Lewisite, determination

The recent development and comparative application of modern separation techniques with regard to determination of alkylphosphonic acids and lewisite derivatives have been demonstrated. This report highlights advantages and shortcomings of GC equipped with mass spectrometry detector and HPLC as well as CE with UV-Vis detector. The comparison was made from the sampling point of view and separation/detection ability. The derivatization procedure for GC of main degradation products of nerve agents to determine in water samples was applied. Direct determination of lewisite derivatives by HPLC-UV was shown. Also optimization of indirect determination of alkylphosphonic acids in CE-UV was developed. Finally, the new instrumental development and future trends will be discussed. 

Kinoshita, K., Shikino, O., Seto, Y. and Raise, T. (2006) Determination of degradation compounds derived from Lewisite by high performance liquid chromatography/inductively coupled plasma-mass spectrometry. Applied Organometallic Chemistry, 20(9), 591-96. 

B.A. Tomkins, G.A. Sega and C.-H. Ho, Determination of Lewisite oxide in soil using solid-phase microextraction followed by gas chromatography with flame photometric or mass spectrometric detection, J. Chromatogr., A, 909, 13-28 (2001). 

I.N. Stan kov, A.A. Sergeeva and S.N. Tarasov, Trace determination of fi-chlorovinyldichloroar-sine (lewisite) in water, soil, and construction materials by gas chromatography, J. Anal. Chem., 55, 66-69 (2000). 

A special derivatization reaction is required for lewisite 1, which is so reactive that it cannot be determined by GC/MS in low quantities (e.g. below 10 ng per injection). It has been known for a long time that lewisite 1 reacts with compounds having an a, P-dithiol structure, such as 2,3-dimercaptopropanol-l (British-Anti-Lewisite (BAL) also used for medical treatment). The derivatization reaction can be performed at an analytical level and several examples have been described (29). The reaction product of lewisite 1 with 3,4-dimercaptotoluene, 2-(2-chlorovinyl)-5-methyl-l,3,2-benzodithiarsole (see (1)), is a useful derivative for GC/MS analysis. Its mass spectrum is simple with molecular ion peaks at m/z 290/292 and the base peak at m/z 229 due to the loss of the 2-chlorovinyl group (30). 

The reaction product of arsenic trichloride (see Table 1) with 3,4-dimercaptotoluene, 2-chloro-5-methyl-l,3,2-benzodithiarsole, still contains an active chlorine atom, rendering its determination by GC/MS difficult. The derivatization reaction can also be carried out with 2-chlorovinylarsenic oxide (lewisite oxide, CAS 3088-37-7), which is one of the degradation products of lewisite 1. Thus, the highly reactive arsenous compounds can be detected as less reactive derivatives amenable to GC/MS. 

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). 

W.K. Fowler, D.C. Stewart, D.S. Weinberg and E.W. Sarver, Gas chromatographic determination of the lewisite hydrolysate, 2-chlorovinylarsonous... 

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). 

The subcommittee determined that the Army s interim RfDs for GA, GB, GD, and sulfur mustard were scientifically valid but concluded that the RfDs for VX and lewisite and the SF for sulfur mustard were too high. The bases for those conclusions are described below. Research recommendations for filling major data gaps are also presented. 

The subcommittee believes the potential enviromnental and metabolic breakdown products of lewisite are not well identified. There is a possibihty that inorganic arsenic and perhaps even vinyl chloride, two known carcinogens, may be break down products. Accordingly, the subcommittee recommends that the environmental degradation and metabolic products of lewisite be determined, and, if those breakdown products are found to be produced, that the carcinogenic potential of those substances, as well as lewisite, be considered in future assessments. 

Eldridge (1923) conducted tests on human volunteers to assess the effects of dermal exposure to lewisite vapor. The arms of men (one to seven men with previously determined average sensitivity to lewisite) were exposed to varying concentrations of lewisite vapor for periods ranging from... 

As lewisite is a vesicant, emesis is not recommended in those species that can vomit (dogs, cats, swine, and ferrets). Dilution with milk or water is recommended. Activated charcoal is not recommended as severe irritation/vesication of the esophagus or gastrointestinal tract is likely to occur. Endoscopy can be performed very carefully to determine the extent of injury. Esophageal perforation and/or stricture formation may occur. 

Lewisite has the potential to cause skin lesions in any species but the risk is greatest in hairless animals such as pigs, and decreases in fur-covered species (Smith, 1997). Mice and rats appear to be almost twice as susceptible to dermal lewisite exposures than humans (LD50 equals 12,15, and 30 mg/kg, respectively) (DeRosa et al, 2002 RTECS, 2008 Sidell et al, 1997). More studies are needed to determine if rodents would be good sentinel animals. 

Precise data, i.e. a diffusion coefficient expressing the p.c. absorption of lewisite (amount absorbed per area and time), are not available. However, Inns and Rice (1993) conducted p.c. toxicity studies in rabbits and determined the LD50 at 5.3mg/kg (3.5-8.5 mg/kg, 95% confidence interval). The exposed area was 2 cm and exposure lasted for 6 h. 

Inns et al. (1990) had also determined the LD50 of i.v. lewisite administration at 1.8 mg/kg (1.6-2.1 mg/kg 95% confidence interval). Thus, it can be concluded that by exposing 2 cm of rabbit skin to a dose of 5.3 mg/kg for 6 h, a dose producing the equivalent effect of 1.8 mg/kg is absorbed. No further calculations that might exaggerate the reliabihty of available data shall be conducted here. 

Snider et al. (1990) determined the elimination of lewisite from rabbits after p.c. injection. Half-life was determined, ranging from 55 to 75 h. A clearance of 120ml/h/kg was found. However, these findings only describe the overall elimination of arsenic from the organism, following a lewisite exposure. 

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. 

Hanaoka, S., Nomura, K., Wada, T. (2006). Determination of mustard and lewisite related compounds in abandoned chemical weapons (yellow shells) from sources in China and Japan. J. Chromatogr. A 1101 268-77. 

Potentiometric titration and colorimetric methods have been described for the determination of )5-chlorovinyldichloroarsine (Lewisite) . In the latter the organic arsenic is mineralized by refluxing with aqueous sodium hydrogen carbonate and then oxidized to... 

As(V) by the addition of aqueous iodine, followed by conversion to molybdoarsenate and reduction to molybdenum blue by boiling under reflux with a sulphuric acid solution of ammonium vanadate and hydrazine sulphate. The method is sufficiently sensitive to determine down to 3 fig of Lewisite per millilitre of sample. 

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