Handbook of Toxicology of Chemical Warfare Agents Gupta

1124 Pages·2009·39.9 MB·English

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List of Contributors
ARTURO ANADO´N, DVM, PhD, DipECVPT, Professor, ATRAYEE BANERJEE, PhD Post Doctoral Research Fellow,
Departamento de Toxicolog´ıa y Farmacolog´ıa, Facultad de Missouri University of Science and Technology, Rolla, Missouri
Veterinaria,UniversidadComplutensedeMadrid,28040-Madrid, 65401, USA
Espan˜a
CHERYL BAST, PhD, DABT Toxicology and Hazard Assess-
JAIME ANDERSON, DVM, PhD Lieutenant Colonel, Veteri- ment Group, Environmental Sciences Division, Oak Ridge
naryCorps,USArmy,Chief,AnalyticalToxicologyDivision,US National Laboratory,OakRidge, TN,USA
Army Medical Research Institute of Chemical Defense, 3100
VAL R. BEASLEY, DVM, PhD, DABVT, Professor, Department
Ricketts PointRoad, APG-EA,Maryland 21201-5400, USA
of Veterinary Biosciences, College of Veterinary Medicine,
JUN-ICHI ANZAI, PhD Graduate School of Pharmaceutical University ofIllinois, Urbana, IL,USA
Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-
8578, Japan R. BHATTACHARYA, Sci E Division of Pharmacology and
Toxicology, Defence Research and Development Establishment,
MICHAEL ASCHNER, PhD Departments of Pediatrics and Jhansi Road, Gwalior -474002,MP, India
Pharmacology, Center in Molecular Toxicology and Kennedy
Center for Research on Human Development, Vanderbilt WHITNEY BURROWS, MD Thoracic Surgeon, Greenebaum
University Schoolof Medicine,Nashville, TN 37212, USA Cancer Center, University of Maryland Medical Center, 22
S. Greene St, Baltimore, MD 21201-1595, USA and
PETER AVDONIN, MSc N.K. Koltzov Institute of Develop-
Assistant Professor of Surgery, University of Maryland School
mental Biology, Russian Academy of Sciences, ul.Vavilova #32,
of Medicine, 655 W. Baltimore St, Baltimore, MD 21201-1559,
Moscow, Russia
USA
VLADIMIR BABAKOV, PhD Research Institute of Hygiene,
ROBERT P. CASILLAS, PhD Vice President, Biomedical
Occupational Pathology and Human Ecology, Bldg 93, p.o.Kuz-
Science and Technology, Battelle Memorial Institute, 505 King
molovsky, Saint-Petersburg, 188663,Russia
Ave, 7-2,Columbus, OH43201, USA
MICHAEL C. BABIN, DVM, PhD Toxicologist, Battelle
SYLVAIN CHEMTOB Department of Pharmacology, Pediatrics
Biomedical Research Center, 505 King Avenue, Columbus, OH
and Ophthalmology,University ofMontreal, Quebec,Canada
43201-2693, USA
EDWARD D. CLARKSON, DABT, PhD Medical Toxicology
DEBASIS BAGCHI, PhD, FACN, CNS InterHealth Research
Branch, Analytical Toxicology Division, US Army Medical
Center, 5451 Industrial Way, Benicia, CA, USA and Creighton
Research Institute of Chemical Defense, 3100 Ricketts Point
University Medical Center, 2500 California Plaza, Omaha, NE,
Road, APG-EA,MD 21010-5400,USA
USA
R. W. COPPOCK, DVM, DABVT, PhD, DABT Adjunct
MANASHIBAGCHI,PhD,FACN InterHealthResearchCenter,
Professor, University of Alberta, Faculty of Medicine, Adjunct
5451Industrial Way,Benicia, CA,USA
Professor, Concordia University College, Toxicologist and Asso-
JIRIBAJGAR,MD,CSD DepartmentofToxicology,Facultyof ciates Ltd,PO Box2031, Vegreville, ABT9C 1T2,Canada
MilitaryHealthSciences,UniversityofDefense,Trebesska1575,
LUCIO G. COSTA, PhD Department of Environmental and
Hradec Kralove, CzechRepublic
OccupationalHealthSciences,UniversityofWashington,Seattle,
KULBIR BAKSHI, PhD Retired, Program Director, Committee WA, USA and Department of Human Anatomy, Pharmacology,
