Mustard gas

Mustard gas or sulfur mustard are names commonly used for the organosulfur chemical compound bis sulfide, which has the chemical structure S₂, as well as other species. In the wider sense, compounds with the substituents are known as sulfur mustards or nitrogen mustards, respectively, where X = Cl or Br. Such compounds are potent alkylating agents, making mustard gas acutely and severely toxic. Mustard gas is a carcinogen. There is no preventive agent against mustard gas, with protection depending entirely on skin and airways protection, and no antidote exists for mustard poisoning.
Also known as mustard agents, this family of compounds comprises infamous cytotoxins and blister agents with a long history of use as chemical weapons. The name mustard gas is technically incorrect; the substances, when dispersed, are often not gases but a fine mist of liquid droplets that can be readily absorbed through the skin and by inhalation. The skin can be affected by contact with either the liquid or vapor. The rate of penetration into skin is proportional to dose, temperature and humidity.
Sulfur mustards are viscous liquids at room temperature and have an odor resembling mustard plants, garlic, or horseradish, hence the name. When pure, they are colorless, but when used in impure forms, such as in warfare, they are usually yellow-brown. Mustard gases form blisters on exposed skin and in the lungs, often resulting in prolonged illness ending in death.

Etymology

The name of mustard gas derived from its yellow color, smell of mustard, and burning sensation on eyes. The term was first used in 1917 during World War I when Germans used the poison in combat.

History as chemical weapons

Sulfur mustard is a type of chemical warfare agent. As a chemical weapon, mustard gas has been used in several armed conflicts since World War I, including the Iran–Iraq War, resulting in more than 100,000 casualties. Sulfur-based and nitrogen-based mustard agents are regulated under Schedule 1 of the 1993 Chemical Weapons Convention, as substances with few uses other than in chemical warfare. Mustard agents can be deployed by means of artillery shells, aerial bombs, rockets, or by spraying from aircraft.

Adverse health effects

Mustard gases have powerful blistering effects on victims. They are also carcinogenic and mutagenic alkylating agents. Their high lipophilicity accelerates their absorption into the body. Because mustard agents often do not elicit immediate symptoms, contaminated areas may appear normal. Within 24 hours of exposure, victims experience intense itching and skin irritation. If this irritation goes untreated, blisters filled with pus can form wherever the agent contacted the skin. As chemical burns, these are severely debilitating. Mustard gas can have the effect of turning a patient's skin different colors due to melanogenesis.
If the victim's eyes were exposed, then they become sore, starting with conjunctivitis, after which the eyelids swell, resulting in temporary blindness. Extreme ocular exposure to mustard gas vapors may result in corneal ulceration, anterior chamber scarring, and neovascularization. In these severe and infrequent cases, corneal transplantation has been used as a treatment. If inhaled in high concentrations, mustard agents cause bleeding and blistering within the respiratory system, damaging mucous membranes and causing pulmonary edema. Depending on the level of contamination, mustard agent burns can vary between first and second degree burns. They can also be as severe, disfiguring, and dangerous as third degree burns. Some 80% of sulfur mustard in contact with the skin evaporates, while 10% stays in the skin and 10% is absorbed and circulated in the blood.
The carcinogenic and mutagenic effects of exposure to mustard gas increase the risk of developing cancer later in life. In a study of patients 25 years after wartime exposure to chemical weaponry, c-DNA microarray profiling indicated that 122 genes were significantly mutated in the lungs and airways of mustard gas victims. Those genes all correspond to functions commonly affected by mustard gas exposure, including apoptosis, inflammation, and stress responses. The long-term ocular complications include burning, tearing, itching, photophobia, presbyopia, pain, and foreign-body sensations.
Symptoms of exposure have been extensively documented. There is a considerable amount of information about the effects of exposure to sulfur mustard in humans and animals from the last century from wartime exposures and laboratory testing. Substantial information in the original documents is not readily available. There are numerous reviews of the literature that include early data as well as recent information.

