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

Medical Diagnosticsdifficult to interpret the results of potential incidents.Therefore, in addition to assessing performance in animalmodels and archived human samples, it is essentialto determine potential background levels and incidenceof markers in nonexposed human populations.It should be stressed that, for the purpose of exposureverification, results from laboratory testing must beconsidered along with other information, such as thepresentation of symptoms consistent with the agent inquestion and results from environmental testing.In the late 1980s the US Army Medical ResearchInstitute of Chemical Defense was tasked by the Departmentof Defense to develop methods that couldconfirm potential chemical warfare agent exposure.The US Army Medical Research Institute of ChemicalDefense had previously published procedures forverifying exposure to nerve agents and sulfur mustard.These methods primarily focused on GC-MS analysisof hydrolysis products excreted in the urine followingexposure to chemical warfare agents. Subsequently, themethods using urine or blood samples were compiledas part of Technical Bulletin Medical 296, titled “AssayTechniques for Detection of Exposure to Sulfur Mustard,Cholinesterase Inhibitors, Sarin, Soman, GF, andCyanide.” 2 The publication was intended to provideclinicians with laboratory tests to detect exposure tochemical warfare agents.In the mid 1990s, after the publication of TechnicalBulletin Medical 296, the military adapted some of thelaboratory analytical methods for field-forward use.The concept was demonstrated by the US Army 520thTheater Army Medical Laboratory, which used theTest-Mate OP Kit (EQM Research Inc, Cincinnati, OH)for acetylcholinesterase (AChE) assay and a fly-awayGC-MS system. The lengthy preparation of GC and MSsamples for analysis in a field environment was oneof the reasons that alternative methods of analysis forchemical warfare agents were later examined.Preexposure treatments or tests to monitor potentialchemical agent exposure may be warranted for militarypersonnel and first responders who must enter or operatein chemically contaminated environments. However,laboratory testing may not be as useful for largecivilian populations unless there is a clear impendingchemical threat. At the same time, determining thehealth effects of chemical exposure is complex becauseit can affect the nervous system, respiratory tract, skin,eyes, and mucous membranes, as well as the gastrointestinal,cardiovascular, endocrine, and reproductivesystems. Individual susceptibility, preexisting medicalconditions, and age may also contribute to the severityof a chemically related illness. Chronic exposures, evenat low concentrations, are another concern. In additionto development of diagnostic technologies, strategiesto detect chemical agent exposure have become apublic health issue.The transition of laboratory-based analytical techniquesto a far-forward field setting can generatevaluable information for military or civilian clinicians.In this transition, problems such as data analysis,interpreting complex spectra, and instrument troubleshootingand repair may need addressing. As analyticalmethods are developed, refined, and sent fartherfrom the laboratory, advanced telecommunication willbe needed to provide a direct link between researchscientists and field operators; telecommunication willbecome critical to confirming patient exposure andtracking patient recovery and treatment.This chapter provides a basic outline and referencesfor state-of-the-art analytical methods presentlydescribed in the literature. Methods of verificationfor exposure to nerve agents, vesicants, pulmonarytoxicants, metabolic poisons, incapacitating agents,and riot control agents will be reviewed. Biologicalsample collection, handling, storage, shipping, andsubmission will be explained.NERVE AGENTSBackgroundThe first organophosphorus (OP) nerve agent,tabun (NATO designation: GA) was developedshortly before and during World War II by Germanchemist Gerhard Schrader at IG Farbenindustrie inan attempt to develop a commercial insecticide. 3,4,5Shortly thereafter, sarin was synthesized. Both areextremely toxic. The German government realizedthe compounds had potential as chemical warfareagents and began producing them and incorporatingthem into munitions. Subsequently, soman (NATOdesignation: GD) was synthesized, but only smallamounts were produced by the end of the war. 4 Fiveof the OP compounds are generally regarded as nerveagents: tabun, sarin, soman, cyclosarin (NATO designation:GF), and Russian VX. 4 These compoundsdemonstrated extreme toxicity, which was attributedto long-lasting binding and inhibition of the enzymeAChE. As a result, the compounds were referred toas “irreversible” inhibitors. Related, but less toxiccompounds (ie, “reversible” inhibitors), are becomingwidely used therapeutically; for example, in the treatmentof Alzheimer’s disease. The relative descriptionas reversible or irreversible refers to the length of thebinding to the enzyme (Figure 22-1).693