onToxicology,BoardonEnvironmentalStudiesandTechnology, and Forensic Science, University of Parma Medical School,
National Research Council,Washington, DC,USA Parma, Italy
FRANK BALSZUWEIT, PhD Bundeswehr Institute of Pharma- T. V. DAMODARAN, MS, Mphil, PhD Assistant Professor,
cologyandToxicology,Neuherbergstr.11,80937Munich,Germany DepartmentofMedicine,POBox3445,Room4024,GSRB1,595
xi
xii List of Contributors
SouthLaSalleStreet,DukeUniversityMedicalCenter,Durham, DANAF. GLASS, DVM Oak Ridge National Laboratory, 1060
NC 27710,USA Commerce Park,OakRidge,TN 37830,USA
WOLF-D. DETTBARN, MD Professor Emeritus, Vanderbilt NIKOLAYGONCHAROV,PhD,DrSci(Biochemistry) Research
UniversityMedicalCenter,VanderbiltUniversity,Nashville,TN, Institute of Hygiene, Occupational Pathology and Human Ecology,
USA Bldg93,p.o.Kuzmolovsky,Saint-Petersburg,188663,Russia
SERGEY DULOV, PhD Research Institute of Hygiene, Occu- MARIONK.GORDON,PhD AssociateProfessor,Department
pational Pathology and Human Ecology, Bldg 93, p.o.Kuzmo- of Pharmacology and Toxicology, Ernest Mario School of Phar-
lovsky,Saint-Petersburg, 188663, Russia macy and Environmental and Occupational Health Sciences
Institute, Rutgers University, 170 Frelinghuysen Road, Piscat-
ROBERT W. ENZENAUER, MD, MPH Professor, Department
away, NJ08854, USA
of Ophthalmology, UT Health Science Center, University of
Tennessee College of Medicine, 930 Madison, Suite 470, Mem- RICHARDK.GORDON,PhD Chief,DepartmentofRegulated
phis, TN 38103, USA and Colonel Medical Corps Senior Flight Laboratories,DivisionofRegulatedActivities,WalterReedArmy
Surgeon, Battalion Surgeon 5/19th SFG(A), Colorado Army Institute of Research, 503 Robert Grant Avenue, Silver Spring,
National Guard MD 20910-7500,USA
ELENAERMOLAEVA,MD,PhD,DrSci(Medicine) Research JOSHUAP.GRAY AssistantProfessor,DepartmentofScience,
InstituteofHygiene,OccupationalPathologyandHumanEcology, United States Coast Guard Academy, 27 Mohegan Ave, New
Bldg93,p.o.Kuzmolovsky,Saint-Petersburg,188663,Russia London, CT06320, USA
TIMOTHY J. EVANS, DVM, PhD, DABVT University of Mis- ZORAN GRUBIC, MD, PhD Professor of Pathophysiology,
souri,CollegeofVeterinaryMedicine,DeptartmentofVeterinary Laboratory for Molecular Neurobiology, Head Institute of Path-
Pathobiology Toxicology Section, PO Box 6023, Columbia, MO ophysiology, Faculty of Medicine, University of Ljubljana,
65205, USA Zaloska 4,1000Ljubljana,Slovenia
TAMA EVRON The Department of Biological Chemistry, The KAVITA GULATI Department of Pharmacology, Vallabhbhai
Hebrew Universityof Jerusalem,Jerusalem 91904,Israel Patel ChestInstitute, University ofDelhi, Delhi-110007,India
GOVINDER FLORA Health Sciences Division, Spherix Inc., RAMESH C. GUPTA, DVM, MVSc, PhD, DABT, FACT,
Bethesda, Maryland 20817,USA FATS Professor and Head, Murray State University, Breathitt
Veterinary Center, Toxicology Department, PO Box 2000; 715
S.J.S.FLORA,PhD DivisionofPharmacologyandToxicology,
North Drive, Hopkinsville, KY42240-2000,USA
DefenceResearch and DevelopmentEstablishment, Jhansi Road,
Gwalior -474002,MP, India WANDA M. HASCHEK-HOCK, BVSc, PhD, DABT, DACVP,
Professor, Department of Pathobiology, College of Veterinary
FRODEFONNUM,PhD DepartmentofBiochemistry,Institute
Medicine, University ofIllinois, Urbana,IL, USA
of Basic Medical Sciences, University ofOslo, Oslo,Norway
VERONIQUE HAUSCHILD Directorate of Occupational and
CLEMENT E. FURLONG, PhD Department of Medicine
Environmental Medicine, Environmental Medicine Program, US
(Division ofMedical Genetics)and Genome Sciences University
