Clinical Detection of Exposure to Chemical Warfare Agents

Chemical Warfare Agents: Chemistry, Pharmacology, Toxicology, and Therapeutics

Volumn , Issue , 2007, Pages 501-548

  Capacio, Benedict R ^a   Smith, J Richard ^a   Gordon, Richard K ^b   Haigh, Julian R ^b   Barr, John R ^c   Lukey, Brian J ^a  

^a US ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE   (United States)

^b WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^c CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85152838720     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/9781420046625-25     Document Type: Chapter

References (192)

1. Adams TK, Capacio BR, Smith JR, Whalley CE, Korte WD. The application of the fluoride reactivation process to the detection of sarin and soman nerve agent exposures in biological samples. Drug Chem Toxicol, 2004; 27: 77-91.
2. Albanus L, Heilberonn E, Sundwall A. Antidote effect of sodium fluoride in organophosphorus anticholinesterase poisoning. Biochem Pharmacol, 1965; 14: 1375-1381.
3. Anders MW, Stevens JL, Sprague RW, Shaath Z, Ahmed AE. Metabolism of haloforms to carbon monoxide. II. In vivo studies. Drug Metab Dispos, 1978; 6: 556-560.
4. Andreescu S, Marty J. Twenty years research in cholinesterase biosensors: from basic research to practical applications. Biomol Eng, 2006; 23: 1-15.
5. Ansell M, Lewis FAS. A review of cyanide concentrations found in human organs: a survey of literature concerning cyanide metabolism, normal, non-fatal, and fatal cyanide levels. J Forensic Med, 1970; 17: 148-155.
6. Ballantyne C. Artifacts in the definition of toxicity by cyanides and cyanogens. Fundam Appl Toxicol, 1983; 3: 400-408.
7. 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 Anal Toxicol, 2004; 28: 371-378.
8. Barr JR, Young CL, Woolfit AR, et al. Comprehensive quantitative tandem MS analysis of urinary metabolites and albumin adducts following an accidental human exposure to sulfur mustard. In: Proceedings of the 53rd Conference of the American Society of Mass Spectrometry, San Antonio, TX, June 2005.
9. Benschop HP, De Jong LPA. Toxicokinetics of soman: species variation and stereospecificity in elimination pathways. Neurosci Biobehav Rev, 1991; 15: 73-77.
10. Benschop HP, De Jong LPA. Toxicokinetics of nerve agents. In: Somani SM, Romano JR, eds. Chemical Warfare Agents: Toxicity at Low Levels. Boca Raton, FL: CRC Press; 2001:25-81.
11. Benschop HP, van der Schans GV, Noort D, Fidder A, Mars-Groenendijk RH, de Jong LPA. Verification of exposure to sulfur mustard in two casualties of the Iran-Iraq conflict. J Anal Toxicol, 1997; 21: 249-251.
12. Benschop HP, Noort D, van der Schans GV, de Jong LPA. Diagnosis and dosimetry of exposure to sulfur mustard: development of standard operating procedures; further exploratory research on protein adducts. Final report for contract DAMD17-97-2-7002, ADA381035, 2000.
13. Black RM, Read RW. Detection of trace levels of thiodiglycol in blood, plasma and urine using gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry. J Chromatogr, 1988; 449: 261-270.
14. Black RM, Read RW. Methods for the analysis of thiodiglycol sulphoxide, a metabolite of sulphur mustard, in urine using gas chromatography-mass spectrometry. J Chromatogr, 1991a; 558:393-404.
15. Black RM, Read RW. Improved methodology for the detection and quantitation of urinary metabolites of sulphur mustard using gas chromatography-tandem mass spectrometry. J Chromatogr B, 1995a; 665:97-105.
16. Black RM, Read RW. Biological fate of sulphur mustard, 1, 10-thiobis(2-chloroethane): identification of b-lyase metabolites and hydrolysis products in human urine. Xenobiotica, 1995b; 25:167-173.
17. Black RM, Noort D. Methods for the retrospective detection of exposure to toxic scheduled chemicals. Part A: analysis of free metabolites. In: Mesilaakso M, ed. Chemical Weapons Convention Chemicals Analysis: Sample Collection, Preparation, and Analytical Methods. Chichester, West Sussex, England: John Wiley and Sons; 2005:403-431.
18. Black RM, Clarke RJ, Read RW. Analysis of 1, 10-sulphonylbis[2-(methylsulphinyl)ethane] and 1-methylsulphinyl-2-[2-(methylthio)ethylsulphonyl]ethane, metabolites of sulphur mustard, in urine using gas chromatography- mass spectrometry. J Chromatogr, 1991b; 558:405-414.
19. Black RM, Brewster K, Clarke RJ, Hambrook JL, Harrison JM, Howells DJ. Biological fate of sulphur mustard, 1, 10-thiobis(2-chloroethane): isolation and identification of urinary metabolites following intraperitoneal administration to rat. Xenobiotica, 1992a; 22:405-418.
20. Black RM, Hambrook JL, Howells DJ, Read RW. Biological fate of sulfur mustard, 1, 10-thiobis(2-chloroethane). Urinary excretion profiles of hydrolysis products and b-lyase metabolites of sulfur mustard after cutaneous application in rats. J Anal Toxicol, 1992b; 16:79-84.
