HANDBOOK OF TOXICOLOGY OF AGENTS

Edited by

RAMESH C. GUPTA

AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • Academic Press is an imprint of Elsevier ELSEVIER Contents

List of Contributors xi 8. Mustards and Vesicants 93 Foreword xvii Robert A. Young and Cheryl Bast Tetsuo Satoh 9. : Toxicity, their Use as Chemical Warfare Agents, and Possible Remedial SECTION I Measures 109 Introduction, Historical Perspective, and Epidemiology Swaran J.S. Flora, Govinder Flora, and Geetu Saxena

1. Introduction 3 10. Psychotomimetic Agent BZ (3-Quinuclidinyl Ramesh C. Gupta Benzilate) 135 Josef Fusek, Jiri Bajgar, Jiri Kassa, Kamil Kuca, 2. Historical Perspective of Chemical Warfare and Daniel Jun Agents 7 Nathan H. Johnson, Joseph C. Larsen, and 11. Onchidal and 143 Edward Meek Arturo Anadon, Maria Rosa Martfnez-Larranaga, and Luis G. Valerio, Jr. 3. Global Impact of Chemical Warfare Agents Used Before and After 1945 17 12. Riot Control Agents 153 Jiri Bajgar, Josef Fusek, Jiri Kassa, Kami I Kuca, and Corey J. Hilmas, Melissa J. Poole, Daniel Jun Alexandre M. Katos, and Patrick T. Williams 4. The Tokyo Subway Attack: Toxicological Whole Truth 25 13. Fluoroacetate 177 Tetsu Okumura, Kenji Taki, Kouichiro Suzuki, Nikolay Goncharov, Lidia Glashkina, and Tetsuo Satoh Elena Savelieva, Valeriy Zinchenko, Sergey Kuznetsov, Maxim Vinokurov, 5. Epidemiology of Chemical Warfare Agents 33 Igor Mindukshev, Peter Avdonin, Linda A. McCauley Richard Jenkins, and Andrey Radilov

14. 199 SECTION II Jiri Patocka Agents that can be Used as Weapons of Mass Destruction 15. Superwarfarins 207 6. Organophosphate Nerve Agents 43 Michael J. Murphy and Andres M. Lugo Annetta Watson, Dennis Opresko, Robert Young, 16. Thallium 225 Veronique Hauschild, Joseph King, and Kulbir Bakshi Larry J. Thompson 7. Russian VX 69 17. Polycyclic Aromatic Hydrocarbons: Exposure Andrey Radilov, Vladimir Rembovskiy, Igor Rybalchenko, Elena Savelieva, from Emission Products and from Terrorist Ekaterina Podolskaya, Vladimir Babakov, Attacks on US Targets - Implications for Elena Ermolaeva, Sergey Dulov, Sergey Kuznetsov, Developmental Central Nervous System Igor Mindukshev, Alexey Shpak, Ilia Krasnov, Toxicity 229 Natalia Khlebnikova, Richard Jenkins, Darryl B Hood, Aramandla Ramesh, and Nikolay Goncharov and Michael Aschner VIII Contents

18. PCBs, Dioxins/ and Furans: Human Exposure 33. Behavioral Toxicity of Nerve Agents 481 and Health Effects 245 Jiri Kassa, Jiri Bajgar, Kamil Kuca, and Daniel Jun Bommanna G. Loganathan and Shigeki Masunaga 34. Cardiovascular System as a Target 19. Cyanide Toxicity and its Treatment 255 of Chemical Warfare Agents 493 R. Bhattacharya and S. J. S. Flora Csaba K. Zoltani 35. Skeletal Muscle 509 xi 20. Carbon MonChlorine 313 Sylvia S. Talmage 37. Liver Toxicity of Chemical Warfare Agents 549 Shashi K. Ramaiah and Atrayee Banerjee 23. 321 38. Renal Toxicity 561 Cheryl B. Bast 2nd Dana F. Glass Manu Sebastian

24. Other Toxic Chemicals as Potential Chemical 39. Ocular Toxicity of Sulfur Mustard 575 Warfare Agents 331 Marion K. Gordon, Robert W. Enzenauer, Jiri Bajgar, Jiri Kassa, Josef Fusek, Kami I Kuca, and Michael C. Babin and Daniel Jun 40. Immunotoxicity 595 25. and 339 Kavita Gulati and Arunabha Ray Manashi Bagchl Shirley Zafra-Stone, 41. Dermal Toxicity of Sulfur Mustard 611 Francis C. Lau, and Debasis Bagchi Donald R. Gerecke, Joshua P. Gray, Michael P. Shakarjian, and Robert P. Casillas 26. 353 Wanda M. Haschek and Val R. Beasley SECTION IV 27. of Cyan° 371 Special Topics J.F. Humbert

