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Biomonitoring of exposure to lewisite based on adducts to haemoglobin

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Author: Fidder, A. · Noort, D. · Hulst, A.G. · Jong, · Benschop, H.P.
Institution: Prins Maurits Laboratorium TNO
Source:Archives of Toxicology, 4-5, 74, 207-214
Identifier: 235734
doi: doi:10.1007/s002040000117
Keywords: Toxicology · Adducts · Electrospray mass spectroscopy · Gas chromatography-mass spectroscopy · Haemoglobin · 2 chlorovinylarsonous acid · Arsenic acid derivative · Beta globin · Dimercaprol · Hemoglobin · Imidazole derivative · Lewisite · Unclassified drug · Animal experiment · Biological monitoring · Chemical warfare · Controlled study · Erythrocyte · Gas chromatography · Guinea pig · Health hazard · Human · Human cell · Male · Mass spectrometry · Nonhuman · Radioactivity · Urinalysis · Animals · Arsenicals · Binding Sites · Carbon Radioisotopes · Chelating Agents · Dimercaprol · Environmental Exposure · Erythrocytes · Gas Chromatography-Mass Spectrometry · Globins · Guinea Pigs · Hemoglobins · Humans · Imidazoles · Male · Protein Binding · Mass spectrometry · Electrospray ionization · 1-(heptafluorobutyryl)imidazole, 32477-35-3 · 2-chlorovinylarsonous acid · Arsenicals · Carbon radioisotopes · Chelating agents · Dimercaprol, 59-52-9 · Globins, 9004-22-2 · Hemoglobins · Imidazoles · Lewisite, 541-25-3


The development of a procedure for retrospective detection and quantitation of exposure to the arsenical dichloro(2-chlorovinyl)arsine (lewisite; L1) has been initiated. Upon incubation of human blood with [14C]L1 (20 nM-0.2 mM) in vitro, more than 90% of the total radioactivity was found in the erythrocytes and 25-50% of the radioactivity becomes associated with globin. Evidence was obtained for the presence of several binding sites. One type of binding was identified as L1-induced crosslinking of cysteine residues 93 and 112 of the β-globin chain. A method was developed for extraction of bound and unbound 2-chlorovinylarsonous acid (CVAA), a major metabolite of L1, from whole blood after treatment with 2,3-dimercapto-1-propanol (BAL). Subsequent to derivatization with heptafluorobutyryl imidazole, the CVAA-BAL derivative could be analysed at a 40-fmol level by means of gas chromatography-mass spectroscopy (GC-MS) under electron impact conditions. With this procedure, in vitro exposure of human blood to 1 nM L1 could be determined. The same procedure was applied to the analysis of human urine samples spiked with CVAA. In vivo exposure of guinea pigs could be established at least 240 h after subcutaneous administration of the agent (0.25 mg/kg) by the determination of bound and unbound CVAA in the blood. In the urine of these animals, CVAA could be detected for 12 h after exposure.