Chlorovinylarsonous acid

X. Chaudot, A. Tambute and M. Caude, Simultaneous extraction and derivatization of 2-chlorovinylarsonous acid from soils using supercritical and pressurized fluids, J. Chromatogr. A, 888, 327-333 (2000). 

Procedures based on GC/MS for the determination of the lewisite 1 decomposition product 2-chlorovinylarsonous acid (CVAA, CAS number 85090-33-1) in urine and blood have also been developed. In one procedure, CVAA is converted with BAL the resulting CVAA/BAL product isolated by SPE on a C18-cartridge and further derivatized with heptafluorobutyryl imidazole (51). A later developed procedure is based on the derivatization of CVAA with 1,3-propanedithiol followed by SPME isolation and GC/MS analysis. Using SIM at the molecular ion peaks, the limit of detection was determined at 7.4 pg per ml urine (52). 

J.V. Wooten, D.L. Ashley and A.M. Calafat, Quantitation of 2-chlorovinylarsonous acid in human urine by automated solid-phase microextraction-gas chromatography-mass spectrometry, J. Chromatogr., B, 772, 147-153 (2002). 

Lewisite is too reactive to be analyzed by LC. Even with GC, it leads to a rapid degradation of column performance. Lewisites 1 and 2 initially hydrolyze to 2-chlorovinylarsonous acid (CVAA) (26) and bis(2-chlorovinyl)arsenous acid (28), respectively. LC/MS analysis of these trivalent acids is problematic, giving very poor signal-to-noise ratios in both... 

The most generally applied method for determination of an arsenical is by atomic absorption spectrometry (AAS) after reduction of the compound to AsH3. However, this only provides an indication of the presence of the element as against a natural background. Lewisite rapidly hydrolyzes to 2-chlorovinylarsonous acid (CVAA see Figure 7) in an aqueous environment such as blood plasma, and analytical methods have focused mainly on the determination of CVAA (see Chapter 16). 

Figure 7. Chemical structures of 2-chlorovinyldichloroarsine (lewisite LI), 2-chlorovinylarsonous acid (CVAA), British Anti-Lewisite (BAL) and the CVAA-BAL complex...

Figure 8. Chemical structures of 2-chlorovinyldichloroarsine (Lewisite LI), 2-chlorovinylarsonous acid (CVAA), British Anti-Lewisite (BAL) and the CVAA-BAL complex. (Reprinted from Toxicology and Applied Pharmacology, Vol. 184, D. Noort,H.P. BenschopandR.M. Black, Biomonitoring of Exposure to Chemical Warfare Agents A Review, pages 116-126 (2002), with permission from Elsevier Science.)...

Atomic Absorption Spectrometry Acetylcholinesterase British Anti-Lewisite Carboxylesterase Central Nervous System Chemical Warfare Agent 2-chlorovinylarsonous Acid Enzyme-linked Immunosorbent Assay Environmental Protection Agency... 

Lewisite in soil may rapidly volatilize or may be converted to lewisite oxide due to moisture in the soil (Rosenblatt et al, 1975). The low water solubility suggests intermediate persistence in moist soil (Watson and Griffin, 1992). Both lewisite and lewisite oxide may be slowly oxidized to 2-chlorovinylarsonic acid (Rosenblatt et al, 1975). Possible pathways of microbial degradation in soil include epoxidation of the C=C bond and reductive deha-logenation and dehydrohalogenation (Morrill et al, 1985). Due to the epoxy bond and arsine group, toxic metabolites may result. Additionally, residual hydrolysis may result in arsenic compounds. Lewisite is not likely to bioaccumulate. However, the arsenic degradation products may bioaccumulate (Rosenblatt et al, 1975). 

Once incorporated, unbound lewisite is quickly hydrolyzed. Its predominant metabolite is 2-chlorovinylarsonous acid, CVAA (Figure 50.8). Analytical methods to confinn lewisite exposure have, at least in the past, focused on the detection and quantification of CVAA. However, Noort et al. (2002) also pointed out that due to the high affinity of arsenic towards sulfhydryl groups, adducts of lewisite/ CVAA and cysteine residues of proteins are formed. In an in vitro study, incubating " C-labeled lewisite with human blood samples, 90% of lewisite was found in erythrocytes, whereas 25 to 50% of arsenic was bound to globin. From these protein adducts, CVAA can be released to form an adduct with the antidote British Anti-Lewisite (BAL) (Fidder et al, 2000). The authors were also able to identify a specific protein adduct of lewisite formed with the cysteine residues 93 and 112 of P-globin. See Detection of DNA and protein adducts of vesicants, below, for analytical... 

Incubation of lewisite-protein adducts with BAL is capable of transferring its metabolite 2-chlorovinylarsonous acid (CVAA) into a BAL-CVAA derivative. This derivative can be quantified using GC-MS. The method is able to detect a 1 nM lewisite exposure of human blood in vitro (Fidder et al, 2000). 

Fowler, W.K., Stewart, D.C., Weinberg, D.S., Sarver, E.W. (1991). Gas chromatographic determination of lewisite hydrolysate,2-chlorovinylarsonous acid, after derivatization with 1,2-ethanedithiol J. Chromatogr. 558 235-43. 

Bossle, P.C., Pleva, S.G., and Martin, J.J. (1989). Determination of 2-chlorovinylarsonic acid in environmental waters by ion chromatography. Technical Report CRDEC-TR-206. U.S. Army Armament Munitions Chemical Command, Aberdeen Proving Ground, Maryland 21010-5423, 15 p. 

No detailed metabolism studies have been reported for lewisite I. It is rapidly hydrolysed to 2-chlorovinylarsonous acid (CVAA), which is excreted in the urine of experimental animals (Jakubowski et al., 1993 Logan et al., 1999). It appears to be excreted over a relatively short period. 

Bossle, P.C. (1991) Determination of 2-chlorovinylarsonic acid in environmental waters by ion chromatography, US Army Edgewood Research Development and Engineering Center. 

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