Practice Essentials
Mustard agents are vesicants (blistering agents) used in warfare to produce casualties, deny access to areas on the battlefield, and slow down enemy movement by forcing troops to wear full protective equipment. Mustard agents are alkylating compounds that cause damage to the eyes, skin, and respiratory tract. There are different types of mustard agents, including sulfur mustard (H, HD, HT), nitrogen mustards (Hn-1, Hn-2, Hn-3), and mustard-lewisite (HL). Sulfur mustard is used as a chemical weapon, while nitrogen mustard is used as a chemotherapeutic agent.
Several properties of mustard agents make them ideal for battlefield use. Mustard is heavier than air and will accumulate in low-lying areas. Temperature affects volatility, with higher temperature aerosolizing mustard making it more deadly. Mustard agents rapidly penetrate skin and clothing. Full protective gear is required to protect soldiers or responders from injury.
Mustard agents are oily liquids ranging from colorless in a pure state to yellowish/brown when impurities are present. The smell associated with these agents has been described as that of mustard, garlic, or horseradish. The odor should not be relied upon for detection, due to olfactory fatigue and variability in the human olfactory sense.
Injury from mustard exposure follows a latency period with effects occurring in a delayed fashion. The eyes are the most sensitive to mustard exposure and exhibit effects earliest. Mustard exposure to the skin leads to blister and bullae formation. Inhalation of mustard vapors causes respiratory tract irritation and inflammation. Decontamination must occur immediately after exposure to prevent injury.
Mustard agents throughout the world are in the process of being destroyed, following the ratification of the Chemical Weapons Convention. However, there are conflicting data on the status of this effort. [1] Most recent exposures are due to the handling of old ordinance.
The United States successfully completed the destruction of nearly 90% of its original chemical weapons stockpile in January 2012. The original stockpile in Colorado consisted of 2,613 US tons of the mustard agents HD and HT configured in projectiles and mortar rounds. The original stockpile in Kentucky comprised 523 US tons of nerve and mustard agents in rockets and projectiles, with approximately 90 tons of that quantity consisting of mustard agent H in projectiles. [2]
Operations are on target for completion by the Chemical Weapons Convention treat commitment of September 30, 2023. The first two campaigns are complete. The remaining 4.2-inch mortar round campaign is expected to end by the Chemical Weapons Convention treaty commitment of September 30, 2023. US public law mandates stockpile destruction by December 31, 2023. [2]
Despite ongoing destruction of US stockpiles, the chemical threat from sulfur mustard remains, due to the low cost and availability of these agents.
For patient education information, see Chemical Warfare and Personal Protective Equipment.
Background
Sulfur mustard was first produced in 1822 but was not deployed on the battlefield until the First World War (WWI). During the Battle of Ypres, Belgium in July 1917, Germany was the first nation to deploy sulfur mustard-containing artillery shells on the battlefield against British and Canadian troops. The Allied Powers in WWI referred to this agent as HS (Hun Stoffe), later shortened to H. Pure distilled sulfur mustard was given the name HD (Distilled Hun). Other names included yellow cross (how it was identified on artillery shells), Yperite (after the location of first use), S-LOST (from Lommel and Steinkopf, German chemists who developed mass production of mustard), or Kampfstaff LOST (Kampfstaff = warfare agent).
Mustard holds the title “King of the War Gases” due to the large number of casualties that it inflicted. This name is somewhat of a misnomer as mustard is an aerosol, not a gas. It is primarily used as an area-denial tool and to incapacitate troops. [3, 4]
Use of mustard agents continued after WWI. During the 1930s, Italy dropped mustard-containing bombs and sprayed mustard from aircraft during its invasion of Ethiopia and Japan employed mustard during its invasion of China. During WWII, both Allied and Axis powers produced significant amounts of mustard, including nitrogen mustard (Hn), but it was never used on the battlefield. [3] A significant mustard release occurred in 1943 when German bombers struck an American munitions vessel carrying mustard in the Italian port of Bari, resulting in 617 casualties and 83 fatalities from mustard released into the air and water. [5]
Since WWII, the Middle East has been the primary location for use of mustard agents. Egypt used mustard against royalist forces during the Yemen Civil War (1963-1967). [3] During the Iran-Iraq War (1980-1988), Iraq deployed mustard against Iranian troops and civilian targets, generating a large number of casualties. [6] More recently, in 2015 and 2016, mustard agents have been used by both Syria and nonstate actors (ISIS) as part of the ongoing Syrian civil war. [7, 8, 9, 10]
In April 1997, the US ratified the Chemical Weapons Convention (CWC). Part of this treaty involves the destruction of US stockpiles of chemical and nerve agents, including mustard. Exposures to mustard still occur, largely due to accidental contact with discarded munitions or during disarming operations. [11, 12, 13] Destruction of the US mustard stockpile is ongoing. [14]
Pathophysiology
Despite being referred to as gas, mustard agents are liquids at room temperature. Pure mustard is clear and odorless, while mustard with impurities is generally a yellow/brown oily liquid. The impurities give these agents the odor of mustard, garlic, or horseradish. [15]
Persistence in the environment and level of vaporization depend on temperature. In more temperate climates, mustard agents vaporize slowly and may persist for a week. In desert climates, they vaporize rapidly and may persist for a day or more, depending on the extent of exposure. Rapid vaporization makes mustard more deadly in warmer climates. [16] Mustard has a high freezing point (57°F) and must be mixed with other substances to lower its freezing point for use in winter environments. [4] Sulfur mustard is 5.4 times heavier than air, leading to accumulation in low-lying area, which made it suitable for attacking trenches. [4, 16]
Mustard agents cause damage through multiple proposed mechanisms. Mustard agents are lipophilic and get absorbed rapidly through the skin. Once absorbed, they act primarily as alkylating agents that form highly reactive sulfonium (sulfur mustard) or imonium (nitrogen mustard) ions within minutes of absorption. These ions react with sulfhydryl and amino groups in proteins and DNA. Sulfur mustard alkylates purine bases (guanine and adenine) in DNA. This triggers the activation of cellular repair machinery, rapidly depleting cellular stores of nicotinamide adenine dinucleotide (NAD+). Depletion of NAD+ stores begins around 1 hour after exposure and peaks at 4 hours, leading to indirect inhibition of glycolysis and cellular necrosis. [16, 15, 17] More recent studies indicate that sulfur mustard may also inhibit glycolysis directly. [18]
Another proposed mechanism of mustard agents is a reaction with glutathione, causing its depletion and increasing cellular susceptibility to oxygen–free radical damage. Depletion of glutathione leads to the inactivation of sulfhydryl-containing enzymes, leading to the inability to control calcium homeostasis. Increases in intracellular calcium trigger the activation of cell death machinery, resulting in apoptosis. Depletion of glutathione also leads to lipid peroxidation, with formation of free radicals that damage cell membranes. [4]
Epidemiology
The lethal dose of sulfur mustard in humans varies by route of exposure. The median lethal concentration for inhalation (LCt50) is 1500 mg-min/m3. The medial lethal dose (LD50) is 50mg/kg for cutaneous exposure and 0.7mg/kg for oral exposure. [19] The LD50 for cutaneous nitrogen mustard exposure in humans is 75 mg/kg. [19]
Battlefield concentrations in WWI were estimated to be between 19-33 mg/m3. Exposures at these concentrations for several minutes led to eye and skin injury. Exposures of 30-60 minutes resulted in severe respiratory injury and death. [16] The majority of chemical casualties in WWI were caused by mustard (76-88%), with a mortality rate of 2-3%. [4] Mortality rates in the Iran-Iraq War were 3-4%. [16]