21. Black RM, Harrison JM, Read RW. Biological fate of sulphur mustard: in vitro alkylation of human haemoglobin by sulphur mustard. Xenobiotica, 1997a; 27:11-32.
22. Black RM, Clarke RJ, Harrison JM, Read RW. Biological fate of sulphur mustard: identification of valine and histidine adducts in haemoglobin from casualties of sulphur mustard poisoning. Xenobiotica, 1997b; 27:499-512.
23. Black RM, Harrison JM, Read RW. The interaction of sarin and soman with plasma proteins: the identification of a novel phosphonylation site. Arch Toxicol, 1999; 73: 123-126.
24. Blakley RL, Coop IE. The metabolism and toxicity of cyanides and cyanogenic blycosides in sheep. NZ J Sci Technol, 1949; 31A(3):1-16.
25. Boettcher BMA. Synthesis of L-2-oxothiazolidine-4-carboxylic acid. Anal Biochem, 1984; 138: 449-450.
26. Bonierbale E, Debordes L, Coppet L. Application of capillary gas chromatography to the study of hydrolysis of the nerve agent VX in rat plasma. J Chromatogr B, 1996; 688: 255-264.
27. Borak J, Diller WF. Phosgene exposure: mechanisms of injury and treatment strategies. J Occup Environ Med, 2001; 43: 110-119.
28. Boyer AE, Ash D, Barr DB, et al. Quantitation of the sulfur mustard metabolites 1, 10-sulfonylbis[2-(methylthio)ethane] and thiodiglycol in urine using isotope-dilution gas chromatography-tandem mass spectrometry. J Anal Toxicol, 2004; 28: 327-332.
29. Byrd GD, Paule RC, Sander LC, Sniegoski LT. White E 5th, Bausum HT. Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry. J Anal Toxicol, 1992; 16: 182-187.
30. Calafat A, Stanfill S. Rapid quantitation of cyanide in whole blood by automated headspace gas chromatography. J Chromatogr B, 2002; 772: 131-137.
31. Capacio BR, Smith JR, DeLion MT, et al. Monitoring sulfur mustard exposure by gas chromatography- mass spectrometry analysis of thiodiglycol cleaved from blood proteins. J Anal Toxicol, 2004; 28: 306-310.
32. Carroll LS. Images in clinical toxicology: sulfur mustard cutaneous exposure. Clin Toxicol, 2005; 1:55.
33. Chattaraj S, Das AK. Indirect determination of thiocyanate in biological fluids using atomic absorption spectrometry. Spectrochica, 1992; 47(5):675-680.
34. Chemistry Business, Focused on Phosgene. 30.4, May 2002; 30-31.
35. Chen S-H, Wu S-M, Kou H-S, et al. Electron-capture gas chromatography determination of cyanide iodide, nitrite, sulfide and thiocyanate ions by phase-transfer-catalyzed derivatization with pentafluorobenzyl bromide. J Anal Toxicol, 1994; 18: 81-85.
36. Clement JG. Importance of aliesterase as a detoxification mechanism for soman (pinacolyl methylphosphonofluoridate) in mice. Biochem Pharmacol, 1984; 33: 3807-3811.
37. Clement JG, Benschop HP, De Jong LPA, Wolthuis OL. Stereoisomers of soman (pinacolyl methylphosphonofluoridate): inhibition of serum carboxylic ester hydrolase and potentiation of their toxicity by CBDP (2-2-methylphenoxy)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide in mice. Toxicol Appl Pharmacol, 1987; 89: 141-143.
38. Cowlen MS, Hewitt WR, Schroeder F. 2-Hexanone potentiation of [14C]chloroform hepatotoxicity: covalent interaction of a reactive intermediate with rat liver phospholipid. Toxicol Appl Pharmacol, 1984; 73: 478-491.
39. Cucinell SA. Review of the toxicity of long-term phosgene exposure. Arch Environ Health, 1974; 28: 272-275.
40. De Biasi A, Sbraccia M, Keizer J, Testai E, Vittozzi L. The regioselective binding of chloroform reactive intermediates to microsomal phospholipids. Chem Biol Interact, 1992; 85: 229-242.
41. Degenhardt CEAM, Pleijsier K, van der Schans MJ, et al. Improvements of the fluoride reactivation method for the verification of nerve agent exposure. J Anal Toxicol, 2004; 28: 364-371.
42. De Jong LPA, Van Dijk C. Formation of soman (1, 2, 2-trimethylpropyl-methylphosphonofluoridate) via fluoride-induced reactivation of soman-inhibited aliesterase in rat plasma. Biochem Pharmacol, 1984; 33: 663-669.
43. Department of the US Army. Assay Techniques for Detection of Exposure to Sulfur Mustard, Cholinesterase Inhibitors, Sarin, Soman, GF, and Cyanide. Washington, DC: Headquarters, DA; May 1996. Technical Bulletin Medical 296.
44. Di Consiglio E, De Angelis G, Testai E, Vittozzi L. Correlation of a specific mitochondrial phospholipidphosgene adduct with chloroform acute toxicity. Toxicology, 2001; 159: 43-53.
