Biomonitoring of exposure to lewisite based on adducts to haemoglobin

• Published in: Archives of toxicology Vol. 74; no. 4-5; pp. 207 - 214
• Main Authors: FIDDER, A, NOORT, D, HULST, A. G, DE JONG, L. P. A, BENSCHOP, H. P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.07.2000
• Subjects: Animals; Arsenicals - blood; Arsenicals - urine; Binding Sites; Biological and medical sciences; Carbon Radioisotopes; Chelating Agents - metabolism; Chelating Agents - pharmacology; Chemical and industrial products toxicology. Toxic occupational diseases; dichloro(2-chlorovinyl)arsine; Dimercaprol - blood; Dimercaprol - pharmacology; Environmental Exposure; Erythrocytes - metabolism; Gas Chromatography-Mass Spectrometry; Globins - metabolism; Guinea Pigs; Hemoglobins - metabolism; Humans; Imidazoles; Male; Medical sciences; Protein Binding; Spectrometry, Mass, Electrospray Ionization; Toxicology; Various organic compounds; Human; Urine; Rodentia; In vitro; Electrospray; Biological monitoring; Chemical warfare agent; Gas chromatography; In vivo; Vertebrata; Mammalia; Guinea pig; Animal; Hemoglobin; Qualitative analysis; Mass spectrometry; Molecular adduct; Quantitative analysis
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040000117

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 beta-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.