Medical Aspects of Chemical Warfare (2008) - The Black Vault
Medical Aspects of Chemical Warfare (2008) - The Black Vault Medical Aspects of Chemical Warfare (2008) - The Black Vault
Medical DiagnosticsStorageUpon arrival, the receiving laboratory should maintaina proper chain of custody. If the samples are notprocessed immediately, they should be stored as soonas possible after arriving at the receiving laboratory.Storing samples either before or after they are shippedshould be in accordance with conditions dictated bythe sample type. Blood should be stored refrigeratedat 4°C. Plasma or serum should be stored frozen at–70°C. RBCs can be stored refrigerated at 4°C or frozenat –70°C; freezing is preferred for long-term storage.Avoid repeated cycles that move samples from frozento thawed or refrigerated to room temperature.summaryThe general class of agents involved in severe intoxication(ie, OP nerve agents, vesicants, etc) can often berecognized by symptom presentation. However, testingis necessary to identify the specific agent involved.In cases where poisoning is suspected at low levels andsymptoms do not clearly indicate intoxication with aspecific chemical warfare agent, testing can provideadditional information to help consider or rule out anexposure. In general, confirmatory analyses shouldnot be initiated in the absence of other informationthat suggests a potential exposure has taken place;other evidence, such as patient signs or symptoms,environmental monitoring and testing, and threat intelligenceinformation should also be considered. Thisinformation should be used to guide decisions aboutwhat agent or class of agents should be the focus oftesting and it should ultimately be used in conjunctionwith test results to determine whether or not anexposure has occurred.Analytical methods for verifying chemical agent exposuredo not employ instrumentation that is routinelyused for standard clinical testing, such as automatedclinical analyzers. With the exception of cholinesteraseanalysis, instrumentation typically involves MSsystems with either GC or LC techniques to separatethe analyte from other matrix components. Althoughthe methods are desirable because they afford a highlevel of confidence for identifying the analyte, theyare time and labor intensive. Consequently the turnaroundtime for analyses is greater than that expectedfor standard clinical tests.Chemical warfare agents have been used againstboth military and civilian populations. In many ofthese cases, healthcare providers have learned thatit is critical to rapidly identify exposed personnelto facilitate appropriate medical treatment and support.Incidents involving large numbers of personnelhave shown that is also important to determine thosenot exposed to avoid unnecessary psychologicalstress and overburdening the medical system. Inaddition to medical issues, the political and legalramifications of chemical agent use by rogue nationsor terrorist organizations can be devastating.Therefore, it is important that accurate and sensitiveanalytical techniques be employed and appropriatelyinterpreted.REFERENCES1. Matsuda Y, Nagao M, Takatori T, et al. Detection of the sarin hydrolysis product in formalin-fixed brain tissues ofvictims of the Tokyo subway terrorist attack. Toxicol Appl Pharmacol. 1998;150:310–320.2. Department of the US Army. Assay Techniques for Detection of Exposure to Sulfur Mustard, Cholinesterase Inhibitors, Sarin,Soman, GF, and Cyanide. Washington, DC: DA; 1996. Technical Bulletin Medical 296.3. Taylor P. Anticholinesterase agents. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman and Gilman’s the PharmacologicalBasis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006:201–216.4. Sidell FR. Nerve agents. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects of Chemical and Biological Warfare. In:Zajtchuk R, Bellamy RF, eds. The Textbooks of Military Medicine. Part I. Washington, DC: Borden Institute; 1997:129–179.5. Harris R, Paxman J. A Higher Form of Killing: the Secret Story of Chemical and Biological Warfare. New York, NY: Hill andWang; 1982: 53.6. Degenhardt CE, Pleijsier K, van der Schans MJ, et al. Improvements of the fluoride reactivation method for the verificationof nerve agent exposure. J Anal Toxicol. 2004;28:364–371.741
