Toxicity sulphur mustard

Andrew, D.J., Lindsay, C.D. (1998). Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by glutathione esters. Hum. Exp. Toxicol. 17 387-95. 

Kumar, O., Sugendran, K., Vijayaraghavan, R. (2001). Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes. Chem. Biol. Interact. 134 1-12. 

Sawyer, T.W., Risk, D. (1999). Effect of lowered temperature on the toxicity of sulphur mustard in vitro and in vivo. Toxicology 134 27-37. 

Gautam, A., Singh, S., Kulkami, A.S., Pant, S.C., Vijayaraghavan, R. (2005). Protective effect of Aloe vera L. gel against sulphur mustard induced systemic toxicity and skin lesions. Indian J. Pharmacol. 37 103-10. 

Han, S., Espinoza, L.A., Liao, H., Boulares, A.H., Smulson, M.E. (2004). Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analogue 2-chloroethylethyl sulphide (GEES) in Jurkat T cells and normal human lymphocytes. Br. J. Pharmacol. 141 795-802. 

Mi, L., Gong, W., Nelson, P., Martin, L., Sawyer, T.W. (2003). Hypothermia reduces sulphur mustard toxicity. Toxicol. Appl. Pharmacol. 193 73-83. 

Sawyer, T.W., Lundy, P.M., Weiss, M.T. (1996). Protective effect of an inhibitor of nitric oxide synthase on sulphur mustard toxicity in vitro. Toxicol. Appl. Pharmacol. 141 138 4. 

Vijayaraghavan, R., Kumar, P., Joshi, U., Raza, S.K., Lakshmana Rao, P.V., Malhotra, R.C., Jaiswal, D.K. (2001a). Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity. Toxicology 163 83-91. 

Vijayaraghavan, R., Kumar, P., Dubey, D.K., Ram Singh, Sachan, A.S., Deo Kumar, Sugendran, K., Om Kumar, Singh, M., Pant, S.C., Bhattacharya, R. (2002). Acute toxicity studies of CC2 an effective chemical decontaminant of sulphur mustard in hydrophilic formulation. Ind. J. Pharmacol. 34 321-31. 

This idea that the toxicity of sulphur mustard could be enhanced by the presence of particles was put forward again during the Iran-Iraq war, when chemical weapons were used on a large scale, and again in the Gulf War, when chemical weapons were not used. The concept is worth considering in some detail. 

It was pointed out in Chapter 2 that the toxicity of chemical warfare agents should not be judged simply in terms of the doses or exposures necessary to cause death. Sulphur mustard is an effective incapacitating agent indeed its value in World War I rested on this property. 

Prentiss (1937) gave the following figures for the toxicity of sulphur mustard ... 

The work reported by Connors et al. (1964) followed work done at CDE by Callaway and Pearce, reported in 1958. They investigated the effects of thiosulphatcUrisodium citrate mixtures (10 1, 2.75 g kg-1, IP) on the toxicity of sulphur mustard in rats. The combination was referred to as Thiocit and it was demonstrated that ... 

In 1986, Vojvodic and colleagues reported a study of the protective effects of a number of compounds and combinations of compounds on the toxicity of nitrogen and sulphur mustards (Vojvodic et al., 1986). Protective indices similar to those obtained by Callaway and Pearce (1958) were reported. Work on the value of thiosulphate in the treatment of mustard gas poisoning has also been reported by Fasth and Sorbo (1973). Sodium thiosulphate has been recommended as a local treatment for accidentally extravasated doses of nitrogen mustards (Dorr et al., 1988). 

The majority of substances listed on Schedule 1 of the Chemical Weapons Convention are considered to be percutaneous hazards (OPCW, 1993). In particular, sulphur mustard (HD) and VX are the most extensively studied agents of this genre and are representative of chemical warfare agents that exhibit mainly local or systemic percutaneous toxicity, respectively (Table 1). 

Mustard gas slowly hydrolyses in water and forms hydrochloric acid and thiodiglycol. Both final products of the hydrolysis are non-toxic. The hydrolysis is dependent on temperature, density, viscosity, pH value and pressure. Because mustard gas is relatively insoluble, the slower dissolving process is the main factor of interest here. There is a huge difference between distilled water and normal sea water. In distilled water the half-life is 8.5 minutes at 25oC, while for salt water at the same temperature the half-life is 60 minutes. For sea water the hydrolysis will be slowed down by a factor of more than 3 times. The pace of hydrolysis of sulphur mustard gas also depends on the content of salt (cations and anions) in an aqueous solution. The reported half-life of sulphur mustard gas in sea-water is 15 minutes at 25oC, 49 minutes at 15oC, and 175 minutes at 5oC. ... 

Nitrogen mustards, in general, react slower than the sulphur mustards. The hydrolysis of nitrogen mustards was extensively studied recently. " The products of hydrolysis are non-toxic. The solubility in water for HN-3 is 0.16 g. The time frame for a total decomposition in fresh water is approximately 3 weeks. For the tertiary amine, HN-1, the solubility in water is much higher. 

Diphenylchloroarsine (DA), and diphenylcyanoarsine (DC), which both contain arsenic and are in the form of a powder at ambient temperatures, were used as mask breakers during WWI. The particles were able to penetrate the filters used at the time and could induce a soldier to break the seal of his mask allowing a more toxic agent such as phosgene to take effect. Diphenylchloroarsine and diphenylcyanoarsine were also mixed with sulphur mustard to lower the freezing temperature of the mustard. 

Whilst the majority of the recovered munitions are of WWII origin, a significant number stem from WWI and the inter-war years. They include shells, mortars and grenades of various types filled with a range of toxic chemical substances, including arsenious chloride, chloropicrin (trichloronitromethane), KSK (ethyl iodoacetate), phosgene (carbonyl chloride), and thickened and un-thickened sulphur mustard (principally bis 2,2 dichloroethyl sulphide). When found, the munitions are normally heavily corroded and often little, if any, indication of their probable contents remains. 

---