Army Center for Health Promotion and Preventive Medicine,
of Washington,Seattle,WA, USA
BldgE-1570,StarkRoad,AberdeenProvingGround,MD21010-
JOSEF FUSEK, PhD Department of Toxicology, Faculty of 5403, USA
MilitaryHealthSciences,UniversityofDefense,Trebesska1575,
COREY J. HILMAS, MD, PhD Research Physiologist, Neuro-
Hradec Kralove, CzechRepublic
behavioral Toxicology, US Army Medical Research Institute of
ANSHOO GAUTAM Defence Research and Development Chemical Defense, 3100 Ricketts Point Road, APG-EA, MD
Establishment, Gwalior– 474002, India 21201-5400, USA
JEFFERY M. GEARHART, PhD, DABT The Henry M. Jackson ELORA HILMAS, PharmD/BCPS Pediatric Clinical Specialist,
Foundation, Applied Biotechnology Branch, Air Force Research Pharmacy Practice Residency Coordinator, Alfred I. du Pont
Laboratory,Bldg837,2729RStreet,WrightPattersonAFB,OH Hospital for Children, 1600 Rockland Road, Wilmington, DE
45433, USA 19803, USA
DONALDR.GERECKE Associate Professor, Pharmacology and DARRYL B. HOOD, PhD Department of Neurobiology and
Toxicology,ErnestMarioSchoolofPharmacy,RutgersUniversity, Neurotoxicology, Center for Molecular and Behavioral Neuro-
170FrelinghuysenRd,410EOHSI,Piscataway,NJ08854,USA science, Meharry Medical College,Nashville, TN,USA
BRIAN C. GEYER Center for Infectious Diseases and Vacci- J. F. HUMBERT, PhD Research Director, Institut Pasteur-URA
nology, at the Biodesign Institute and School of Life Sciences, CNRS 2172, Unite´ des Cyanobacte´ries, 28 Rue Du Dr Roux,
PO Box 874501, Arizona State University, Tempe, AZ 85287- 75724 Paris Cedex 15, France, and INRA, UMR CARRTEL,
4501, USA BP511, 74203ThononCedex,France
LIDIA GLASHKINA, PhD, Research Institute of Hygiene, EDWARD M. JAKUBOWSKI US Army Edgewood Chemical
Occupational Pathology and Human Ecology, Bldg #93, BiologicalCenter,AMSRD-ECB-RT-TN,5183BlackHawkRD,
p.o.Kuzmolovsky,Saint-Petersburg, 188663, Russia APG, MD 21010-5424,USA
List ofContributors xiii
RICHARD JENKINS, PhD Professor, School of Allied Health ILIA KRASNOV, MSc Institute of Analytical Engineering,
Sciences, De MontfortUniversity, Leicester LE19BH,UK Russian Academy of Sciences, Rizhsky prosp. 26, Saint-
Petersburg, 190103,Russia
DAVID A. JETT, PhD Program Director for Counterterrorism
Research, National Institutes of Health, NINDS, 6001 Executive KAMIL KUCA, PhD Department of Toxicology, Faculty of
Blvd,NSC,Room2177,MSC9527,Bethesda,MD20892-9527, MilitaryHealthSciences,UniversityofDefense,Trebesska1575,
USA HradecKralove,CzechRepublicandCenterofAdvancedStudies,
Faculty of Military Health Sciences, University of Defense,
GEORGEC-T.JIANG ChemRiskInc.,25JessieSt,Suite1800,
Trebesska 1575,Hradec Kralove,Czech Republic
San Francisco,CA 94105, USA
SERGEYKUZNETSOV,PhD,DrSci(Physiology) I.M.Sechenov
HARALD JOHN, PD, PhD Bundeswehr Institute of Pharma-
Institute of Evolutionary Physiology and Biochemistry, Russian
cology and Toxicology, Neuherbergstr. 11, 80937 Munich,
Academy of Sciences, ul.Moriza Toreza 44, Saint-Petersburg,
Germany
194223,Russia
NATHAN H. JOHNSON, PhD Program Manager, Defense
JOSEPH C. LARSEN, PhD Program Manager, Defense Threat
Threat Reduction Agency, 8725 John J. Kingman Drive (CBM),
Reduction Agency, Fort Belvoir, VA, 8725 John J. Kingman
FortBelvoir, VA22060,USA
Drive (CBM),Fort Belvoir,VA22060,USA
MILAN JOKANOVIC´, PhD, Professor of Toxicology Experta
FRANCISC.LAU InterHealthResearchCenter,5451Industrial
Consulting, Nehruova57, 11000Belgrade,Serbia
Way,Benicia CA,USA
DHAVAL N. JOSHI, MSc (Biochemistry) Research Student,
