Title
Biomonitoring of exposure to lewisite based on adducts to haemoglobin
Author
Fidder, A.
Noort, D.
Hulst, A.G.
de Jong, L.P.A.
Benschop, H.P.
Prins Maurits Laboratorium TNO
Publication year
2000
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 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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:7ba27784-4dc7-4e9c-ae07-2b56de23e0a6
DOI
https://doi.org/10.1007/s002040000117
TNO identifier
235734
ISSN
0340-5761
Source
Archives of Toxicology, 74 (4-5), 207-214
Document type
article