**1. Introduction**

#### **1.1. History**

The exact date of the first sulfur mustard synthesis is somewhat unclear, but the first report by Despretz may have been in 1822. An 1860 report by Neimann described a delayed-effect vesicant oil as a reaction product of ethylene on a mixture of sulfur chlorides. In 1886, a process to produce significant quantities of pure sulfur mustard was described by Meyer using sodium sulfide, ethylene chlorohydrin, and hydrochloric gas [1, 2].

Mustard gas was used for the first time by German forces against Allied troops in July 12, 1917 that caused more than 2100 casualties. The Allies began using mustard gas against German troops in 1918. During 1935–1936, the Italian army dropped mustard-gas bombs in Ethiopia to destroy Emperor Haile Selassie's army. During 1963–1967, Egypt used mustard gas and a

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nerve agent in Yemen to support a coup against the Yemeni monarchy. During the Iran-Iraq war (1980–1988), Iraq used chemical weapons, including tabun and mustard gas, against Iran and Iraq's Kurdish minority. Iraq's use of chemical weapons was confirmed by the United Nations experts [3].

severely wounded [6, 13]. A wide range of late ocular involvements have been reported, which include chronic blepharitis, dry eye, conjunctival vessel tortuosity, limbal ischemia and stem cell deficiency, corneal scarring and neovascularization, corneal thinning and perforation, epithelial irregularity, recurrent or persistent epithelial defects, and secondary degenerative changes

Corneal Blindness Caused by Mustard Gas http://dx.doi.org/10.5772/intechopen.70469 5

Dry eye is a late ocular complication of exposure to mustard gas, the symptoms of which are often severe and persistent and can influence many aspects of intoxicated victims' lives [5, 6, 18, 19]. Although the exact pathophysiologic cause of dry eye syndrome after exposure to mustard gas is not known yet, most studies in this regard have revealed evidence for increased apoptosis in the conjunctival epithelium [20]. This apoptosis also occurs in goblet cells resulting in a significant decrease in goblet cell density thus reducing mucin production and tear film stability [20]. Additionally, dysfunction of lacrimal glands may occur secondary

Mustard gas-related corneal involvements are completely different from those observed in other causes of corneal opacities that develop after trauma, infection, and acid or alkaline burns [18]. For example, corneal thinning and fragility is a striking feature in mustard gas-induced ocular injuries [18]. Such differences can be explained by the presence of other concomitant abnormalities such as limbal ischemia and vascular abnormalities [18]. Limbal ischemia causes scleral and corneal thinning, and the presence of leaking limbal vessels results in the accumulation of abnormal materials such as lipid and amyloid in the adjacent cornea [12]. Alterations of corneal stroma secondary to acute and chronic inflammation, stromal scar and fibrosis, and deposits make stromal layers too rigid to be separated by air. Therefore, deep anterior lamellar keratoplasty using the big-bubble technique is hard to perform in mus-

**Figure 1.** Abnormalities of the cornea, including surface irregularity, thinning, and intrastromal lipid and amyloid

deposits, are evident in an eye suffering from mustard gas keratitis.

including lipid/amyloid deposits (**Figure 1**) [5, 6, 12–17].

to lymphocytic infiltration of the glands [20].

tard gas-induced keratitis [12].

#### **1.2. Molecular formula of mustard gas and its biochemical mechanism of tissue injury**

Sulfur mustard (C<sup>4</sup> H8 Cl2 S) is one of a class of chemical warfare agents which are known as vesicants because they cause vesicles, or blisters, on exposed skin. Pure sulfur mustard is odorless, colorless, and viscous liquid at room temperature. It is usually yellow-brown in color and has an odor resembling garlic, horseradish, or mustard plants when used as warfare agents, which is how it got its name. However, this compound has absolutely no relation whatsoever to culinary mustard [4].

Mustard gas is a lipophilic, highly cytotoxic agent that rapidly penetrates tissue [5]. Exposed skin surfaces, eyes, the linings of both respiratory and gastrointestinal tracts, and renal systems as well as the bone marrow are all at risk. The risks increase dramatically under hot, humid conditions, and it can be lethal at sufficiently high doses [5, 6]. It has been demonstrated that 80% of sulfur mustard applied to the skin evaporates, 10% remains in the skin, and 10% gets absorbed systemically [7]. Susceptibility of the eyes to the toxic effects of mustard gas is due to moistness of the ocular surface, allowing activation of the agent. Additionally, corneal epithelial cells have a high turnover and metabolic rate that increase their vulnerability to the lipophilic sulfur mustard trapped into the oily tear layer [8].

Sulfur mustard is a cellular poison that triggers apoptosis as a cytotoxic mechanism. The acute toxic effects of mustard vesicants are usually attributed to the consequences of alkylation reactions with organic compounds including nucleoproteins such as DNA [9]. The ladder pattern of DNA fragmentation after cell exposure to mustard gas indicates internucleosomal cleavage of DNA. Alkylation reactions can result in genotoxic effects as well as physiological and metabolic disturbances that induce apoptosis [10]. In addition, mustard gas is a mutagen and is a known carcinogen that is associated with an increased risk of developing lung and other respiratory tract cancers [11].