28. Radiation and Health Effects 381 42. Excitotoxicity, Oxidative Stress, John A. Pickrell and Neuronal Injury 633 Dejan Milatovic, Ramesh C. Gupta, 29. 393 Snjezana Zaja-Milatovic, and Michael Aschner George C-T. Jiang and Michael Aschner 43. Neuropathologic Effects of Chemical 30. Botulinum 407 Jaime Anderson, Patrick T. Williams, Warfare Agents 653 Randall L. Woltjer Alexandre M. Katos, Mark Krasna, Whitney Burrows, and Corey J. Hilmas 44. Molecular and Transcriptional Responses 31. 433 to Sarin Exposure 665 Corey J. Hilmas, Alexandre M. Katos, TV. Damodaran Patrick T. Williams, and Jaime Anderson 45. The Effects of Organophosphates in the Early Stages of Human Muscle Regeneration 683 SECTION III Tomaz Mars, Katarina Mis, Sergej Pirkmajer, Target Organ Toxicity and Zoran Grubic

46. Organophosphate Intoxication: Molecular 32. The Nervous System as a Target for Chemical Consequences, Mechanisms and Solutions 691 Warfare Agents 453 Brian C. Geyer, Tama Evron, Hermona Soreq, Linnzi Wright, Carey Pope, and Jing Liu and Tsafrir S Mor Contents IX

SECTION V 57. Biomarkers and Biosensors of Delayed Neuropathic Agents 859 Risks to Animals and Wildlife Rudy J. Richardson, R. Mark Worden, 47. Chemical Warfare Agents and Risks and Galina F. Makhaeva to Animal Health 721 58. Monitoring of Blood Cholinesterase Activity Tina Wismer in Workers Exposed to Nerve Agents 877 48. Potential Agents that Can Cause Daniel Jun, Jiri Bajgar, Kamil Kuca, and Jiri Kassa Contamination of Animal Feedstuffs and Terror 739 SECTION VIII R.W. Coppock Prophylactic, Therapeutic, and Countermeasures 49. Threats to Wildlife by Chemical Warfare Agents 747 59. Strategies to Enhance Medical R.W. Coppock Countermeasures After the Use of Chemical Warfare Agents on Civilians 889 SECTION VI David A. Jett and David T. Yeung

Toxicokinetics and Physiologically Based 60. Medical Countermeasures and Other Pharmacokinetics Therapeutic Strategies for Sulfur Mustard Toxicity 897 50. Toxicokinetics of Chemical Warfare Agents: R. Vijayaraghavan, Anshoo Gautam, Nerve Agents and Vesicants 755 and Manoj Sharma Harald John, Frank Balszuweit, Kai Kehe, Franz Worek, and Horst Thiermann 61. Medical Management of Chemical Toxicity in Pediatrics 919 51. Physiologically based Pharmacokinetic Elora Hilmas and Corey J. Hilmas Modeling of Chemical Warfare Agents 791 Jeffery M. Gearhart, Peter J. Robinson, and 62. Physiologically Based Pharmacokinetic/ Edward M. Jakubowski Phamnacodynamic Modeling of Countermeasures to Nerve Agents 951 52. of Warfare Nerve Agents 799 Elaine Merrill, Chris Ruark, Jeff Gearhart, Milan Jokanovic and Peter Robinson

SECTION VII 63. Prophylactic and Therapeutic Measures Analytical Methods, Biosensors, and Biomarkers in Poisoning 965 Trond Myhrer 53. On-Site Detection of Chemical Warfare 64. Pharmacological Prophylaxis Against Agents 813 Nerve Agent Poisoning: Experimental Yasuo Seto Studies and Practical Implications 977 54. Laboratory Analysis of Chemical Jiri Bajgar, Josef Fusek, Jiri Kassa, Kamil Kuca, Warfare Agents and Metabolites and Daniel Jun in Biomedical Samples 827 M.J. van der Schans 65. Pyridinium Oximes as Cholinesterase Reactivators in the Treatment of 55. Biosensors for the Detection of OP OP Poisoning 985 Nerve Agents 837 Dejan Milatovic and Milan Jokanovic Jun-ichi Anzai 66. Novel Oximes 997 56. Biomarkers of Exposure to Organophosphorus Kamil Kuca, Kamil Musilek, Daniel Jun, Poisons: A New Motif for Covalent Binding Jiri Bajgar, and Jiri Kassa to Tyrosine in that have No Serine 847 67. Paraoxonase (PON1) and Detoxication of Oksana Lockridge, Lawrence M. Schopfer, Nerve Agents 1023 and Patrick Masson Lucio G. Costa and Clement E. Furlong Contents

68. Role of Carboxylesterases in Therapeutic SECTION l\ Intervention of Nerve Gas Poisoning 1033 Decontamination of Chemical Warfare Agents Sigrun Hanne Sterri and Frocle Fonnum 71. Rapid Decontamination of Chemical 69. Protection of from Warfare Agents 10(>4 Organophosphates: Kinetic Insight into Richard K. Gordon and Ldw.ud D. ( Lirkson Bioscavengers 1041 R.J. Kern, M.E. Wales, E. Tiffany-Castiglioni, 72. Detoxification ot Arsenic 1083 andJ.R. Wild Kiran Kalid and Dhaval N. Joshi

70. Catalytic Bioscavengers: The Next Index 1101 Generation of Bioscavenger-Based Medical Countermeasures 1053 Patrick Masson and Daniel Rochu