JING LIU, PhD Department of Physiological Sciences, Center
LaboratoryofBiochemistry,B.R.D.SchoolofBiosciences,Sardar
forVeterinaryHealthSciences,OklahomaStateUniversity,USA
Patel Maidan, Vadtal Road, Satellite Campus, Post Box No. 39,
Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, OKSANA LOCKRIDGE, PhD Eppley Institute, University of
India Nebraska Medical Center, Omaha,NE68198, USA
DANIEL JUN, PhD Department of Toxicology, Faculty of BOMMANNA G. LOGANATHAN, PhD Department of
MilitaryHealthSciences,UniversityofDefense,Trebesska1575, Chemistry and Center for Reservoir Research, 456 Blackburn
HradecKralove,CzechRepublicandCenterofAdvancedStudies, Science Building, Murray State University, Murray, KY 42071,
Faculty of Military Health Sciences, University of Defense, USA
Trebesska 1575, HradecKralove, Czech Republic
ANDRES M. LUGO, MD, MPH, FACMT 5855 Evergreen Ln,
KIRAN KALIA, PhD (Biochemistry) Professor in Biochemistry, Shoreview, MN55126, USA
Laboratory of Biochemistry, BRD School of Biosciences, Sardar
GALINA F. MAKHAEVA, PhD Head of Laboratory of Molec-
Patel Maidan, Vadtal Road, Satellite Campus, Post Box No. 39,
ular Toxicology, Institute of Physiologically Active Compounds
SardarPatelUniversity,VallabhVidyanagar,388120,Gujarat,India
RussianAcademyofSciences,1SevernyProezd,Chernogolovka,
JIRI KASSA Department of Toxicology, Faculty of Military Moscow Region142432, Russia
Health Sciences, University of Defense, Trebesska 1575, Hradec
TOMAZMARS,MD,PhD Assistant Professor of Pathophysio-
Kralove, Czech Republic
logy,Laboratory for Molecular Neurobiology, InstituteofPatho-
ALEXANDRE M. KATOS Medical Illustrator, Neurobehavioral physiology,FacultyofMedicine,UniversityofLjubljana,Zaloska
Toxicology Branch, Analytical Toxicology Division, Oak Ridge 4, 1000Ljubljana,Slovenia
Associated Universities, US Army Medical Research Institute of
MARIA ROSA MART´INEZ-LARRAN˜AGA Departamento de
Chemical Defense, 3100 Ricketts Point Road, APG-EA, MD
Toxicolog´ıayFarmacolog´ıa,FacultaddeVeterinaria,Universidad
21201-5400, USA
Complutense deMadrid, 28040,Spain
KAI KEHE, MD Bundeswehr Institute of Pharmacology and
PATRICKMASSON CentredeRecherchesduServicedeSante´
Toxicology, Neuherbergstr. 11,80937Munich, Germany
des Arme´es, Unite´ d’Enzymologie, BP87, 38702 La Tronche
R. J. KERN Department of Biochemistry and Biophysics and Cedex, France
Faculty of Toxicology, Texas AgriLife Research, Texas A&M
SHIGEKIMASUNAGA,PhD, GraduateSchoolofEnvironment
University, College Station, TX77843-2128, USA
and Information Science, EIS Building No. 4, Room 107,
NATALIAKHLEBNIKOVA,PhD ResearchInstituteofHygiene, Yokohama National University, 79-7 Tokiwadai Hodogaya-ku,
Occupational Pathology and Human Ecology, Bldg 93, p.o.Kuz- Yokohama-240-8501, Japan
molovsky, Saint-Petersburg, 188663,Russia
LINDA A. McCAULEY, PhD, FAAN Nightingale Professor
JOSEPH KING US Army Environmental Command, ATTN: of Nursing, Associate Dean for Research, School of Nursing,
IMAE-CDW, Bldg E-4480, Aberdeen Proving Ground, MD 420 Guardian Dr., University of Pennsylvania, Philadelphia,
21010-5401, USA PA, USA
MARKKRASNA,MD MedicalDirectorandThoracicSurgeon, EDWARD MEEK, MS Laboratory Manager, Center for Envi-
The Cancer Institute at St Joseph Medical Center, 7501 Osler ronmental Health Sciences, College of Veterinary Medicine, 240
Drive, Towson,MD 21204,USA Wise Center Drive, Mississippi State,MS39762,USA
xiv List of Contributors
