Mustard toxicity

There is no antidote for nitrogen mustard toxicity, and decontamination of potentially exposed persons must be done within minutes to avoid tissue damage. Victims should be moved out of the hot zone, administered oxygen and/or assisted ventilation, and seek medical attention at once. The nitrogen mustards are delayed chemical agents, and may delay for up to twenty-four hours to show symptoms. They are poisons, and contact with vapor or liquids can be fatal. Do not eat, drink, or smoke during response to a nitrogen mustard incident or criminal event. 

Caution There is no antidote for nitrogen mustard toxicity decontamination of all potentially exposed areas within minutes after exposure is the only effective method to decrease tissue damage. Other than that, treatment is mainly supportive. 

The mechanism of action of sulfur mustard is multifaceted and complex, and has been reviewed in some detail by Papirmeister et al. (1991), Hurst and Smith (2008), and Smith et al. (2008). Efforts to understand the mechanisms of sulfur mustard toxicity are ongoing. Basically, sulfur mustard disrupts the interface of the epidermis and basement membrane causing blistering between the epidermis and dermis. Both immediate (immediate cell membrane damage) and delayed phases (secondary effects resulting from inflammatory responses, DNA damage, vascular leakage) have been described for sulfur mustard-induced dermal effects (Somani and Babu, 1989). Many of the toxic effects of sulfur mustard can be attributed to oxidative stress. 

Among the most studied mechanisms of sulfur mustard toxicity are thiol depletion resulting in intracellular calcium... 

Medical management of nitrogen mustard exposure is similar to that for sulfur mustard and involves prevention of exposure and, where exposure has occurred, decontamination and support therapy. The use of antioxidants in the treatment of nitrogen mustard toxicity is currently under investigation (Hardej and Billack, 2006). 

Petrali, J., Miskena, F., Hamilton, T., Finger, A., Janny, S. (1997). Sulfur mustard toxicity of the rabbit eye an ultrastructural study. J. Toxicol. Cutan. Ocul. Toxicol. 16(4) 221-il. 

Smith, W.J., Gross, C.L., Chan, P., Meier, H.L. (1990). The use of human epidermal keratinocytes in cultures as a model for studying sulfur mustard toxicity. Cell Biol. Toxicol. 6 285-91. 

Korkmaz, A., Yaren, H., Topal, T., Oter, S. (2006). Molecular targets against mustard toxicity implication of cell surface receptors, peroxynitrite production and PARP activation. Arch. Toxicol. 80 662-70. 

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. 

Debiak, M., Kehe, K., Burkle, A. (2008). Role of poly(ADP-ribose) polymerase in sulfur mustard toxicity. Toxicology (June 18, Epub ahead of print) doi 10.1016/j.tox.2008.06.002. 

Ray, R., Majerus, B.J., Munavalli, G.S., Petrali, J.P. (1993). Sulfur mustard-induced increase in intracellular calcium a mechanism of mustard toxicity. Proceedings of the U.S. Army Medical Bioscience Review, pp. 267-76. 

Riviere, J.E., Monteiro-Riviere, N.A., Inman, A.O. (1997). The effect of altered media flow and glucose concentration on sulfur mustard toxicity in the isolated perfused porcine skin flap. In Vitro Toxicol. 10 169-81. 

Simbulan-Rosenthal, C.M., Ray, R. et al. (2006). Calmodulin mediates sulfur mustard toxicity in human keratmoc des. 

Medical Countermeasures and Other Therapeutic Strategies for Sulfur Mustard Toxicity... 

Amir, A., Chapman, S., Kadar, T., Gozes, Y., Sahar, R., Allon, N. (2000h). Sulfur mustard toxicity in macrophages effect of dexamethasone. J. Appl Toxicol 20 S51-8. 

Bhattacharya, R., Lakshmana Rao, P.V., Pant, S.C., Pravin Kumar, Tulsawani, R.K., Pathak, U., Kulkami, A., Vijayar-aghavan, R. (2001). Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo. Toxicol. Appl. Pharmacol. 176 24-33. 

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

Paromov, V., Suntres, Z., Smith, M., Stone, W.L. (2007). Sulfur mustard toxicity following dermal exposure role of oxidative stress, and antioxidant therapy. J. Burns Wounds 1 7. 

Pathak, U., Raza, S.K., Kulkami, A.S., Vijayaraghavan, R., Kumar, P., Jiaswal, D.K. (2004). Novel S-substituted amino-alkylamino ethanethiols potential antidotes against sulfur mustard toxicity. J. Med. Chem 47 3817-22. 

Ray, R., Benton, B.J., Anderson, D.R., Byers, S.L., Petrali, J.P. (2000). Intervention of sulfur mustard toxicity by down-regulation of cell proliferation and metabolic rates. J. Appl. 

Sawyer, T.W. (1998b). Modulation of sulfur mustard toxicity by arginine analogues and related nitric oxide synthase inhibitors in vitro. Toxicol. Sci. 46 112-23. 

Sawyer, T.W., Risk, D. (2000). Effects of selected arginine analogues on sulphur mustard toxicity in human and hairless guinea pig skin keratinoc des. Toxicol. Appl. Pharmacol. 163 75-85. 

Simbulan-Rosenthal, C.M., Ray, R., Benton, B., Soeda, E., Daher, A, Anderson, D., Smith, W.J., Rosenthal, D.S. (2006). Calmodulin mediates sulfur mustard toxicity in human kera-tinocytes. Toxicology 227 21-35. 

The second exception is that while an antidote is available for systemic effects of Lewisite exposure, there are no antidotes for nitrogen mustard or sulfur mustard toxicity, with one minor caveat if given within minutes after exposure, intravenous sodium thiosulfate may prevent death due to sulfur mustard exposure (25). Otherwise, the medical management for skin, ocular, and respiratory exposure is only supportive. One guideline physicians can follow is to keep skin, eye, and airway lesions free from infection. 

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