic uses. These provocative findings suggest a common direction for
bothAlzheimer’sresearch and research into the protectionagainst nerve CWAs.
Pereira,Burt,Aracava,Kan,Hamilton,Romano,Adler,andAlbuquerquedescribethepossible
utility of Alzheimer’s disease drugs in protecting against central as well as peripheral effects of
nerveagents.Onesuchdrug,galantamine(alsocalledgalanthamine),hasrecentlybeenfoundbythe
authors to be a superior antidote against intoxication by soman and other nerve agents, effective
when administered both before and soon after exposure. It has been suggested that the neuropro-
tective effect of galantamine is a result of activation of a number of kinases, including the
extracellular signal-regulated kinase, secondary to the nicotinic allosteric potentiating action of
thealkaloid.ItislikelythatselectiveblockofAChEversusBuChE,abilitytopenetratetheblood–
brain barrier, and allosteric potentiation of nAChRs all contribute to the effectiveness of galanta-
mineasamedicalcountermeasureagainstorganophosphate(OP)poisoning.Thedatasummarized
here indicate that the introduction of galantamine into clinical practice for OP poisoning will
providea majoradvance.
Dabisch,Hulet,Kristovich,andMioduszewskipresentanoverviewofthetoxiceffectsassoci-
ated with inhalation of a nerve agent vapor or aerosol. Many studies cited were conducted at the
U.S.ArmyChemicalBiologicalCenterfromthe1950suptothepresentday.Theauthorspointout
thatthechallengeforlaboratorystudiesistosafelygeneratestablevapororaerosolatmospheresand
verifytheiratmosphericconcentration,chemicalcharacterization,andstabilityduringtheexposure
period.Theresultsofsuchwell-controlledstudiesenhancehumanriskassessmentmodelingtools,
supporttheoperationalriskmanagementdecisionprocess,andhelpdefinephysiologicallyrelevant
nerve agent detectionthresholds.
Smith,Stone,Guo,Ward,Suntres,Mukherjee,andDasfocusontheoxidativestressaspectsof
vesicant exposure, a subject that has received little attention previously. The authors discuss three
key intermediate mechanisms in the pathogenesis of the mustard injury—activation of PARP,
formation of toxic metabolites, and signaling pathways that invoke the action of a number of
proinflammatorymediators,lookingparticularlyatsphingomyelinase-producedceramidesasapop-
totictriggers.Theauthorsdiscussapproachestoantidotesorameliorativemeasuresforafamilyof
vesicantsandthepulmonarytoxicantschlorineandphosgene.Theresultspresentedhereprovidea
molecular and cellular basis for developing strategies for pharmacological intervention, with
potential forclinical application.
Hurst and Smith discuss the health effects of exposure to vesicant agents. They consider the
mustards (nitrogen and sulfur mustard) and lewisite. They describe the biochemical and physio-
logical rootsofthepathogenesisofthesevesicatingagents,theprincipaltargetorgans,theclinical
courseofthepathologyineachinstance,residuallong-termhealtheffects,andmedicalmanagement
ofcasualtiesofvesicant exposure.Theauthorsalso provideabriefhistory ofthecircumstancesof
exposureofhumanstovesicatingagents,whetherinwarfare,volunteersinresearch,or,inthecase
of mustards, in medical treatment. This chapter considers current research and concludes,
‘‘Although much effort is being expended in developing therapeutic interventions that will limit
theextentoftissuepathology,thebestimmediateapproachesinvolvepreventionofcontactbetween
mustard and tissues and medicalprocedures that easepatient traumaanddiscomfort.’’
BallantyneandSalemdiscusstheexperimentalandhumanclinicaltoxicologyofcyanideswith
particular reference to their potential for application as chemical warfare weapons and use by
terrorists.Theyconsiderrepeatedexposuretoxicityaswellasspecificorgan,tissue,andfunctional
end-point toxicity. Among the functional end-point toxicities, they review neurotoxicity, cardio-
toxicity, vascular toxicity, developmental and reproductive toxicity, and genotoxicity. They con-
cludethisreviewofthetoxicologyofcyanidebydescribingemergencyfirstaidandpoison-control
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measuresincurrentusageaswellnewapproaches,stillintheresearchstage,tothemanagementof
the problem ofcyanide poisoning.