ELAINE MERRILL Henry M. Jackson Foundation for the Institute of Chemical Defense, 3100 Ricketts Point Road, APG-
AdvancementofMilitaryMedicine,AFRL/RHPBBldg837,2729 EA,MD 21201-5400,USA
RStreet, Wright-Patterson AFB, OH45433-5707,USA
CAREY POPE, PhD Department of Physiological Sciences,
DEJAN MILATOVIC, PhD Vanderbilt University School of Center for Veterinary Health Sciences, Oklahoma State Univer-
Medicine, Department of Pediatrics/Pediatric Toxicology, sity, USA
Department of CancerBiology, Nashville, TN,USA
ANDREY RADILOV, MD, PhD, Dr Sci (Medicine) Research
IGORMINDUKSHEV,PhD,DrSci(Physiology) I.M.Sechenov Institute of Hygiene, Occupational Pathology and Human
Institute of Evolutionary Physiology and Biochemistry, Russian Ecology, Bldg 93, p.o.Kuzmolovsky, Saint-Petersburg, 188663,
Academy of Sciences, ul.Moriza Toreza 44, Saint-Petersburg, Russia
194223, Russia
SHASHI K. RAMAIAH, DVM, PhD, DACVP, DABT Senior
KATARINA MIS, PhD Research Associate, Laboratory for PrincipalScientist,BiomarkerandClinicalPathologyLead,Pfizer:
MolecularNeurobiology,InstituteofPathophysiology,Facultyof DrugSafetyResearchandDevelopment,StLouis,MO63110,USA
Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana,
ARAMANDLA RAMESH Department of Cancer Biology,
Slovenia
Meharry Medical College,Nashville, TN,USA
TSAFRIR S. MOR CenterforInfectiousDiseasesandVaccinol-
ARUNABHARAY, MD,PhD, FAMS Professor, Department of
ogyattheBiodesignInstituteandSchoolofLifeSciences,POBox
Pharmacology, Vallabhbhai Patel Chest Institute, University of
874501,ArizonaStateUniversity,Tempe,AZ85287-4501,USA
Delhi, Delhi-110007, India
SHREE MULAY Faculty of Medicine, Memorial University,
VLADIMIR REMBOVSKIY, MD, PhD, Dr Sci (Medicine)
St Johns,NL,USA
Professor,ResearchInstituteofHygiene,OccupationalPathology
MICHAELJ.MURPHY,JD,DVM,PhD,DABT,DABVT Univer- andHumanEcology,Bldg93,p.o.Kuzmolovsky,Saint-Petersburg,
sity of Minnesota, Toxicology Graduate Program, Minnesota 188663,Russia
VeterinaryDiagnosticLab,1333GortnerAvenue,SaintPaul,MN
RUDYJ.RICHARDSON,ScD,DABT ProfessorofToxicology,
55108,USA
University of Michigan, 1420 Washington Heights, Ann Arbor,
KAMILMUSILEK CenterofAdvancedStudiesandDepartment MI 48109-2029,USA
ofToxicology,FacultyofMilitaryHealthSciences,Universityof
PETER J. ROBINSON The Henry M. Jackson Foundation,
Defence, Trebesska 1575, 500 02 Hradec Kralove, Czech
Applied Biotechnology Branch, Air Force Research Laboratory,
Republic
Bldg837,2729RStreet,WrightPattersonAFB,OH45433,USA
TROND MYHRER, PhD Principal Researcher, Norwegian DANIEL ROCHU, Sci D Centre de Recherches du Service de
Defence Research Establishment, Protection Division, Insti- Sante´ desArme´es,La Tronche, France
tuttveien 20,PO Box25,NO-2027Kjeller, Norway
CHRIS RUARK Henry M. Jackson Foundation for the
TETSU OKUMURA, MD, PhD Department of Crisis Manage- AdvancementofMilitaryMedicine,AFRL/RHPBBldg837,2729
ment MedicineonCBRNE Threats,Saga University, Nabeshima R Street,Wright-Patterson AFB, OH45433-5707,USA
5-1-1,Saga,Saga, Japan
IGOR RYBALCHENKO, PhD, Dr Sci (Chemistry) Professor,
DENNISOPRESKO Toxicology and Hazard Assessment, Envi- Research Council onAnalytical Chemistry, Russian Academy of
ronmental Sciences Division, Oak Ridge National Laboratory, Sciences, Leninskiy Prospect 31,Moscow, 119991,Russia
1060CommerceParkDrive,OakRidge,TN37830-6480,USA
TETSUO SATOH, PhD, FATS Professor Emeritus, Chiba
JIRI PATOCKA, DSc, Professor, Department of Radiology and University, Director, HAB Research Institute, Cornea Center,
