CHEMICAL WARFARE AGENTS TOXICOLOGY AND TREATMENT SECOND EDITION Editors TimothyC.Marrs,OBEMDDScFRCPFRCPath EdentoxAssociates,Edenbridge,Kent,UK NationalPoisonsInformationServiceBirminghamCentre,CityHospital,Birmingham,UK UniversityofCentralLancashire,Preston,UK RobertL.Maynard,CBEFRCPFRCPath HealthProtectionAgency,Chilton,UK FrederickR.SidellMD InstituteofChemicalDefense,AberdeenProvingGround,Maryland,USA CHEMICAL WARFARE AGENTS TOXICOLOGY AND TREATMENT SECOND EDITION CHEMICAL WARFARE AGENTS TOXICOLOGY AND TREATMENT SECOND EDITION Editors TimothyC.Marrs,OBEMDDScFRCPFRCPath EdentoxAssociates,Edenbridge,Kent,UK NationalPoisonsInformationServiceBirminghamCentre,CityHospital,Birmingham,UK UniversityofCentralLancashire,Preston,UK RobertL.Maynard,CBEFRCPFRCPath HealthProtectionAgency,Chilton,UK FrederickR.SidellMD InstituteofChemicalDefense,AberdeenProvingGround,Maryland,USA CopyrightC 2007 JohnWiley&SonsLtd,TheAtrium,SouthernGate,Chichester, (cid:2) WestSussexPO198SQ,England Telephone(+44)1243779777 Email(forordersandcustomerserviceenquiries):[email protected] Visit our Home Page on www.wileyeurope.com or www.wiley.com AllRightsReserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystemortransmittedinanyform orbyanymeans,electronic,mechanical,photocopying,recording,scanningorotherwise,exceptunderthetermsofthe Copyright,DesignsandPatentsAct1988orunderthetermsofalicenceissuedbytheCopyrightLicensingAgencyLtd, 90TottenhamCourtRoad,LondonW1T4LP,UK,withoutthepermissioninwritingofthePublisher.Requeststothe PublishershouldbeaddressedtothePermissionsDepartment,JohnWiley&SonsLtd,TheAtrium,SouthernGate, Chichester,WestSussexPO198SQ,England,[email protected],orfaxedto(+44)1243770620. 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III.Sidell,FrederickR. IV.Marrs,TimothyC.Chemicalwarfareagents. [DNLM:1.ChemicalWarfareAgents. 2.WoundsandInjuries–chemicallyinduced. 3.WoundsandInjuries–therapy. QV663C51782007] RA648.M372007 615.9–dc22 2006022729 BritishLibraryCataloguinginPublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN978-0-470-01359-5 Typesetin10/12ptTimesbyAptaraInc.,NewDelhi,India PrintedandboundinGreatBritainbyAntonyRoweLtd,Chippenham,Wiltshire Thisbookisprintedonacid-freepaperresponsiblymanufacturedfromsustainableforestry inwhichatleasttwotreesareplantedforeachoneusedforpaperproduction. CONTENTS ListofContributors vii Preface xi 1 OpinionsofChemicalWarfare 1 RobertL.Maynard 2 ThePhysicochemicalPropertiesandGeneralToxicologyofChemicalWarfareAgents 21 RobertL.Maynard 3 DispersionandModellingoftheSpreadofChemicalWarfareAgents 67 RogerD.KingdonandStephenWalker 4 TheFateofChemicalWarfareAgentsintheEnvironment 89 SylviaS.Talmage,NancyB.Munro,AnnettaP.Watson, JosephF.KingandVeroniqueD.Hauschild 5 BiologicalMarkersofExposuretoChemicalWarfareAgents 127 RobinM.BlackandDaanNoort 6 RespiratoryProtection 157 AnthonyWetherellandGeorgeMathers 7 RespondingtoChemicalTerrorism:OperationalPlanningandDecontamination 175 GronRobertsandRobertL.Maynard 8 ToxicologyofOrganophosphateNerveAgents 191 TimothyC.Marrs 9 AHistoryofHumanStudieswithNerveAgentsbytheUKandUSA 223 FrederickR.Sidell 10 NerveAgents:Low-DoseEffects 241 LeahScott 11 ManagingCivilianCasualtiesAffectedbyNerveAgents 249 J.AllisterVale,PaulRiceandTimothyC.Marrs 12 TheManagementofCasualtiesFollowingToxicAgentRelease:TheApproach AdoptedinFrance 261 DavidJ.Baker 13 TheDarkMorning:TheExperiencesandLessonsLearnedfromtheTokyo SubwaySarinAttack 277 