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

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Cyanide PoisoningToxicityAlthough generally considered to be very toxicsubstances when compared with other lethal chemicalwarfare agents, cyanides are among the least toxic.The LCt 50for HCN is generally stated to be 2,500 to5,000 mg•min/m 3 ; for cyanogen chloride, about 11,000mg•min/m 3 . (Comparable values for the nerve agentsare 10–200 mg•min/m 3 ; for sulfur mustard, 1,500mg•min/m 3 ; and for phosgene, 3,000 mg•min/m 3 .) 65The estimated intravenous dose of HCN for humansthat is lethal to 50% of the exposed population (LD 50)is approximately 1.0 mg/kg, and the estimated LD 50for liquid on the skin is about 100 mg/kg.DETECTION OF CYANIDE AND CYANIDE METABOLITESThe determination of cyanide, or its metabolitesthiocyanate and ATCA, in biological fluids is oftenneeded for forensics, clinical, research, or veterinarypurposes. Although the detection of cyanide andcyanide compounds in other matrices is important toindustrial, environmental, and research applications,it is not discussed in this chapter. This chapter willbriefly discuss the available techniques and identifyproblems in cyanide analysis. Analytical methods fordirect determination of cyanide and cyanide metabolitesin biological samples have been reviewed. 15,54,66,67Methods of analysis include spectrochemical absorptionor luminescence methods, 21,35,68–104 electrochemicalmethods, 68–76 capillary electrophoresis, 77,78 and gas 105–126or liquid chromatography techniques 127–149 coupledto a variety of detection techniques. The number ofliterature references (more than 200) that examinethe detection of cyanide and cyanide metabolites inbiological fluids can add to the difficulty in choosinga method. In addition, the numerous uncertainties anddiscrepancies in the literature have made comparisonand selection of a method complicated for the novice.Obviously the first decision will be whether to choosecyanide, one of its metabolites, or both as the substanceor substances to look for. Factors that influence thischoice are cellular absorption and detoxification kinetics,sampling and analysis time, sample storage timeand conditions, sample matrix, interferences, detectionlimits, available equipment and expertise, and budgetallowances.The analytical determination of cyanide and/or cyanidemetabolites before antidotal treatment providesa more accurate assessment of the severity of poisoningand insight into antidote dose levels (especiallybecause high doses of antidotes can also be toxic). 19,79,80However, no available method is simple, accurate, andfast enough to justify waiting for test results beforeantidotal treatment is administered (ie, cyanide can killfaster than the analysis can be performed). Measurementof cyanide and its metabolites may have diagnosticor therapeutic value when sublethal; minimallyor moderately symptomatic exposure is part of thedifferential diagnosis. In addition, biological samplesshould be assessed for confirmation or refutation of aputative diagnosis of cyanide intoxication.Blood has been the biological sample of choicewhen determining cyanide concentrations. However,cyanide is rapidly removed from blood by detoxificationprocesses, binding to proteins and enzymes thatcontain metal centers or heme moieties, or sequesteringin other favorable cellular entities. 21,40,67,81–92 Cyanidecharacteristics 93,94 suggest that a biological sampleshould be collected quickly, and analysis should beperformed as soon as possible. If analysis of cyanidecannot be performed quickly, then the sampling andstorage of biological samples for later testing shouldconsider the following:• Cyanide resides mainly in erythrocytesrather than plasma. Cyanide in blood primarilyresides in erythrocytes (red bloodcells) 40,82,89–92,95 by binding to methemoglobin,forming cyanomethemoglobin, but may alsobe present in plasma, especially if cyanideconcentrations exceed erythrocyte concentrations.40,82,89 Test results are improved by workingwith whole blood that is not coagulated.Heparinized vials should be used in the collectionof the blood sample for determinationof cyanide concentration. Containers thatcontain anticoagulants such as heparin andethylenediaminetetraacetate (EDTA) helpprevent clotting and also ensure efficientharvesting of plasma after the blood has beencentrifuged. Lundquist et al demonstratedthat the cyanide binding capacity of erythrocytesdue to methemoglobin increased from89,000 nM to 517,000 nM upon addition ofsodium nitrite. 82• Cyanide may evaporate because of HCNvolatility at the physiological pH, and cyanidenucleophilic action should be reduced.The next considerations should be reducingthe evaporation and loss of cyanide frombiological samples and preventing nucleophilicreactions. Using tightly sealed vials,377
Medical Aspects of Chemical WarfareTABLE 11-2Analytical methods to identify cyanide and its metabolites in biological fluids*Detection Limit †Analyte Matrix Studied Analytical Method nM ng/mL Estimated Time StudyGas ChromatographyHCN Human blood (whole) Headspace analysis GC-MS 300 8 ~20 1(internal standard: K 13 C 15 N)HCN Human blood (whole) Headspace analysis GC with NPD (also 519 14 ~ 17 min 2used SPME); calibration curveHCN Human blood (whole) Headspace analysis GC with NPD and 74 2 ~ 35 min 3cryogenic oven (internal standard:propionitrile)HCN Human blood (whole) HPLC-MS after derivatization 185 5 ~ 45 min 4(internal standard: K 13 C 15 N)HCN Cow serum, rumen, GCMS after derivatization (internal 700 18 ~ 55 min 5liverstandard: bromocyclohexane in ethylacetate)HCN, Human blood (whole) For HCN: GC-EC after derivatization; 10,000 270 ~55 min 6SCN − for SCN − : GC-EC after derivatization; 3,000 174(internal standard: 1,3,5 tribromobenzenein ethyl acetate)ATCA Blood plasma, urine GC-MS; (internal standard: ATCA-d 2) 171.2 25 > 1 h 7ElectrochemicalHCN Human blood (whole) Voltammetry with Ag RDE following 1,000 27 > 50 min 8trapping of HCN gasSCN − Human urine and Thiocyanate selective polymeric 48 2.8 15 or 120 s for 9saliva membrane electrode (electrode conditionedconditioning requires 24 h; pH rangeelectrode5–10)Liquid ChromatographyHCN Human blood (whole) HPLC with fluorometric detection after 74 2 > 2 h 10derivatizationHCN, Human blood (whole) For HCN: IC with F detection after 3.8 0.10 ~ 45 min 11SCN − derivatization; for SCN − : IC with UV 86 5detectionSCN − Human urine Ion interaction LC with UV detection 1,720 100 ~ 10 min 12SCN − Human urine IC with electrochemical detection 500 29 ~ 15 min 13SCN − Human blood (whole) HPLC with fluorometric detection after 0.165 0.0096 > 1 h 14derivatizationSCN − Human plasma and IC with spectrophotometric detection 930 54 ~ 25 min 15urinefollowing chlorinationATCA Human urine HPLC with fluorometric detection after 300 44 > 3 h 16derivatization(Table 11-2 continues)378
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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 349 and 350: Medical Aspects of Chemical Warfare
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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