Medical Aspects of Chemical Warfare (2008) - The Black Vault

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Long-Term Health Effects of Chemical Threat AgentsChapter 9Long-Term Health Effects ofChemical Threat AgentsWilliam J. Smith, PhD*; Matthew G. Clark, PhD † ; Thomas B. Talbot, MD, MS ‡ ; Patricia Ann Caple, RN § ;Frederick R. Sidell, MD ¥ ; a n d Charles G. Hurst, MD INTRODUCTIONMUSTARDCarcinogenesisChronic Pulmonary DiseaseChronic Eye DiseaseScarring of Epithelial SurfacesCentral Nervous SystemMutagenesis, Teratogenesis, and Reproductive ToxicityNERVE AGENTSPolyneuropathyMuscle NecrosisIntermediate SyndromeNeuropsychiatric EffectsElectroencephalographic AbnormalitiesToxicological Studies on Nerve AgentsCYANIDEPhysiologyLong-Term Effects of an Acute InsultLong-Term ExposureTOXIC INHALATION INJURYPhosgeneMethyl IsocyanatePerfluoroisobutyleneOxides of NitrogenZinc OxideSUMMARY* Chief, Cellular and Molecular Biology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road,Aberdeen Proving Ground, Maryland 21010-5400† Major, Medical Service Corps, US Army; Chief, Neurobehavioral Toxicology Branch, Analytical Toxicology Division, US Army Medical ResearchInstitute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400‡ Major, Medical Corps, US Army; Chief of Operations Branch, Chemical Casualty Care Division, US Army Medical Research Institute of ChemicalDefense, 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400§Lieutenant Colonel, Nurse Corps, US Air Force; Chemical Casualty Care Division, US Army Medical Research Institute of Chemical Defense, 3100Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400¥Formerly, Chief, Chemical Casualty Care Office, and Director, Medical Management of Chemical Casualties Course, US Army Medical Research Instituteof Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400; Deceased Chief, Chemical Casualty Care Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen ProvingGround, Maryland 21010-5400311
Medical Aspects of Chemical WarfareINTRODUCTIONChemical warfare agents were used extensivelyin World War I (the United States had approximately70,000 chemical casualties 1 ) and have beenemployed or allegedly employed in about a dozenconflicts since then. 2 The most recent large-scaleuse of these weapons was by Iraq in its war withIran in the late 1980s. During that conflict, Iraqused nerve agents and the vesicant mustard 3 ; afterthe war it maintained stockpiles of the two agentsand the capability to manufacture them. Beforecoalition forces liberated Kuwait early in 1991during the Persian Gulf War, Iraq was expected touse these agents when attacked. No reports of theuse of chemical weapons during that conflict weremade, however, despite the vigilance of the presscorps and military medical personnel, who weretrained to report, investigate, and care for chemicalcasualties. 4,5 One US soldier developed skin blisters8 hours after exploring an underground bunker. 4His clinical findings and mass spectroscopy readings(performed by a chemical detection team) fromhis clothing and the bunker supported a diagnosisof accidental mustard exposure, which was mild.The exposure was not confirmed by later testing ofclothing samples, from which trace amounts of theagent may have dissipated.Although the acute effects of the nerve agentsand of mustard agent are well known, 6,7 the longtermeffects after a single exposure or multipleexposures are less well recognized. The nerveagents are the subject of Chapter 5, Nerve Agents,and mustard is discussed in Chapter 8, Vesicants.This chapter focuses on the long-term effects ofexposure to these agents.MUSTARDTwo well-known forms of mustard exist. Sulfurmustard (designated by the military as H or HD) wasfirst synthesized in the early 1800s, has been used inwarfare on several occasions, and is a major chemicalwarfare agent. 6 Nitrogen mustard is of more recentorigin, has not been used in warfare, and is a cancerchemotherapeutic agent. In this chapter, the word“mustard” will refer to sulfur mustard.Mustard is best known as a skin vesicant, but ina series of Iranian patients exposed to mustard, 95%had airway effects, 92% had eye injuries, and 83% hadskin lesions. 8 After absorption, mustard, an extremelypotent alkylating agent, has the potential to damageall cells and all organs. 6 Absorption and systemic distributionof a significant amount of mustard damagesthe bone marrow, where it destroys the precursor cells,resulting in pancytopenia. 6 Less commonly, clinicaleffects are seen in the gastrointestinal tract (usually asa terminal event) 9,10 and in the central nervous system(CNS), with ill-defined symptoms such as lethargyand apathy. 8,11On the skin, a Ct (the concentration [C] of agentvapor or aerosol in air, as mg/m 3 , multiplied by thetime [t] of exposure, in minutes) of 50 mg•min/m 3 ora droplet of 10 µg of mustard is adequate to producevesication. 6 (One study 12 indicates that 8 of the 10 µgevaporate and 1 µg enters the systemic circulation,leaving 1 µg to produce the skin lesion.) Eye lesionscan be produced by a Ct of 10 mg•min/m 3 . 13 Airwayinjury occurs at a Ct of 100 mg•min/m 3 or higher. 6The mode of biological activity of mustard is lesswell defined than that of the nerve agents. The initialevent is felt to be a reaction of mustard and deoxyribonucleicacid (DNA) with subsequent damage to theDNA. A series of intracellular events then occur, leadingto cellular damage accompanied by inflammationand cellular death. Cellular damage begins within 1to 2 minutes of contact of mustard to skin or mucousmembranes. 6 The onset of clinical effects followingexposure to mustard occurs hours after the exposure.6 The delay usually ranges from 2 to 24 hours, isinversely proportional to the amount of mustard, anddepends on other factors as well. No specific therapyfor mustard exposure exists. 6 Decontamination withina minute or two will prevent or diminish the lesion,and later care consists of symptomatic managementof the lesion.Studies have established that the chemical agentmustard has long-term sequelae. Both Morgensternet al 14 and Buscher 15 emphasize that chronic low-doseexposure over months to years in occupationally exposedworkers leads to chronic bronchitis, bronchialasthma, hoarseness, aphonia, and hypersensitivity tosmoke, dust, and fumes. Affected individuals typicallyshow persistent disability, with increased susceptibilityto respiratory tract infections and evidence ofbronchitis and bronchiectasis. 6,14,15 Laboratory animalstudies 16–18 have found that mustard is mutagenic andcarcinogenic, and it is reported to be carcinogenic inhumans. 19A 1993 study 19 sponsored by the Veterans Administrationand conducted by the Institute of Medicinereported that a causal relationship exists betweenmustard exposure and the following conditions:312