Medical Aspects of Chemical Warfare7. Noort D, Benschop HP, Black RM. Biomonitoring of exposure to chemical warfare agents: a review. Tox Appl Pharmacol.2002;184:116–126.8. Benschop HP, De Jong LP. Toxicokinetics of soman: species variation and stereospecificity in elimination pathways.Neurosci Biobehav Rev. 1991;15:73–77.9. Benschop HP, de Jong LP. Toxicokinetics of nerve agents. In: Somani SM, Romano JA, eds. Chemical Warfare Agents:Toxicity at Low Levels. Boca Raton, Fla: CRC Press; 2000:25–81. Chapter 2.10. Van der Schans MJ, Lander BJ, van der Wiel, H, Langenberg JP, Benschop HP. Toxicokinetics of the nerve agent (±) -VXin anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.Tox Appl Pharmacol. 2003;191:48–62.11. Bonierbale E, Debordes L, Coppet L. Application of capillary gas chromatography to the study of hydrolysis of thenerve agent VX in rat plasma. J Chromatogr B Biomed Sci Appl. 1997;688:255–264.12. Harris LW, Braswell LM, Fleisher JP, Cliff WJ. Metabolites of pinacolyl methylphosphonofluoridate (soman) afterenzymatic hydrolysis in vitro. Biochem Pharmacol. 1964;13:1129–1136.13. Polak RL, Cohen EM. The influence of oximes on the distribution of 32P in the body of the rat after injection of 32Psarin.Biochem Pharmacol. 1970;19:865–876.14. Reynolds ML, Little PJ, Thomas BF, Bagley RB, Martin BR. Relationship between the biodisposition of [3H]somanand its pharmacological effects in mice. Toxicol Appl Pharmacol. 1985;80:409–420.15. Little PJ, Reynolds ML, Bowman ER, Martin BR. Tissue disposition of [3H]sarin and its metabolites in mice. ToxicolAppl Pharmacol. 1986;83:412–419.16. Shih ML, Smith JR, McMonagle JD, Dolzine TW, Gresham VC. Detection of metabolites of toxic alkylmethylphosphonatesin biological samples. Biol Mass Spectrom. 1991;20:717–723.17. Shih ML, McMonagle JD, Dolzine TW, Gresham VC. Metabolite pharmacokinetics of soman, sarin, and GF in rats andbiological monitoring of exposure to toxic organophosphorus agents. J Appl Toxicol. 1994:14:195–199.18. Tsuchihashi H, Katagi M, Nishikawa M, Tatsuno M. Identification of metabolites of nerve agent VX in serum collectedfrom a victim. J Anal Toxicol. 1998;22:383–388.19. Fredriksson SA, Hammarström LG, Henriksson L, Lakso HA. Trace determination of alkyl methylphosphonic acids inenvironmental and biological samples using gas chromatography/negative-ion chemical ionization mass spectrometryand tandem mass spectrometry. J Mass Spectrom. 1995;30:1133–1143.20. Miki A, Katagi M, Tsuchihashi H, Yamashita M. Determination of alkylmethylphosphonic acids, the main metabolitesof organophosphorus nerve agents, in biofluids by gas chromatography-mass spectrometry and liquid-liquid-solidphase-transfer-catalyzedpentafluorobenzylation. J Anal Toxicol. 1999;23:86–93.21. Driskell WJ, Shih M, Needham LL, Barr DB. Quantitation of organophosphorus nerve agent metabolites in humanurine using isotope dilution gas chromatography-tandem mass spectrometry. J Anal Toxicol. 2002;26:6–10.22. Barr JR, Driskell WJ, Aston LS, Martinez RA. Quantitation of metabolites of the nerve agents sarin, soman, cyclosarin,VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry. J AnalToxicol. 2004;28:371–378.23. Minami M, Hui DM, Katsumata M, Inagaki H, Boulet CA. Method for the analysis of methylphosphonic acid metabolitesof sarin and its ethanol-substituted analogue in urine as applied to the victims of the Tokyo sarin disaster. JChromatogr B Biomed Sci Appl. 1997;695:237–244.24. Nakajima T, Sasaki K, Ozawa H, Sekjima Y, Morita H, Fukushima Y, Yanagisawa N. Urinary metabolites of sarin in apatient of the Matsumoto incident. Arch Toxicol. 1998;72:601–603.742