45. Diller WF. Medical phosgene problems and their possible solution. J Occup Med, 1978; 20: 189-193.
46. Diller WF. Pathogenesis of phosgene poisoning. Toxicol Ind Health, 1985; 1:7-15.
47. Diller WF, Zante R. Dose-effect relations in the effects of phosgene on man and animals. Literature review. Zentralbl Arbeitsmed Arbeitsschutz Prophyl Ergonomie, 1982; 32:360-364, 366-368.
48. Doctor BP, Toker L, Roth E, Silman I. Microtiter assay for acetylcholinesterase. Anal Biochem, 1987; 166: 399-403.
49. Drasch G, Kretschmer E, Kauert G, von Meyer L. Concentrations of mustard gas [bis(2-chloroethyl)sulfide] in the tissues of a victim of vesicant exposure. J Forensic Sci, 1987; 32: 1788-1793.
50. Driskell WJ, Shih ML, Needham LL, Barr DB. Quantitation of organophosphorus nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass spectrometry. J Anal Toxicol, 2002; 26: 6-10.
51. Egekeze JO, Oehme FW. Direct potentiometric method for the determination of cyanide in biological materials. J Anal Toxicol, 1979; 3: 119-124.
52. Ellin RI, Burkhardt BH, Hart RD. A time-modified method for measuring red blood cell cholinesterase activity. Arch Environ Health, 1973; 27: 48-49.
53. Ellman GL, Courtney KD, Anders V, Featherstone RM. A new and rapid colorimetric determination of cholinesterase activity. Biochem Pharm, 1961; 7: 88-95.
54. Ember L. Probe of troop’s exposure to chemical arms failed. Chem Eng News, 1996; 23:40-41
55. Eyer P, Worek F, Kiderlen D, Sinko G, Stuglin A, Simeon-Rudolf V, Reiner E. Molar absorption coefficients for the reduced Ellman reagent: reassessment. Anal Biochem, 2003; 312: 224-227.
56. Fabrizi L, Taylor GW, Edwards RJ, Boobis AR. Adducts of the chloroform metabolite phosgene. Adv Exp Med Biol, 2001; 500: 129-132.
57. Farooqui MYH, Ahmed AE. Molecular interaction of acrylonitrile and potassium cyanide with rat blood. Chem Biol Interact, 1982; 38: 145-159.
58. Fidder A, Moes GWH, Scheffer AG, et al. Synthesis, characterization, and quantitation of the major adducts formed between sulfur mustard and DNA of calf thymus and human blood. Chem Res Toxicol, 1994; 7: 199-204.
59. Fidder A, Noort D, de Jong LPA, Benschop HP, Hulst AG. N7-(2-hydroxyethylthioethyl)-guanine: a novel urinary metabolite following exposure to sulphur mustard. Arch Toxicol, 1996a; 70:854-855.
60. Fidder A, Noort D, de Jong AL, Trap HC, de Jong LPA, Benschop HP. Monitoring of in vitro and in vivo exposure to sulfur mustard by GC/MS determination of the N-terminal valine adduct in hemoglobin after a modified Edman degradation. Chem Res Toxicol, 1996b; 9:788-792.
61. Fidder A, Noort D, Hulst AG, de Jong LPA, Benschop HP. Biomonitoring of exposure to lewisite based on adducts to hemoglobin. Arch Toxicol, 2000; 74: 207-214.
62. Fidder A, Hulst D, Noort D, et al. Retrospective detection of exposure to organophosphorus anti-cholinesterases: mass spectrometric analysis of phosphylated human butyrylcholinesterase. Chem Res Toxicol, 2002; 15: 582-590.
63. Fredriksson S-Å, Hammarström L-G, Henriksson L, Lakso H-Å. Trace determination of alkyl methylphosphonic acids in environmental and biological samples using gas chromatography/negative-ion chemical ionization mass spectrometry and tandem mass spectrometry. J Mass Spectrom, 1995; 30: 1133-1143.
64. Ganjeloo A, Isom GE, Morgan RL, et al. Fluorometric determination of cyanide in biological fluids with p-benzoquinone. Toxicol Appl Pharmacol, 1980; 55: 103-107.
65. Gardner J, Gibbons RV, Hooper TI, Cunnion SO, Kroeenke K, Gackstetter, GD. Identifying new diseases and their causes: the dilemma of illnesses in Gulf War veterans. Mil. Med, 2003; 168: 186-193.
66. Gordon RK, Doctor BP. Immobilized enzymes biosensors for chemical toxins. US Patent Trade Office #6, 406, 876, 2002; 18 June.
67. Gordon RK, Doctor BP, Chiang PK. A radioactive assay for acetylcholinesterase using anion-exchange disk. Anal. Biochem, 1982; 124: 333-337.
68. Gordon RK, Haigh JR, Garcia GE, Feaster SR, Riel MA, Lenz DE, Aisen PS, Doctor BP. Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman. Chem Biol Interact, 2005; 157-158:239-246.
69. Guastadisegni C, Guidoni L, Balduzzi M, Viti V, Di Consiglio E, Vittozzi L. Characterization of a phospholipid adduct formed in Sprague Dawley rats by chloroform metabolism: NMR studies. J Biochem Mol Toxicol, 1998; 12: 93-102.