Toxicology, Faculty of Health and Social Studies, University of Ichikawa General Hospital,5-11-13 Sugano,Ichikawa 272-8513,
South Bohemia Ceske Budejovice,Czech Republic Chiba, Japan
JOHN A. PICKRELL, DVM, PhD, DABT Comparative Toxi- ELENA SAVELIEVA, PhD Research Institute of Hygiene,
cology Laboratories, Diagnostic Medicine/Pathobiology, College Occupational Pathology and Human Ecology, Bldg 93, p.o.Kuz-
of Veterinary Medicine, Kansas State University, 1800 Denison molovsky, Saint-Petersburg, 188663, Russia
Avenue, Manhattan, KS66506-5606, USA
GEETU SAXENA School of Medicine and Public Health,
SERGEJ PIRKMAJER, MD Assistant Professor of Pathophysi- Department of Medicine, University of Wisconsin, Madison, WI
ology,Laboratory forMolecular Neurobiology, Institute ofPath- 53792, USA
ophysiology, Faculty of Medicine, University of Ljubljana, LAWRENCE M. SCHOPFER Eppley Institute, University of
Zaloska 4, 1000Ljubljana,Slovenia Nebraska Medical Center, Omaha,NE68198, USA
EKATERINA PODOLSKAYA, PhD Institute of Analytical MANU SEBASTIAN, DVM, MS, PhD, Dipl. ACVP AND
Engineering, Russian Academy of Sciences, Rizhsky prosp. 26, ABT Chief of Comparative Pathology/Asstistant Professor of
Saint-Petersburg, 190103, Russia Pathology, College of Physicians and Surgeons, Columbia
University, New York, NY, USA
MELISSA J. POOLE Senior Laboratory Technician, Neuro-
behavioral Toxicology Branch, Analytical Toxicology Division, YASUO SETO, PhD National Research Institute of Police
Oak Ridge Associated Universities, US Army Medical Research Science, 6-3-1Kashiwanoha, Kashiwa City277-0882, Japan
Listof Contributors xv
MICHAELP.SHAKARJIAN AssistantProfessor,Departmentof ANNETTA WATSON, PhD Toxicology and Hazard Assess-
Medicine,UMDNJ-RobertWoodJohnsonMedicalSchool,Room ment, Environmental Sciences Division, Oak Ridge National
C-B08, 675HoesLane,Piscataway, NJ08854, USA Laboratory, 1060Commerce Park Drive, Oak Ridge, TN 37830-
6480, USA
MANOJ SHARMA Defence Research and DevelopmentEstab-
lishment,Gwalior – 474002,India J. R. WILD, PhD Department of Biochemistry and Biophysics
andFacultyofToxicology,TexasAgriLifeResearch,TexasA&M
ALEXEY SHPAK, PhD M.V. Lomonosov Moscow State
University, College Station, TX 77843-2128,USA
University, Leninskie Gory, Moscow,119899, Russia
PATRICK T. WILLIAMS, MS Research Biologist, Neuro-
HERMONA SOREQ, PhD The Department of Biological
behavioral Toxicology, US Army Medical Research Institute of
Chemistry, The Hebrew University of Jerusalem, Jerusalem
Chemical Defense, 3100 Ricketts Point Road, APG-EA, MD
91904, Israel
21201-5400, USA
SIGRUN HANNE STERRI Protection Division, Norwegian
TINAWISMER,DVM,DABVT,DABT ASPCAAnimalPoison
Defence Research Establishment,Kjeller, Norway
Control Center, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802,
KOUICHIRO SUZUKI Department of Acute Medicine, Kawa- USA
sakiMedical University, Japan
RANDALLL.WOLTJER,MD,PhD OregonHealthandScience
KENJI TAKI Department of Emergency Medicine, Saga University, 3181 SW Sam Jackson Park Road, Mail Code L113,
University, Japan Department ofPathology, Portland,OR 97239,USA
SYLVIA S. TALMAGE, PhD Summitec Corporation, Knoxville, R. MARKWORDEN,PhD ProfessorofChemicalEngineering
TN 37922,USA and Materials Science, Michigan State University, 2527 Engi-
neering Building,East Lansing,MI 48824-1226,USA
HORST THIERMANN, PD, MD Bundeswehr Institute of
PharmacologyandToxicology,Neuherbergstr.11,80937Munich, FRANZ WOREK, PD, MD Bundeswehr Institute of Pharma-
Germany cology and Toxicology, Neuherbergstr. 11, 80937 Munich,
