Sulfur mustards Levels

As part of a study to identify the degradation products of sulfur mustard, bis(2-chloroethyl) sulfide, the behavior of various sulfonium salts towards electrospray ionization mass spectrometry has been investigated. Among the compounds studied was 3 -(2-chloroethyl)pentamethylene sulfonium tetrafluoroborate. The ion was readily detected at the 0.01 M level with no ion fragmentation <1997JMP1247>. 

M.V.S. Suryanarayana, R.K. Shrivastava, D. Pa-ndey, R. vaidyanathaswamy, S. Mahajan and D. Bhoumik, Simple time weighted average level air-monitoring method for sulfur mustard in work places, J. Chromatogr. A, 907, 229-234 (2001). 

Wils et al. (25,26) previously reported an entirely different approach to TDG analysis. TDG in urine was converted back to sulfur mustard by treatment with concentrated HC1. The sample treatment is less straightforward than the methods described above, but analysis as sulfur mustard is facile. Urine, plus 2H8-TDG as internal standard, was cleaned up by elution through two C18 cartridges. Concentrated HC1 was added and the sample stirred and heated at 120 °C. Nitrogen was blown over the solution and sulfur mustard isolated from the headspace by adsorption onto Tenax-TA. The method was used to detect TDG in urine from casualties of CW attacks (see below). A disadvantage of this method is that it may convert metabolites other than TDG to sulfur mustard. This is supported by the detection of relatively high levels of analytes in urine from control subjects. Vycudilik (27) used a similar procedure, but recovered the mustard by steam distillation and extraction. 

An enzyme-linked immunosorbent assay (ELISA) was developed by Van der Schans and colleagues for detection of the mustard adduct within DNA, using monoclonal antibodies raised against N7-HETE-guanosine-5 -phosphate coupled to keyhole limpet hemocyanin (n). The ELISA was successfully applied in toxicokinetic studies in which levels of adducted DNA were followed in conjunction with measurement of intact sulfur mustard (12). 

The ELISA for detection of the DNA adduct was successfully applied to blood samples from two casualties of the Iraq-Iran conflict. These samples were collected 22 and 26 days following the alleged exposure to sulfur mustard (13). Concentrations found in lymphocytes and granulocytes were equivalent to similar levels found in human blood after treatment in vitro with 0.015-0.43 xM sulfur mustard. 

The analytical procedure for S-[2-[(hydroxyethyl) thio]ethyl-Cys-Pro-Phe was successfully applied to blood samples from nine Iranian casualties of the Iraq-Iran war, all exhibiting skin injuries compatible with exposure to sulfur mustard. The blood samples were collected 8-9 days after the alleged exposure and stored at — 70 °C. The albumin adduct was detected in all cases, at levels estimated as corresponding to those after in vitro exposure of human blood to mustard concentrations ranging from 0.4-1.8 xM. 

The Army s interim RfD for sulfur mustard is 7 x 10 mg/kg per day. ORNL (1998) calculated that value on the basis of the lowest oral dose of sulfur mustard that produced forestomach lesions (epithelial acanthosis, which is an increase in the thickness of the stratum spinosum of the epithelial tissue of the forestomach) in rats. The lowest-observed-adverse-effect level (LOAEL) for that effect was 0.03 mg/kg per day in a two-generation reproductive study (Sasser et al. 1989a). In that study, male and female rats were administered sulfur mustard for 5 days per week for 15 weeks, daily for 3 weeks, and 4 days per week for 3 weeks. Because of this discontinuous dosing protocol, ORNL adjusted the LOAEL (LOAELajj) to calculate the doses for continuous exposures. That adjustment was done by calculating the total dose administered during the different exposure protocols ... 

Azizi et al. (1995) investigated changes in serum concentrations of reproductive hormones and sperm counts in men who had been exposed to sulfur mustard during wartime. In 16 individuals, serum free and total testosterone and dehydroepiandrosterone were markedly decreased in the first five weeks after exposure but levels returned to normal by 12 weeks. In 28 of 42 men evaluated one to three years after exposure, sperm counts were less than 30 million ceUs/mL and follicle-stimulating hormone was increased compared to controls having sperm counts above 60 million cells/mL. Testicular biopsy of the test subjects revealed partial or complete arrest of spermatogenesis. 

Watson, A., Opresko, D., Young, R., Hauschild, V. (2006a). Development and application of acute exposure guideline levels (AEGLs) for chemical warfare nerve and sulfur mustard agents. J. Toxicol. Environ. Health, Part B. 9 173-263. 

In addition to the acute toxic effects on the eyes, skin, and respiratory tract, both acute and longer-term neuropsychiatric effects (e.g. depression, anxiety, neurasthenia, insomnia, post-traumatic stress syndrome) have been documented for individuals exposed to sulfur mustard (Romano et al, 2008). Many of these effects have been documented for individuals exposed during noncombat (e.g. munitions plant workers) activities and are not always the result of high-level exposure that result in serious overt effects. Longer-term effects such as chronic bronchitis have been associated with occupational exposures that included episodes of acute toxicity, and delayed or recurrent keratitis may occur 8-40 years after a severe vapor exposure. Sulfur mustard-induced immunosuppression resulting in greater susceptibility to infections has also been reported. 

Results of a multigeneration study in rats given sulfur mustard by gavage showed no significant adverse effects on reproductive parameters at any dose level, but revealed dose-related lesions of the squamous epithelium of the forestomach (acanthosis and hyperplasia). It is likely that the fore stomach lesions were a function of the treatment regimen whereby the bolus dose in an oil vehicle (sesame... 

Various standards and guidelines have been developed for sulfur mustard. These values are applieable to occupational exposures, emergeney planning and response efforts, and remediation efforts. Airborne exposure limits (AELs) and health-based environmental sereening levels (HBESLs) for sulfur mustard have been developed by the US Army (USACHPPM, 1999, 2000). Most health-based criteria for sulfur mustard vapor exposure are based upon protection of the eyes and respiratory traet whieh are the most sensitive targets. 

Acute Exposure Guideline Levels (AEGLs) for sulfur mustard have been developed for emergeney planning and... 

Meier, H., Gross, C., Papirmeister, B. (1987). 2,2 -dichlorodiethyl sulfide (sulfur mustard) decreases NAD levels in human leukocytes. Toxicol. Lett. 39 109-22. 

Mol, M., Van de Rsuitt, A., Kluivers, A. (1989). NAD levels and glucose uptake of cultured human epidermal cells exposed to sulfur mustard. Toxicol. Appl. Pharmacol. 98 159-65. 

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