70. Guastadisegni C, Balduzzi M, Mancuso MT, Di Consiglio E. Liver mitochondria alterations in chloroformtreated Sprague-Dawley rats. J Toxicol Environ Health A, 1999; 57: 415-429.
71. Gwilt PR, Radick LE, Xiao-Yan L, Whalen JJ, Leaf CD. Pharmacokinetics of 2-oxothiazolidine-4-carboxylate, a cysteine prodrug, and cysteine. J Clin Pharmacol, 1998; 38: 945-950.
72. Harris LW, Braswell LM, Fleisher JP, Cliff WJ. Metabolites of pinacolyl methylphosphonofluoridate (Soman) after enzymatic hydrolysis in vitro. Biochem Pharmacol, 1964; 13: 1129-1136.
73. Hayes TL, Kenny DV, Hernon-Kenny L. Feasibility of direct analysis of saliva and urine for phosphonic acids and thiodiglycol-related species associated with exposure to chemical warfare agents using LC-MS/MS. J Med Chem Def, 2004; 2: 1-23.
74. Heilbronn E. The effect of sodium fluoride on sarin inhibited blood cholinesterase. Acta Chem Scand, 1964; 18:2410.
75. Heilbronn E. Action of fluoride on cholinesterase. II. In vitro reactivation of cholinesterase inhibited by organophosphorus compounds. Biochem Pharmacol, 1965; 14: 1363-1373.
76. Jakubowski EM, Woodard CL, Mershon MM, Dolzine TW. Quantification of thiodiglycol in urine by electron ionization gas chromatography-mass spectrometry. J Chromatogr, 1990; 528: 184-190.
77. Jakubowski EM, Smith JR, Logan TP, et al. Verification of lewisite exposure: quantification of chlorovinylarsonous acid in biological samples. In: Proceedings of the 1993 Medical Defense Bioscience Review, Aberdeen Proving Ground, MD: US Army Medical Research Institute of Chemical Defense, 1993:361-368, AD A275667.
78. Jakubowski EM, Sidell FR, Evans RA, et al. Quantification of thiodiglycol in human urine after an accidental sulfur mustard exposure. Toxicol Methods, 2000; 10: 143-150.
79. Jakubowski EM, Heykamp LS, Durst HD, Thompson SA. Preliminary studies in the formation of ethyl methylphosphonofluoridate from rat and human serum exposed to VX and treated with fluoride ion. Anal Lett, 2001; 34: 727-737.
80. Jakubowski EM, McGuire JM, Evans RA, et al. Quantitation of fluoride ion released sarin in red blood cell samples by gas chromatography-chemical ionization mass spectrometry using isotope dilution and largevolume injection. J Anal Toxicol, 2004; 28: 357-363.
81. Johnson CD, Russell RL. A rapid, simple radiometric assay for cholinesterase, suitable for multiple determinations. Anal Biochem, 1975; 64: 229-238.
82. Jugg B, Jenner J, Rice P. The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids. Hum Exp Toxicol, 1999; 18: 659-668.
83. Katagi M, Nishikawa M, Tatsuno M, Tsuchihashi H. Determination of the main hydrolysis products of organophosphorus nerve agents, methylphosphonic acids, in human serum by indirect photometric detection ion chromatography. J Chromatogr B, 1997; 698: 81-88.
84. Keilin D. Cytochrome and respiratory enzymes. Proc R Soc Lond B Biol Sci, 1929; 104: 206-251.
85. Kling A. Acute pulmonary edema following exposure to war gases. Comptes Rendus De L’Academie des Sciences, 1933; 197: 1782-1784.
86. Korte WD, Walker EM, Smith JR, et al. The determination of sulfur mustard exposure by analysis of blood protein adducts. Wehrmed. Mschr, 2005; 49:327.
87. Kubic VL, Anders MW. Metabolism of carbon tetrachloride to phosgene. Life Sci, 1980; 26: 2151-2155.
88. Laforge M, Buneaux F, Houeto P, et al. A rapid spectrophotometric blood cyanide determination applicable to emergency toxicology. J Anal Toxicol, 1994; 18: 173-175.
89. Levin BC, Rechani PR, Gruman JL, et al. Analysis of carboxyhemoglobin and cyanide in blood of victims of the DuPont Plaza Hotel fire in Porto Rico. J Forensic Sci, 1990; 35: 151-168.
90. Li HZ, Bai G, Sun RM, et al. Determination of thiocyanate metabolite of sodium nitroprusside in serum by spectrophotometry. Yao Xue Xue Bao, 1993; 28: 854-858.
91. Little PJ, Reynolds ML, Bowman ER, Martin BR. Tissue disposition of [3H]sarin and its metabolites in mice. Toxicol Appl Pharmacol, 1986; 83: 412-419.
92. Liu X, Yun Z. High-performance liquid chromatographic determination of thiocyanate anions by derivatization with pentafluorobenzyl bromide. J Chromatogr A, 1993; 653: 348-353.
93. Logan TP, Smith JR, Jakubowski EM, Nielson RE. Verification of lewisite exposure by the analysis of 2-chlorovinyl arsonous acid in urine. Toxicol Methods, 1999; 9: 275-284.