Germany
LARRYJ.THOMPSON,DVM,PhD,DABVT SeniorResearch
Scientist, Nestle´ Purina PetCare, 1 Checkerboard Square, St LINNZI WRIGHT Department of Physiological Sciences,
Louis,MO63164, USA Center for Veterinary Health Sciences, Oklahoma State Univer-
sity, USA
E. TIFFANY-CASTIGLIONI, PhD Department of Integrated
BiosciencesandFacultyofToxicology,TexasAgriLifeResearch, DAVIDT.YEUNG,PhD ProgramSpecialist,NationalInstitutes
Texas A&M University, CollegeStation, TX 77843-2128,USA of Health, NINDS, 6001 Executive Blvd, NSC, Room 2195A,
LUIS G. VALERIO, Jr., PhD Office of Pharmaceutical Science, Bethesda, MD20892, USA
CenterforDrugEvaluationandResearch,UnitedStatesFoodand ROBERT A. YOUNG Toxicology and Hazard Assessment,
DrugAdministration, SilverSpring,MD 20993-0002,USA EnvironmentalSciencesDivision,OakRidgeNationalLaboratory,
1060CommerceParkDrive,OakRidge,TN37830-6480,USA
M. J. VAN DER SCHANS, PhD TNO Defense Security and
Safety, POBox 45,2280AARijswijk,The Netherlands SHIRLEY ZAFRA-STONE, BS InterHealth Research Center,
5451Industrial Way,Benicia, CA,USA
DAYA R. VARMA, PhD Departments of Pharmacology and
Therapeutics, McGillUniversity, Montreal, Quebec,Canada SNJEZANAZAJA-MILATOVIC VanderbiltUniversitySchoolof
R. VIJAYARAGHAVAN Director, Defence Research and Medicine, Department of Pediatrics/Pediatric Toxicology,
Development Establishment,Gwalior – 474002,India Department ofCancerBiology, Nashville, TN,USA
MAXIM VINOKUROV, PhD, Dr Sci (Biophysics) Institute of VALERIY ZINCHENKO, PhD, Dr Sci (Biophysics) Professor,
Cell Biophysics, Russian Academy of Sciences, ul.Institutskaya Institute of Cell Biophysics, Russian Academy of Sciences,
#3, Pushchino,Russia ul.Institutskaya #3,Pushchino,Russia
M. E. WALES Department of Biochemistry and Biophysics, CSABA K. ZOLTANI, PhD Recently (April 2008) retired from
Texas AgriLife Research, Texas A&M University, College the US Army Research Laboratory, Aberdeen Proving Ground,
Station, TX 77843-2128,USA MD 21005,USA
Foreword
TETSUOSATOH,PHD,FATS
Ahighlytoxicchemicalintendedtoharm,kill,incapacitate, biosensors, biomarkers, prophylacticand therapeutic coun-
or control adversaries in warfare is called a chemical termeasures, and decontamination and detoxification
warfare agent (CWA). Throughout the world, some 70 procedures. In addition, the book serves as a significant
differentchemicalshavebeendevelopedandproduced,and source of information for nuclear and biological warfare
many of them have been stockpiled as CWAs or chemical agents. Therefore, this book appears to be an extremely
weaponsofmassdestructions(CWMD)duringthe20thand useful reference source for academicians and regulatory
21stcenturies.Theuseofbiotoxins(botulinumtoxin,ricin, authoritiesforriskandsafetyassessment,andmanagement
saxitoxin, anthrax, etc.) is also sometimes referred to as of chemical terrorism. The information provided in this
chemical warfare. book will draw immense attention from federal and state
AlthoughtheuseofCWAsdatesbacktothe5thcentury agencies, as well aspoliticaldecision makers.
BC, modernCWAs were notused atfullscale until World Theeditor,contributors,andpublisherfacedtremendous
WarI.Sincethen,avarietyofCWAshavebeendeveloped challenges in order to cover comprehensively all possible
and deployed in many wars, conflicts, terrorist attacks, aspects of the toxicology of CWAs. Presently, there are at
hostage crises, and riots. These chemicals came into the least two dozen chemicals that can be used as CWAs.
