title: Biomonitoring of exposure to lewisite based on adducts to haemoglobin.
abstract: 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.
authors.affiliation: Department of Chemical Toxicology, TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Fidder
authors.forename: D
authors.initials: D
authors.lastname: Noort
authors.forename: A G
authors.initials: AG
authors.lastname: Hulst
authors.forename: L P
authors.initials: LP
authors.lastname: de Jong
authors.forename: H P
authors.initials: HP
authors.lastname: Benschop
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000097:blood* / Q000652:urine; D001665:Binding Sites; D002250:Carbon Radioisotopes; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D004112:Dimercaprol / Q000097:blood / Q000494:pharmacology; D004781:Environmental Exposure; D004912:Erythrocytes / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005914:Globins / Q000378:metabolism; D006168:Guinea Pigs; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles; D008297:Male; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D005466:Fluorocarbons
chemical_list: D001152:Arsenicals; D002250:Carbon Radioisotopes; D002614:Chelating Agents; D004112:Dimercaprol; D005914:Globins; D006454:Hemoglobins; D007093:Imidazoles; C419383:2-chlorovinylarsonous acid; C035965:lewisite; C046634:1-(heptafluorobutyryl)imidazole; D005466:Fluorocarbons