TetsuOkumura,TomohisaNomura,ToshishigeSuzuki,ManabuSugita, YasuoTakeuchi,ToshioNaito,SumieOkumura,HiroshiMaekawa, ShinichiIshimatsu,NobukatsuTakasu,KunihisaMiuraandKouichiroSuzuki vi CONTENTS 14 AtropineandOtherAnticholinergicDrugs 287 JohnH.McDonoughandTsung-MingShih 15 Oximes 305 PeterA.EyerandFranzWorek 16 TheUseofBenzodiazepinesinOrganophosphorusNerveAgentIntoxication 331 TimothyC.MarrsandÅkeSellstro¨m 17 PretreatmentforNerveAgentPoisoning 343 LeahScott 18 GulfWarSyndrome 355 SimonWesselyandMathewHotopf 19 MustardGas 375 RobertL.Maynard 20 DermalAspectsofChemicalWarfare 409 RobertP.Chilcott 21 SulphurMustardInjuriesoftheSkin:PathophysiologyandClinical ManagementofChemicalBurns 423 PaulRice 22 TheNormalBoneMarrowandManagementofToxin-InducedStemCellFailure 443 JenniferG.Treleaven 23 OrganicArsenicals 467 TimothyC.MarrsandRobertL.Maynard 24 Phosgene 477 RobertL.Maynard 25 Cyanides:ChemicalWarfareAgentsandPotentialTerroristThreats 495 BryanBallantyne,ChantalBismuthandAlanH.Hall 26 RiotControlAgentsinMilitaryOperations,CivilDisturbanceControlandPotential TerroristActivities,withParticularReferencetoPeripheralChemosensoryIrritants 543 BryanBallantyne 27 RicinandAbrinPoisoning 613 SallyM.Bradberry,J.MichaelLord,PaulRiceandJ.AllisterVale 28 TheTotalProhibitionofChemicalWeapons 633 GrahamS.Pearson 29 AnA–ZofCompoundsofInterestinRelationtoChemicalWarfareandOther MalevolentUsesofPoisons 663 PhilippaEdwardsandRobertL.Maynard Index 709 LIST OF CONTRIBUTORS DavidJ.Baker VeroniqueD.Hauschild SAMUdeParis,ServiceduProfesseurPierre USEnvironmentalProtectionAgency, Carli,HoˆpitalNeckerEnfants–Malades, Washington,DC20460,USA 149RuedeSevres,75743Paris,France MathewHotopf BryanBallantyne InstituteofPsychiatry,King’sCentrefor 871ChappellRoad,Charleston, MilitaryHealthResearch,WestonEducation WV25304,USA Centre,King’sCollegeLondon,Cutcombe Road,London,SE59RJ,UK ChantalBismuth HoˆpitalFernandWidal,200Ruedu ShinichiIshimatsu Faubourg-Saint-Denis,75010Paris,France StLuke’sInternationalHospital,Akashicho9-1 Chio,Tokyo104-850,Japan RobinM.Black DefenceScienceandTechnologyLaboratory, JosephF.King PortonDown,Salisbury,Wiltshire, USArmyEnvironmentalCenter,Aberdeen SP40JQ,UK ProvingGround,MD21010-5400,USA SallyM.Bradberry RogerD.Kingdon NationalPoisonsInformationService PhysicalSciencesDepartment,Defence (BirminghamCentre)andWestMidlands ScienceandTechnologyLaboratory, PoisonsUnit,CityHospital,Birmingham, PortonDown,Salisbury,Wiltshire, B187QH,UK SP40JQ,UK RobertP.Chilcott J.MichaelLord ChemicalHazardsandPoisonsDivision,Centre DepartmentofBiologicalSciences,University forRadiation,ChemicalandEnvironmental ofWarwick,Coventry,Warwickshire, Hazards,HealthProtectionAgency,Chilton, CV47AL,UK Didcot,Oxfordshire,OX110RQ,UK HiroshiMaekawa PhilippaEdwards AdvancedEmergencyMedicalCenter, ChemicalHazardsandPoisonsDivision,Centre JuntendoShizuokaHospital,Nagoka1129, forRadiation,ChemicalandEnvironmental IzunokuniCity,Shizuoka410-2295, Hazards,HealthProtectionAgency,Chilton, Japan Didcot,Oxfordshire,OX110RQ,UK TimothyC.Marrs PeterA.Eyer EdentoxAssociates,Pinehurst,FourElms Walther-Straub-InstituteofPharmacologyand Road,Edenbridge,KentTN86AQ,UK; Toxicology,Ludwig-MaximiliansUniversity, NationalPoisonsInformationService Goethestrasse33,D-80336Munich,Germany (BirminghamCentre)andWestMidlands AlanH.Hall PoisonsUnit,CityHospital,BirminghamB18 ToxicologyConsultingandMedicalTranslating 7QH,UK;LancashireSchoolofHealthand Services,Inc.,(TCMS,Inc.),ElkMountain, PostgraduateMedicine,UniversityofCentral WY82324,USA Lancashire,Preston,PR12HE,UK