94. Logue BA, Kirschten NP, Petrovics I, Moser MA, Rockwood GA, Baskin SI. Determination of the cyanide metabolite 2-aminothiazole-4-carboxylic acid in urine and plasma by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci, 2005; 819: 237-244.
95. Lotti M. Cholinesterase inhibition: complexities in interpretation. Clin Chem, 1995; 41: 1814-18.
96. Ludlum DB, Austin-Ritchie P, Hagopian M, Niu T-Q, Yu D. Detection of sulfur mustard-induced DNA modifications. Chem Biol Interact, 1994; 91: 39-49.
97. Lundquist P, Kagedal B, Nilsson L, Rosling H. Analysis of the cyanide metabolite 2-aminothiazoline-4-carboxylic acid in urine by high-performance liquid chromatography. Anal Biochem, 1995; 228: 27-34.
98. Malveda M. CEH product review: phosgene. Chemical Economics Handbook-SRI International, 2003; 687.
99. Mathur BB, Krishna G. Toxicodynamics of phosgene. In: Somani S, ed. Chemical Warfare Agents. San Diego, SA: Academic Press, Inc. 1992:237-254.
100. Matsuda Y, Nagao M, Takatori T, Niijima H, Nakajima M, Iwase H, Kobayashi M, Iwadate K. Detection of the sarin hydrolysis product in formalin-fixed brain tissues of victims of the Tokyo subway terrorist attack. Toxicol Appl Pharmacol, 1998; 150: 310-320.
101. Maxwell DM, Brecht KM. Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds. J Appl Toxicol, 2001; 21 (Suppl 1):S103-S107.
102. Maxwell DM, Brecht KM, O’Neill BL. The effect of carboxylesterase inhibition on interspecies differences in soman toxicity. Toxicol Lett. 1987; 39:35-42.
103. McMillan DE, Svoboda AC. The role of erythrocytes in cyanide detoxification. J Pharmacol Exp Ther, 1982; 221: 37-42.
104. Michel HO. An electrometric method for the determination of red blood cell and plasma cholinesterase activity. J Lab Clin Med, 1949; 34: 1564-1568.
105. Michigami Y, Fujii K, Ueda K, et al. Determination of thiocyanate in human saliva and urine by ion chromatography. Analyst (U.K.), 1992; 117: 1855-1858.
106. Miki A, Katagi M, Tsuchihashi H, Yamashita M. Determination of alkylmethylphosphonic acids, the main metabolites of organophosphorus nerve agents, in biofluids by gas chromatography-mass spectrometry and liquid-liquid-solid-phase-transfer-catalyzed pentafluorobenzylation. J Anal Toxicol, 1999; 23: 86-93.
107. Minami M, Hui D-M, Katsumata M, Inagaki H, Boulet CA. Method for the analysis of methylphosphonic acid metabolites of sarin and its ethanol-substituted analogue in urine as applied to the victims of the Tokyo sarin disaster. J Chromatogr B, 1997; 695: 237-244.
108. Miura Y, Koh T. Determination of thiocyanate in human urine samples by suppressed ion chromatography. Anal Sci, 1991; 7(Suppl Proc Int Congr Anal Sci, 1991, Pt 1):167-170.
109. Morgan RL, Way JL. Fluorometric determination of cyanide in biological fluids with pyrudixal. J Anal Toxicol, 1980; 4: 78-81.
110. Mortensen SR, Brimijohn S, Hooper MJ, Padilla S. Comparison of the in vitro sensitivity of rat acetylcholinesterase to chlorpyrifos-oxon: what do tissue IC50 values represent? Toxicol Appl Pharmacol, 1998; 148: 46-49.
111. Nagao M, Takatori T, Matsuda Y, Nakajima M, Niijima H, Iwase H, Iwadate K, Amano T. Detection of sarin hydrolysis products from sarin-like organophosphorus agent-exposed human erythrocytes. J Chromatogr B, 1997a; 701:9-17.
112. Nagao M, Takatori T, Matsuda Y, Nakajima M, Iwase H, Iwadate K. Definitive evidence for the acute sarin poisoning diagnosis in the Tokyo subway. Toxicol Appl Pharmacol, 1997b; 144:198-203.
113. Nakajima T, Sasaki K, Ozawa H, Sekijima Y, Mortia H, Fukushima Y, Yanagisawa N. Urinary metabolites of sarin in a patient of the Matsumoto incident. Arch Toxicol, 1998; 72: 601-603.
114. National Research Council (US) Committee on Toxicology. The National Academy of Sciences, ed. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants. Washington, DC: National Academy Press; 1984, Vol. 1.
115. Nigg HN, Knaak JB. Blood cholinesterases as human biomarkers of organophosphorus pesticide exposure. Rev Environ Contam Toxicol, 2000; 163: 29-111.
116. NIOSH. Pocket. 2004: National Institute for Occupational Health and Safety.
117. Noort D, Black RM. Methods for the retrospective detection of exposure to toxic scheduled chemicals. Part B: mass spectrometric and immunochemical analysis of covalent adducts to proteins and DNA. In: Mesilaakso M, ed. Chemical Weapons Convention Chemicals Analysis: Sample Collection, Preparation, and Analytical Methods, Chichester, West Sussex, England: John Wiley and Sons; 2005:433-451.
