Lewisite metabolites

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). 

The number of methods to verify an exposure to lewisite is limited. Chlorovinylarsonous acid (CVAA) can be found as the main metabolite in urine, while this compound can also be found as an adduct to hemoglobin (see Table 54.3). The analyte can be analyzed with GC-MS using normal configurations. 

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