Medical management

In a rinse-wipe-rinse sequence, skin is decontaminated of mustard gas by washing with liquid soap and water, or an absorbent powder. The eyes should be thoroughly rinsed using saline or clean water. A topical analgesic is used to relieve skin pain during decontamination. For skin lesions, topical treatments, such as calamine lotion, steroids, and oral antihistamines are used to relieve itching. Larger blisters are irrigated repeatedly with saline or soapy water, then treated with an antibiotic and petroleum gauze.
Mustard agent burns do not heal quickly and present a risk of sepsis caused by pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. The mechanisms behind mustard gas's effect on endothelial cells are still being studied, but recent studies have shown that high levels of exposure can induce high rates of both necrosis and apoptosis. In vitro tests have shown that at low concentrations of mustard gas, where apoptosis is the predominant result of exposure, pretreatment with 50 mM N-acetyl-L-cysteine was able to decrease the rate of apoptosis. NAC protects actin filaments from reorganization by mustard gas, demonstrating that actin filaments play a large role in the severe burns observed in victims.
A British nurse treating soldiers with mustard agent burns during World War I commented:

Mechanism of cellular toxicity

Sulfur mustards readily eliminate chloride ions by intramolecular nucleophilic substitution to form cyclic sulfonium ions. These very reactive intermediates tend to permanently alkylate nucleotides in DNA strands, which can prevent cellular division, leading to programmed cell death. Alternatively, if cell death is not immediate, the damaged DNA can lead to the development of cancer. Oxidative stress is another pathology involved in mustard gas toxicity.
Various compounds with the structural subgroup BC₂H₄X, where X is any leaving group and B is a Lewis base, have a common name of mustard. Such compounds can form cyclic "onium" ions that are good alkylating agents. These compounds include bisethers, the amines, and sesquimustard, which has two α-chloroethyl thioether groups connected by an ethylene bridge. These compounds have a similar ability to alkylate DNA, but their physical properties vary.

Formulations

In its history, various types and mixtures of mustard gas have been employed. These include:

H – Also known as HS or Levinstein mustard. This is named after the inventor of the "quick but dirty" Levinstein Process for manufacture, reacting dry ethylene with disulfur dichloride under controlled conditions. Undistilled mustard gas contains 20–30% impurities, which means it does not store as well as HD. Also, as it decomposes, it increases in vapor pressure, making the munition it is contained in likely to split, especially along a seam, releasing the agent to the atmosphere.
HD – Codenamed Pyro by the British, and Distilled Mustard by the US. Distilled mustard of 95% or higher purity. The term "mustard gas" usually refers to this variety of mustard.
HT – Codenamed Runcol by the British, and Mustard T- mixture by the US. A mixture of 60% HD mustard and 40% O-mustard, a related vesicant with lower freezing point, lower volatility and similar vesicant characteristics.
HL – A blend of distilled mustard and lewisite, originally intended for use in winter conditions due to its lower freezing point compared to the pure substances. The lewisite component of HL was used as a form of antifreeze.
HQ – A blend of distilled mustard and sesquimustard.
Yellow Cross – any of several blends containing sulfur mustard. Named for the yellow cross painted on artillery shells.
Commonly-stockpiled mustard agents (class)

History

Development

Mustard gases were possibly developed as early as 1822 by César-Mansuète Despretz. Despretz described the reaction of sulfur dichloride and ethylene but never made mention of any irritating properties of the reaction product. In 1854, another French chemist, Alfred Riche, repeated this procedure, also without describing any adverse physiological properties. In 1860, the British scientist Frederick Guthrie synthesized and characterized the mustard agent compound and noted its irritating properties, especially in tasting. Also in 1860, chemist Albert Niemann, known as a pioneer in cocaine chemistry, repeated the reaction, and recorded blister-forming properties. In 1886, Viktor Meyer published a paper describing a synthesis that produced good yields. He combined 2-chloroethanol with aqueous potassium sulfide, and then treated the resulting thiodiglycol with phosphorus trichloride. The purity of this compound was much higher and consequently the adverse health effects upon exposure were much more severe. These symptoms presented themselves in his assistant, and in order to rule out the possibility that his assistant was suffering from a mental illness, Meyer had this compound tested on laboratory rabbits, most of which died. In 1913, the English chemist Hans Thacher Clarke replaced the phosphorus trichloride with hydrochloric acid in Meyer's formulation while working with Emil Fischer in Berlin. Clarke was hospitalized for two months for burns after one of his flasks broke. According to Meyer, Fischer's report on this accident to the German Chemical Society sent the German Empire on the road to chemical weapons.
The German Empire during World War I relied on the Meyer-Clarke method because 2-chloroethanol was readily available from the German dye industry of that time.