118. Noort D, Verheij ER, Hulst AG, de Jong LPA, Benschop HP. Characterization of sulfur mustard induced structural modifications inhuman hemoglobin by liquid chromatography-tandem mass spectrometry. Chem Res Toxicol, 1996; 9: 781-787.
119. Noort D, Hulst AG, Trap HC, de Jong LPA, Benschop HP. Synthesis and mass spectrometric identification of the major amino acid adducts formed between sulphur mustard and haemoglobin in human blood. Arch Toxicol, 1997; 71: 171-178.
120. Noort D, Hulst A, Platenburg DHJM, Polhuijs M, Benschop H. Quantitative analysis of O-isopropyl methylphosphonic acid in serum samples of Japanese citizens allegedly exposed to sarin: estimation of internal dosage. Arch Toxicol, 1998; 72: 671-675.
121. Noort D, Hulst AG, de Jong LPA, Benschop HP. Alkylation of human serum albumin by sulfur mustard in vitro and in vivo: mass spectrometric analysis of a cysteine adduct as a sensitive biomarker of exposure. Chem Res Toxicol, 1999; 12: 715-721.
122. Noort D, Fidder A, Hulst AG, de Jong LPA, Benschop HP. Diagnosis and dosimetry of exposure to sulfur mustard: development of a standard operating procedure for mass spectrometric analysis of haemoglobin adducts: exploratory research on albumin and keratin adducts. J Appl Toxicol, 2000a; 20:S187-S192.
123. Noort D, Hulst AG, Fidder A, van Gurp RA, de Jong LP, Benschop HP. In vitro adduct formation of phosgene with albumin and hemoglobin in human blood. Chem Res Toxicol, 2000b; 13:719-726.
124. Noort D, Benschop HP, Black RM. Biomonitoring of exposure to chemical warfare agents: a review. Toxicol Appl Pharmacol, 2002; 184: 116-126.
125. Noort D, Fidder A, Benschop HP, de Jong LPA, Smith JR. Procedure for monitoring exposure to sulfur mustard based on modified Edman degradation of globin. J Anal Toxicol, 2004a; 28:311-315.
126. Noort D, Fidder A, Hulst AG, Woolfitt AR, Ash D, Barr JR. Retrospective detection of exposure to sulfur mustard: improvements on an assay for liquid chromatography-tandem mass spectrometry analysis of albumin/sulfur mustard adducts. J Anal Toxicol, 2004b; 28:333-338.
127. Noort D, Fidder A, van der Schans MJ, Hulst AG. Verification of exposure to organophosphates: generic mass spectrometric method for detection of human butyrylcholinesterase adducts. Anal Chem, 2006; 78: 6640-6644.
128. Odoul M, Fouillet B, Nouri B, et al. Specific determination of cyanide in blood by headspace gas chromatography. J Anal Toxicol, 1994; 18: 205-207.
129. Parshall, G.W. Trends in processing and manufacturing that will affect implementation of the Chemical Weapons Convention. Pure Appl Chem, 2002; 74: 2259-2263.
130. Parvari R, Pecht I, Soreq H. A microfluorometric assay for cholinesterases, suitable for multiple kinetic determinations of picomoles of released thiocholine. Anal Biochem, 1983; 133: 450-456.
131. Pastore A, Massoud R, Motti C, et al. Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine and 2-mercaptopropionylglycine in plasma and urine. Clin Chem, 1998; 44: 825-832.
132. Pastore AFG, Bertini E, Piemonte F. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta, 2003; 333: 19-39.
133. Pereira MA, Chang LW, Ferguson JL, Couri D. Binding of chloroform to the cysteine of hemoglobin. Chem Biol Interact, 1984; 51: 115-124.
134. Pettigrew AR, Fell GS. Simplified colorimetric determination of thiocyanate in biological fluid and its application to the study of conversion of cyanide to thiocyanate. Clin Chem, 1972; 18: 996-1000.
135. Pohl LR, Branchflower RV, Highest RJ, et al. The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride. Drug Metab Dispos, 1981; 9: 334-339.
136. Polak RL, Cohen EM. The influence of oximes on the distribution of 32P in the body of the rat after injection of 32P-sarin. Biochem Pharmacol, 1970; 19: 865-876.
137. Polednak AP. Mortality among men occupationally exposed to phosgene in 1943-1945. Environ Res, 1980; 22: 357-367.
138. Polhuijs M, Langenberg JP, Benschop HP. New method for retrospective detection of exposure to organophosphorus anticholinesterases: application to alleged sarin victims of Japanese terrorists. Toxicol Appl Pharmacol, 1997; 146: 156-61.
139. Polhuijs M, Langenberg JP, Noort D, Hulst AG, Benschop HP. Retrospective detection of exposure to organophosphates: analyses in blood of human beings and rhesus monkeys. In: Sohns T, Voicu VA, eds. NBC Risks: Current Capabilities and Future Perspectives for Protection, Dordrecht, The Netherlands: Kluwer Academic Publishers; 1999:513-521.
140. Porta P, Aebi S, Summer K, Lauterburg BH. L-2-Oxothiazolidine-4-carboxylic acid, a cysteine prodrug: pharmacokinetics and effects on thiols in plasma and lymphocytes in human. J Pharmacol Exp Ther, 1991; 257: 331-334.