Salem, Ballantyne, and Katz present the argument that when chemicals are used to control
civilian disturbances, it is necessary to use substances of low health hazard potential and employ
delivery methods that carry the minimum potential for injury. This chapter reviews the nature and
effects of chemicals used, and proposed for use in peacekeeping operations. Particular attention is
given to their operational uses in various circumstances, pharmacology, toxicology, evaluation of
safety-in-use,delivery,effectsonhumans,consequencesandmedicalmanagementofoverexposure
and injury, and theneed for preparedness planning.
Adler, Oyler, Apland, Deshpande, Nicholson, Anderson, Millard, Keller, and Lebeda use the
insightsgainedintheirunderstandingofthemechanismofbotulinumneurotoxin(BoNT)actionto
establishaconceptualframeworkwithinwhichtodevelopeffectivetreatmentstrategiesforintoxi-
cation.Theauthorsalsosuggestthatsomevaccineapproacheshaveproveneffective,butgenerally
requiremultipleinoculationsand incubationtimes ofuptoa yearfrom onset togenerateadequate
protection. In addition, vaccinated individuals may be precluded from the use of local BoNT
administration for treatment of spasticity or movement disorders that may develop during their
lifetime.Theselimitationsarguestronglyinfavorofasupplementarypharmacologicalapproachfor
the management of botulism. They point out that efforts to develop pharmacological inhibitors of
BoNThaveincreasedsubstantiallyduringthelastdecade.Themajorfocusofthecurrentresearchis
thedesignandsynthesisofspecificmetalloproteaseinhibitors.Mostoftheongoingdrugdiscovery
efforts were initiated prior to the availability of the crystal structure for BoNT and will be aided
enormously by theavailability ofprecisestructural information.
Millard and LeClaire reported that several aspects of ricin, including its significant human
toxicity, past military interest, wide availability in ton quantities from castor seed meal, and
increased attention from the world news media, have contributed to the international regulation of
thetoxin asapotential ‘‘weaponofmass destruction.’’Theyprovide anoverview ofthis literature
for scientists who are working toward practical medical solutions to prevent or mitigate the
consequences of chemical warfare or bioterrorism. They summarize the biochemistry and patho-
physiologyofricinandbrieflyreviewstudieswithexperimentalanimalmodelstoaidinpreventing,
diagnosing, and treating the poorly characterized human response to ricin exposure. Throughout
thechapter,theycomparedricintoseveralcloselyrelatedproteinstoxinsofcomparablepotencyof
thesameplantgenus.Thisisdonetoclarifythegapsinourcurrentunderstandingforthisimportant
class of plant toxins.
Ballantyne and Salem present the concept of screening smokes, for example, a fog-like
atmosphere composed of light-scattering particles that limit visibility of troops or vehicles. These
particles should not be of a biologically reactive nature, lest they be classified as CWAs under
theGenevaConvention.Intheirchapter,theydiscusstheacuteandchronictoxicity,aswellasthe
environmentalandecotoxicologicalimpact,ofthemostcommonscreeningsmokes.Theyconclude
bydiscussingthemedicalmanagementofpatientsoverexposedtoscreeningsmokes,whichcanin
rare cases cause systemictoxicity.
Capacio,Smith,Gordon,Haigh,Barr,andLukeydescribesomeofthemostrecentapproaches
to improving nerve agent diagnostics. They describe efforts to develop portable, reliable, prompt
(i.e.,nearreal-time)assayscapableofdetectingexposureevenwhenadministeredaftersometime.
They remind us that these assays are compared to the delta pH method of Ellman, the historical
standardformeasurementofChEasthebiomarkerofexposure.Lukeyandhiscolleaguespointto
successfuleffortstomeasureregeneratednerveagentinblood.Thus,giventhepotentialincreasein
urbanterrorismthatmayincludetheuseofchemicalwarfareorganophosphateagents,federal,state,
and local authorities now have a variety of sensitive and accurate cholinesterase and OP detection
assays forappropriate containment, decontamination,and treatment measures.
Jones provides an assessment of the importance of physical protection equipment in support-
ing effective prehospital interventions. He describes the requirements for, availability of, and