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<strong>Medical</strong> <strong>Aspects</strong> <strong>of</strong> <strong>Chemical</strong> <strong>Warfare</strong>7. Noort D, Benschop HP, <strong>Black</strong> RM. Biomonitoring <strong>of</strong> exposure to chemical warfare agents: a review. Tox Appl Pharmacol.2002;184:116–126.8. Benschop HP, De Jong LP. Toxicokinetics <strong>of</strong> soman: species variation and stereospecificity in elimination pathways.Neurosci Biobehav Rev. 1991;15:73–77.9. Benschop HP, de Jong LP. Toxicokinetics <strong>of</strong> nerve agents. In: Somani SM, Romano JA, eds. <strong>Chemical</strong> <strong>Warfare</strong> Agents:Toxicity at Low Levels. Boca Raton, Fla: CRC Press; 2000:25–81. Chapter 2.10. Van der Schans MJ, Lander BJ, van der Wiel, H, Langenberg JP, Benschop HP. Toxicokinetics <strong>of</strong> the nerve agent (±) -VXin anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.Tox Appl Pharmacol. 2003;191:48–62.11. Bonierbale E, Debordes L, Coppet L. Application <strong>of</strong> capillary gas chromatography to the study <strong>of</strong> hydrolysis <strong>of</strong> thenerve agent VX in rat plasma. J Chromatogr B Biomed Sci Appl. 1997;688:255–264.12. Harris LW, Braswell LM, Fleisher JP, Cliff WJ. Metabolites <strong>of</strong> pinacolyl methylphosphon<strong>of</strong>luoridate (soman) afterenzymatic hydrolysis in vitro. Biochem Pharmacol. 1964;13:1129–1136.13. Polak RL, Cohen EM. <strong>The</strong> influence <strong>of</strong> oximes on the distribution <strong>of</strong> 32P in the body <strong>of</strong> the rat after injection <strong>of</strong> 32Psarin.Biochem Pharmacol. 1970;19:865–876.14. Reynolds ML, Little PJ, Thomas BF, Bagley RB, Martin BR. Relationship between the biodisposition <strong>of</strong> [3H]somanand its pharmacological effects in mice. Toxicol Appl Pharmacol. 1985;80:409–420.15. Little PJ, Reynolds ML, Bowman ER, Martin BR. Tissue disposition <strong>of</strong> [3H]sarin and its metabolites in mice. ToxicolAppl Pharmacol. 1986;83:412–419.16. Shih ML, Smith JR, McMonagle JD, Dolzine TW, Gresham VC. Detection <strong>of</strong> metabolites <strong>of</strong> toxic alkylmethylphosphonatesin biological samples. Biol Mass Spectrom. 1991;20:717–723.17. Shih ML, McMonagle JD, Dolzine TW, Gresham VC. Metabolite pharmacokinetics <strong>of</strong> soman, sarin, and GF in rats andbiological monitoring <strong>of</strong> exposure to toxic organophosphorus agents. J Appl Toxicol. 1994:14:195–199.18. Tsuchihashi H, Katagi M, Nishikawa M, Tatsuno M. Identification <strong>of</strong> metabolites <strong>of</strong> nerve agent VX in serum collectedfrom a victim. J Anal Toxicol. 1998;22:383–388.19. Fredriksson SA, Hammarström LG, Henriksson L, Lakso HA. Trace determination <strong>of</strong> alkyl methylphosphonic acids inenvironmental and biological samples using gas chromatography/negative-ion chemical ionization mass spectrometryand tandem mass spectrometry. J Mass Spectrom. 1995;30:1133–1143.20. Miki A, Katagi M, Tsuchihashi H, Yamashita M. Determination <strong>of</strong> alkylmethylphosphonic acids, the main metabolites<strong>of</strong> organophosphorus nerve agents, in bi<strong>of</strong>luids by gas chromatography-mass spectrometry and liquid-liquid-solidphase-transfer-catalyzedpentafluorobenzylation. J Anal Toxicol. 1999;23:86–93.21. Driskell WJ, Shih M, Needham LL, Barr DB. Quantitation <strong>of</strong> organophosphorus nerve agent metabolites in humanurine using isotope dilution gas chromatography-tandem mass spectrometry. J Anal Toxicol. 2002;26:6–10.22. Barr JR, Driskell WJ, Aston LS, Martinez RA. Quantitation <strong>of</strong> metabolites <strong>of</strong> the nerve agents sarin, soman, cyclosarin,VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry. J AnalToxicol. 2004;28:371–378.23. Minami M, Hui DM, Katsumata M, Inagaki H, Boulet CA. Method for the analysis <strong>of</strong> methylphosphonic acid metabolites<strong>of</strong> sarin and its ethanol-substituted analogue in urine as applied to the victims <strong>of</strong> the Tokyo sarin disaster. JChromatogr B Biomed Sci Appl. 1997;695:237–244.24. Nakajima T, Sasaki K, Ozawa H, Sekjima Y, Morita H, Fukushima Y, Yanagisawa N. Urinary metabolites <strong>of</strong> sarin in apatient <strong>of</strong> the Matsumoto incident. Arch Toxicol. 1998;72:601–603.742
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