141. Price EO, Smith JR, Clark CR, Schlager JJ, Shih ML. MALDI-TOF/MS as a diagnostic tool for the confirmation of chemical agent exposure. J Appl Toxicol, 2000; 20:S193-S197.
142. Read RW, Black RM. Analysis of b-lyase metabolites of sulfur mustard in urine by electrospray liquid chromatography-tandem mass spectrometry. J Anal Toxicol, 2004a; 28:346-351.
143. Read RW, Black RM. Analysis of the sulfur mustard metabolite 1, 10-sulfonylbis[2-S-(N-acetylcysteinyl) ethane] in urine by negative ion electrospray liquid chromatography-tandem mass spectrometry. J Anal Toxicol, 2004b; 28:352-356.
144. Reed DJ, Fariss MW. Glutathione depletion and susceptibility. Pharmacol Rev, 1994; 36: 235-335.
145. Reynolds ML, Little PJ, Thomas BF, Bagley RB, Martin BR. Relationship between the disposition of [3H] soman and its pharmacological effects in mice. Toxicol Appl Pharmacol, 1985; 80: 409-420.
146. Richie JP Jr, Skowronski L, Abraham P, Leutzinger Y. Blood glutathione concentrations in a large-scale human study. Clin Chem, 1996; 42: 64-70.
147. Rieders F. Noxious gases and vapors: I. Carbon monoxide, cyanides, memoglobin, and sulfhemoglobin. In: Dipalma J, ed. Drill’s Pharmacology in Medicine. New York, NY: McGraw-Hill; 1971:1189-1205.
148. Sandelowsky I, Simon GA, Bel P, Barak R, Vincze A. N1-(2-hydroxyethylthioethyl)-4-methylimidazole (4-met-1-imid-thiodiglycol) in plasma and urine: a novel metabolite following dermal exposure to sulphur mustard. Arch Toxicol, 1992; 66: 296-297.
149. Sano A, Takezawa M, Takitani S. Spectrofluorometric determination of cyanide in blood and urine with naphthalene-2, 3-dialdehyde and taurine. Anal Chim Acta, 1989; 225: 351-358.
150. Sano A, Takimoto N, Takitani S. High-performance liquid chromatographic determination cyanide in human red blood cells by pre-column fluorescence derivatization. J. Chromatogr, 1992; 582: 131-135.
151. Sartori, M. The War Gases. 1939, New York, NY: D. Van Nostrand.
152. Sciuto AM. Assessment of early acute lung injury in rodents exposed to phosgene. Arch Toxicol, 1998; 72: 283-288.
153. Sciuto AM, Hurt HH. Therapeutic treatments of phosgene-induced lung injury. Inhal Toxicol, 2004; 16: 565-580.
154. Sciuto AM, Stotts RR, Chittenden V, Choung E, Heflin MD. Changes in absorbance at 413 nm in plasma from three rodent species exposed to phosgene. Biochem Biophys Res Commun, 1996; 226: 906-911.
155. Sciuto AM, Strickland PT, Kennedy TP, Gurtner GH. Postexposure treatment with aminophylline protects against phosgene-induced acute lung injury. Exp Lung Res, 1997; 23: 317-332.
156. Sciuto AM, Cascio MB, Moran TS, Forster JS. The fate of antioxidant enzymes in bronchoalveolar lavage fluid over 7 days in mice with acute lung injury. Inhal Toxicol, 2003; 15: 675-685.
157. Seto Y. Stability and spontaneous production of blood cyanide during heating. J Forensic Sci, 1996; 41: 465-468.
158. Seto Y, Tsunoda N, Ohta H, et al. Determination of blood cyanide by headspace gas chromatography with nitrogen phosphorus detection and using a megabore capillary column. Anal Chim Acta, 1993; 276: 247-259.
159. Shih ML, Smith JR, McMonagle JD, Dolzine TW, Gresham VC. Detection of metabolites of toxic alkylmethylphosphonates in biological samples. Biol Mass Spectrom, 1991; 20: 717-723.
160. Shih ML, McMonagle JD, Dolzine TW, Gresham VC. Metabolite pharmacokinetics of soman, sarin, and GF in rats and biological monitoring of exposure to toxic organophosphorus agents. J Appl Toxicol, 1994:14:195-199.
161. 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 Textbook of Military Medicine. Part I.Washington, DC: Department of the Army, Office of The Surgeon General, and Borden Institute; 1997:129-179.
162. Silver A. The biology of cholinesterases. In: Neuberger A, Tatum EL, eds. North-Holland Research Monographs: Frontiers of Biology. Vol 36. Amsterdam: North Holland Publishing Co; 1974:58-67.
163. Smith JR, Logan TP, Szafraniec LL, Jakubowski EM. Spectroscopic characterization of the geminal isomer of lewisite. Anal Lett, 1995; 28: 1541-1554.
164. Smith RP. Toxic responses of the blood. In: Klaassen CD, Amdur MO, Doull J, eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons. 5th ed. New York: McGraw-Hill; 1996:335-354.
165. St. Omer VEV, Rottinghaus GE. Biochemical determination of cholinesterase activity in biological fluids and tissues. In: Ballantyne B, Marrs TC, eds. Clinical and Experimental Toxicology of Organophosphates and Carbamates. Oxford: Butterworth and Heinemann; 1992:15-27.
