Lewisite biomarker

Arroyo, C.M., Burman, D.L., Kahler, D.W., Nelson, M.R., Corun, C.M., Guzman, J.J., Smith, M.A., Purcell, E.D., Hackley, B.E., Soni, S.D., Broomfield, C.A. (2004). TNF-alpha expression patterns as potential molecular biomarker for human skin cells exposed to vesicant chemical warfare agents sulfur mustard (HD) and Lewisite (L). Cell Biol. Toxicol. 20 345-59. 

Analytical Methods for Urine and Blood. Specific biomarkers of lewisite exposure are currently based on a very limited number of in vitro experiments (Jakubowski et al., 1993 Wooten et al., 2002) and animal studies (Logan et al., 1999 Fidder et al., 2000). Wooten et al. (2002) developed a solid-phase microextraction (SPME) headspace sampling method for urine samples followed by GC-MS analysis. It is the most sensitive method reported to date with a lower limit of detection of 7.4 pg/mL. Animal experiments have been limited in number and in their scope. In one study of four animals, guinea pigs were given a subcutaneous dose of lewisite (0.5 mg/kg). Urine samples were analyzed for CVAA using both GC-MS and GC coupled with an atomic emission spectrometer set for elemental arsenic (Logan et al., 1999). The excretion profile indicated a very rapid elimination of CVAA in the urine. The mean concentrations detected were 3.5 pg/mL, 250 ng/mL, and 50 ng/mL for the 0-8, 8-16, and 16-24 h samples, respectively. Trace level concentrations... 

Application to Human Exposure (Urine and Blood). To date, there have been no reports of the collection of biomedical samples from individuals with suspected lewisite exposure. Samples from such an incident will be critical for confirming the validity of assaying for the biomarkers observed in animal models. Additionally, the biomarkers that have been investigated in animal studies to date have indicated a rapid clearance in urine and less so for blood. This will obviously create severe problems for the retrospective determination of lewisite exposure beyond a few days at most when analyzing urine samples. The blood assay for both bound and free CVAA will potentially provide a longer opportunity for retrospective confirmation of exposure (based on one animal study), but also indicates a substantial decrease (90%) in concentration levels observed over a 10 day period. 

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