Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page i 15.11.2007 11:57am CompositorName:VAmoudavally Second Edition Chemical Warfare Agents Chemistry, Pharmacology, Toxicology, and Therapeutics Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page ii 15.11.2007 11:57am CompositorName:VAmoudavally 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 CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2008 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4200-4661-8 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. 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 http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com 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. Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page vi 15.11.2007 11:57am CompositorName:VAmoudavally Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page vii 15.11.2007 11:57am CompositorName:VAmoudavally 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 vii Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page viii 15.11.2007 11:57am CompositorName:VAmoudavally viii 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 Romano/ChemicalWarfareAgents:Chemistry,Pharmacology,Toxicology,andTherapeutics 46616_C000 FinalProof page ix 15.11.2007 11:57am CompositorName:VAmoudavally ix 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