166. Suzuki T, Morita H, Ono K, Maekawa K, Nagai R, Yazaki Y. Sarin poisoning in Tokyo subway [letter]. Lancet, 1995; 345:980.
167. Taylor P. Anticholinesterase agents. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006:201-216.
168. Taylor PW, Lukey BJ, Clark CR, Lee RB, Roussel RR. Field verification of Test-mate ChE. Mil Med. 2003; 168:314-319.
169. Tominaga MY, Midio AF. Modified method for the determination of thiocyanate in urine by ion-exchange chromatography and spectrophotometry. Rev Farm Bioquim Univ Sao Paulo, 1991; 27: 100-105.
170. Tomoda A, Hashimoto K. The determination of cyanide in water and biological tissues by methemoglobin. J Hazard Mater, 1991; 28: 241-249.
171. Toxicological profile for cyanide, published by U.S. Department of Health and Human Services, Public Health Services, Agency for Toxic Substances and Disease Registry, 1997.
172. Tracqui A, Raul JS, Geraut A, Berthelon L, Lude B. Determination of blood cyanide by HPLC-MS. J Anal Toxicol, 2002; 26: 144-148.
173. Tsuchihashi H, Katagi M, Nishikawa M, Tatsuno M. Identification of metabolites of nerve agent VX in serum collected from a victim. J Anal Toxicol, 1998; 22: 383-388.
174. United Nations. Report of the mission dispatched by the Secretary-General to investigate allegations of the use of chemical weapons in the conflict between the Islamic Republic of Iran and Iraq. United Nations Report No. S/17911, 12 March 1986.
175. van der Schans GP, Scheffer AG, Mars-Groenendijk RH, Fidder A, Benschop HP, Baan RA. Immunochemical detection of adducts of sulfur mustard to DNA of calf thymus and human white blood cells. Chem Res Toxicol, 1994; 7: 408-413.
176. van der Schans GP, Noort D, Mars-Groenendijk RH, et al. Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin. Chem Res Toxicol, 2002; 15: 21-25.
177. van der Schans GP, Noort D, Mars-Groenendijk RH, de Jong LPA, Benschop HP, Noort D. Standard operating procedure for immunuslotblot assay for analysis of DNA/sulfur mustard adducts in human blood and skin. J Anal Toxicol, 2004; 28: 316-319.
178. van der Schans MJ, Lander BJ, van der Wiel H, Langenberg JP, Benschop HP. Toxicokinetics of the nerve agent (±)VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration. Toxicol Appl Pharmacol, 2003; 191: 48-62.
179. Vycudilik W. Detection of mustard gas bis(2-chloroethyl)-sulfide in urine. Forensic Sci Int, 1985; 28: 131-136.
180. Vycudilik W. Detection of bis(2-chloroethyl)-sulfide (yperite) in urine by high resolution gas chromatographymass spectrometry. Forensic Sci Int, 1987; 35: 67-71.
181. Warburg O. Inhibition of the action of prussic acid in living cells. Hoppe Seyler’s Z Physiol Chem, 1911; 76: 331-346.
182. Waters WA, Williams JH. Hydrolyses and derivatives of some vesicant arsenicals. J Chem Soc, 1950; 18-22.
183. Way JL. Cyanide intoxication and its mechanism of antagonism. Annu Rev Pharmacol Exp Toxicol, 1984; 24: 451-481.
184. Willems JL. Clinical management of mustard gas casualties. Ann Med Milit Belg, 1989; 3S:1-61.
185. Wils ERJ, Hulst AG, de Jong AL, Verweij A, Boter HL. Analysis of thiodiglycol in urine of victims of an alleged attack with mustard gas. J Anal Toxicol, 1985; 9: 254-257.
186. Wils ERJ, Hulst AG, van Laar J. Analysis of thiodiglycol in urine of victims of an alleged attack with mustard gas, part II. J Anal Toxicol, 1988; 12: 15-19.
187. Wilson BW, Sanborn JR, O’Malley MA, Henderson JD, Billitti JR. Monitoring the pesticide-exposed worker. Occup Med, 1997; 12: 347-63.
188. Wolthuis OL, Benschop HP, Berends F. Persistence of the anti-cholinesterase soman in rats; antagonism with a non-toxic simulator of this organophosphate. Eur J Pharmacol, 1981; 69: 379-383.
189. Wood JL, Cooley SL. Detoxification of cyanide by cystine. J Biol Chem, 1956; 218: 449-457.
190. Wooten JV, Ashley DL, Calafat AM. Quantitation of 2-chlorovinylarsonous acid in human urine by automated solid-phase microextraction-gas chromatography-mass spectrometry. J Chromatogr B, 2002; 772: 147-153.
191. Worek F, Mast U, Kiderlen D, Diepold C, Eyer P. Improved determination of acetylcholinesterase activity in human whole blood. Clin Chem Acta, 1999; 288: 73-90.
192. Young CL, Ash D, Driskell WJ, et al. A rapid, sensitive method for the quantitation of specific metabolites of sulfur mustard in human urine using isotope-dilution gas chromatography-tandem mass spectrometry. J Anal Toxicol, 2004; 28: 339-345.