Sulfur mustard damages

In the case of sulfur mustard, analysis of low molecular weight urinary metabolites suffers from the same drawback as in the case of anticholinesterases, i.e., these products are rapidly excreted and provide therefore limited retrospectivity. Similarly, the in vivo lifetime of DNA adducts of sulfur mustard are less than those of protein adducts due to repair of DNA damage. 

Sulfur mustard (HD) is a chemical vesicant capable of causing severe skin and eye damage at very low concentrations. The chemical name, synonyms, identification codes, molecular formula and structural formula for this agent are as follows ... 

Acute exposures to sulfur mustard can result in skin and eye damage, gastrointestinal irritation, and depressed myelopoiesis (resulting in leukopenia and anemia) (Vogt et al., 1984). Damage to the respiratory tract, which is the principal cause of mortality in the first few days to weeks after exposure to sulfur mustard, involves acute edema, inflammation, and destruction of the airway epithelial lining (Institute of Medicine, 1993). Infection of the respiratory tract resulting in bronchopneumonia is a common complication of exposure to sulfur mustard. 

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. 

In the review by Papirmeister et al. (1991), it was noted that sulfur mustard-induced cytotoxicity is dose dependent and that DNA appeared to be more sensitive to mustard-induced alkylation than are other cellular constituents. The low-dose effects of sulfur mustard are characterized by gen-otoxicity and inhibition of mitosis. The loss of cellular reproduction may be due to bifunctional alkylation that ultimately prevents normal DNA replication. It was hypothesized that monofunctional DNA damage might be responsible for low-dose mutagenic and possibly carcinogenic effects. 

Sulfur mustard is a blistering or vesicating agent that primarily incurs damage at the organs that come into immediate contact with either its liquid or vaporous form. However, severe dermal and respiratory exposure to the agent may also result in the absorption of sulfur mustard that subsequently causes additional systemic damage (Kehe and Szinicz, 2005). 

Figure 50.4 depicts the basic chemical mechanism by which sulfur mustard incurs the primary damage to biological molecules which results in subsequent damage to cells, tissues, and organs. 

Bhat, K.R., Benton, B.J., Ray, R. (2006). Poly (ADP-rihose) polymerase (PARP) is essential for sulfur mustard-induced DNA damage repair, hut has no role in DNA ligase activation. J. Appl. Toxicol. 26 452-7. 

Calvet, J.H., Coste, A., Levame, M., Harf, A., Macquin-Mavier, I., Escudier, E. (1996). Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of glucocorticoids. Hum. Exp. Toxicol. 15 964-71. 

Similar to bleach s oxidative iodine properties, topical povidone-iodine at 15 and 30 min post-exposure to sulfur mustard exhibited protective effects. Severity of the dermal parameters, acute inflammation and dermal necrosis was significantly reduced, and reduced skin damage was observed in areas adjacent to treated sites (Brodsky and Wormser, 2007). 

Toxic effects of sulfur mustard and ethyleneimine on animals were described in the 19th century. The powerful vesicant action of sulfur mustard led to its u.se in World War I. and medical examination of the victims revealed that tissues were damaged at sites distant from the area of contact." Such systemic elTects included leukopenia, bone marrow aplasia, lymphoid tissue suppression, and ulceration of the gastrointestinal tract. Sulfur mustard was shown to be active against animal tumors, but it was too nonspecific for clinical use. A variety of nitrogen mustards were synthesized between the two world wars. Some of these compounds (e.g.. 

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