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The Coat of Arms1818Medical Departm
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Textbooks of Military MedicinePubli
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MEDICAL ASPECTS o fCHEMICAL WARFARE
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ContentsContributorsForeword by The
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ContributorsMICHAEL ADLER, PhDResea
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DONALD M. MAXWELL, MSResearch Chemi
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ForewordThe US military has been co
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PrefaceA significant concern for th
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PrologueThe original edition of Med
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xxii
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Medical Aspects of Chemical Warfare
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Nerve AgentsChapter 5NERVE AGENTSFR
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Nerve AgentsAbout 10,000 to 30,000
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Nerve Agentsphorofluoridate (DFP) w
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Nerve AgentsFig. 5-2. This schemati
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Nerve AgentsExhibit 5-1 continuedis
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Nerve Agentsactivity but only 15% t
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Nerve AgentsTABLE 5-3CHEMICAL, PHYS
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Nerve AgentsTABLE 5-4EFFECTS OF EXP
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Nerve Agentsaffecting the other eye
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Nerve Agentsmay cause severe rhinor
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Nerve Agentsof jerks and tremor.Cen
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Nerve Agentsand they were decreased
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Nerve Agentsnerve agent toxicity on
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Nerve Agentspatient. Decontaminatio
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Nerve AgentsFig. 5-5. The Mark I ki
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Nerve Agentsadministered intramuscu
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Nerve Agentsthat hydroxamine reacti
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Nerve AgentsOral administration may
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Nerve AgentsTABLE 5-7RECOMMENDED TH
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Nerve Agentsimpairment such as whee
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Nerve Agentssuboptimal, manner. The
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Nerve Agentsthan those who did not.
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Nerve Agentssible for binding nerve
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Nerve Agentsfor comparison was not
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Nerve AgentsTABLE 5-11EFFECTS OF PY
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Nerve Agentstivity of smooth muscle
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Nerve Agents38. Grob D, Lilienthal
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Nerve Agents77. McDonough JH, Shih
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Nerve Agents117. McLeod CG Jr, Sing
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Nerve Agents154. Tryphonas l, Veino
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Nerve Agents193. Funckes AJ. Treatm
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Nerve Agents235. Suzuki T, Morita H
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Nerve Agents274. Pellegrini JE, Bak
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Page 375 and 376: PROCESSMedical Aspects of Chemical
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Triage of Chemical CasualtiesChapte
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Triage of Chemical Casualtiesreceiv
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Triage of Chemical Casualtiesentran
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Triage of Chemical Casualtiescatego
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Triage of Chemical CasualtiesIn a f
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Triage of Chemical Casualtiesnose)
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Triage of Chemical CasualtiesWith n
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Triage of Chemical Casualties14. Sa
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Decontamination of Chemical Casualt
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• Analyze using GC-MS with methan
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Abbreviations and AcronymsAbBreviat
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Abbreviations and AcronymsPADPRP: p
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