limelightparticularlyduetoGulfWarSyndrome(aftermath Organophosphate (OP) nerve agents and mustards have
ofGulfWarI,1991)andtheTokyoSubwayterroristattacks beenmostfrequentlyusedandaremostlikelytobeusedin
in 1994 and 1995. In the present world situation, the the future by terrorists and dictators throughout the world,
intentionaluseofhighlytoxicchemicalsasCWAs/CWMD because of their easy access and delivery systems. As
isagrowingconcernforgovernmentofficialsandcivilians aresult,thesechemicalshavebeenextensivelystudied,and
alike in developing as well as industrialized countries. books, monographs, reviews, and papers are widely pub-
The terrorist attacks in New York City on September 11, lished.Recently,AcademicPress/Elsevierpublishedamost
2001 led to an increased awareness of protecting national comprehensive book entitled Toxicology of Organophos-
monuments, landmarks, federal and state buildings, and phate and Carbamate Compounds, and Handbook of Toxi-
workplaces, in addition to civilians, as possible terrorist cologyofChemicalWarfareAgentsappearstobeuniquein
targets. providing a thorough assessment of all possible aspects of
Performing a comprehensive analysis of the inadequate toxicology, risk assessment, and remedial measures of
database on chemical warfare agents is often a highly CWAs inhumans,animals,and wildlife.
demanding task for toxicologists, risk assessors, regulatory Thecontributorsofthisbookfromaroundtheglobe are
agencies, and policy and decision makers at both state and leading scientists and internationally recognized for their
federal levels. Due to the lack of adequate control, legisla- expertiseinparticularareasoftoxicologyofCWAs/CWMD
tion, regulations, and knowledge, the term ‘‘chemical andcountermeasures.Thebookisdividedintoninesections
warfare’’ is often misunderstood or misused. In the recent that deal with different aspects of CWAs. Section I deals
past, in order to protect people and educate them about extensively with the historical perspective, epidemiology
terrorist attacks, a variety of Standards and Exposure and global impact of CWAs. Section II covers the broad
Guidelines have been made available, and on January 23, array of chemical agents that can be weaponized and
2008,theU.S.DepartmentofLaborpublished‘‘Safetyand deployed as CWMD. In this section, toxicity profile,
Health Topics,Chemical Terrorism’’. mechanism of action, risk assessment, and prophylactic/
HandbookofToxicologyofChemicalWarfareAgentsis therapeutic measures of the individual chemicals are
the first book on chemical warfare agents that provides described in an in-depth manner. Section III provides an
a plethora of knowledge on the historical perspective, exhaustive coverage of target organ toxicity, which is
epidemiology, detailed toxicology profile of CWAs/ indeed a novel aspect of this book. Several chapters on
CWMD, target organ toxicity, analytical methodologies, special topics about OP nerve agents, including molecular/
xvii
xviii Foreword
cellular mechanisms and neuropathological modulations, noveloximes.ProphylaxisandtherapeuticsforotherCWAs
arediscussedinsectionIV.SectionVdescribestherisksto are discussed in section II dealing with individual CWAs.
animals and wildlife associated with CWAs and chemicals The final section (IX) deals with information on decon-
ofterrorcontaminatingfeedandwaterreservoirs,whichcan tamination anddetoxification ofCWAs.
have aserious impact on human andanimal healthandthe In essence, this book is a landmark publication in the
environment. Section VI deals with the metabolism, tox- field of toxicology of CWAs/CWMD, as it provides
icokinetics and physiologically based pharmacokinetics of comprehensivecoverageofthesechemicalsandemphasizes
CWAs.Anovelsection(VII)isintroducedwithsixchapters current and novel issues that have not previously been
that provide discussion of analytical methodologies, addressed. It is hoped that this book will aid not only
biosensors,andbiomarkersofCWAs.Thesetopicswillaid academiciansbutlaypersonsincommunitypreparednessat
researchers in determining the extent of human/animal local, state, and federal levels to protect civilians, military
exposure, risk/safety assessment of CWAs, and manage- personnel, animals, wildlife, and the environment from
ment of poisoning. Section VIII covers extensively the chemical attacks by terrorists, dictators, and other adver-
unique approaches and strategies involved in prophylactic saries.Thisbookwillbeaninvaluablesourceofinformation
and therapeutic management and countermeasures. Many for homeland security, the Department of Defense, the
novel topics are included in this section, such as medical DepartmentofVeteranAffairs,theDepartmentofDefense
management of not only military personnel but civilians Research Establishment, diagnostic labs, poison control
(moreimportantlythepediatricpopulation),physiologically centers, federal, state and local authorities, forensic scien-
based pharmacokinetic modeling in countermeasures, tists, pharmacologists, toxicologists, chemists, biologists,
catalytic and non-catalytic bioscavenging enzymes, and environmentalists, teachers, students,and libraries.