Mustard gas
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Mustard gas or sulfur mustard is a
chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
belonging to a family of cytotoxic and
blister agent A blister agent (or vesicant), is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affec ...
s known as mustard agents. The name ''mustard gas'' is technically incorrect: the substance, when dispersed, is often not actually a gas, but is instead in the form of a fine mist of liquid droplets.https://www.acs.org/content/dam/acsorg/education/resources/highschool/chemmatters/gc-mustard-gas-personal-safety-and-natl-security.pdf Mustard gases form blisters on exposed skin and in the lungs, often resulting in prolonged illness ending in death. The active ingredient in typical mustard gas is the organosulfur compound bis(2-chloroethyl) sulfide. In the wider sense, compounds with the structural element are known as ''sulfur mustards'' and ''nitrogen mustards'', respectively. Such compounds are potent
alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
s, which can interfere with several biological processes.


History as chemical weapons

As a chemical weapon, mustard gas was first used in
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
, and has been used in several armed conflicts since then, including the
Iran–Iraq War The Iran–Iraq War was an armed conflict between Iran and Iraq that lasted from September 1980 to August 1988. It began with the Iraqi invasion of Iran and lasted for almost eight years, until the acceptance of United Nations Security Counci ...
, resulting in more than 100,000 casualties. Today, 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 (though since then, mustard gas has been found to be useful in cancer
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
). Mustard agents could be deployed by means of artillery shells, aerial bombs,
rocket A rocket (from it, rocchetto, , bobbin/spool) is a vehicle that uses jet propulsion to accelerate without using the surrounding air. A rocket engine produces thrust by reaction to exhaust expelled at high speed. Rocket engines work entir ...
s, or by spraying from aircraft.


Synthesis and reactions

Mustard gas can be synthesized in a variety of different ways. In the Depretz method, sulfur dichloride is treated with ethylene: : In the Levinstein process, disulfur dichloride is used instead: : + S8 In the Meyer method, thiodiglycol is produced from chloroethanol and potassium sulfide and chlorinated with
phosphorus trichloride Phosphorus trichloride is an inorganic compound with the chemical formula PCl3. A colorless liquid when pure, it is an important industrial chemical, being used for the manufacture of phosphites and other organophosphorus compounds. It is toxic ...
: : In the Meyer–Clarke method, concentrated
hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...
(HCl) is used instead of PCl3: : Thionyl chloride and phosgene, the latter of which is also a choking agent, have also been used as chlorinating agents. These compounds have the added advantage in that if they are used in excess, they remain as impurities in the finished product and can therefore produce additional mechanisms of toxicity. Mustard gas is a viscous liquid at normal temperatures. The pure compound has a melting point of and decomposes before boiling at . The idealized combustion of mustard gas in oxygen produces
hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...
and
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...
, in addition to carbon dioxide and water: : Phosgene, sulfur oxides, and chlorine are also produced in this process. Decontamination of mustard gas can be achieved with sodium hydroxide, giving divinyl sulfide: : Other compounds that have been used for decontamination include sodium ethoxide, which gives ethanol instead of water.


Mechanism of cellular toxicity

Sulfur mustards readily eliminate
chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...
ions by intramolecular nucleophilic substitution to form cyclic
sulfonium In organic chemistry, a sulfonium ion, also known as sulphonium ion or sulfanium ion, is a positively-charged ion (a "cation") featuring three organic substituents attached to sulfur. These organosulfur compounds have the formula . Together wi ...
ions. These very reactive intermediates tend to permanently alkylate
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...
s 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 would be another pathology involved in mustard gas toxicity. In the wider sense, compounds with the structural element BC2H4X, where X is any leaving group and B is a Lewis base, are known as ''mustards''. Such compounds can form cyclic "onium" ions (sulfonium, ammonium, etc.) that are good
alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
s. Other such compounds are bis(2-haloethyl)ethers (oxygen mustards), the (2-haloethyl)amines ( nitrogen mustards), and sesquimustard, which has two α-chloroethyl thioether groups (ClC2H4S−) connected by an ethylene bridge (−C2H4−). These compounds have a similar ability to alkylate DNA, but their physical properties vary.


Physiological effects

Mustard gases react with DNA, which interferes with cellular division and can lead to mutations. Mustard gases are extremely toxic and have powerful
blistering A blister is a small pocket of fluid in the upper layer of the skin caused by heat, electricity, chemicals, light, radiation, or friction Blister(s) or Blistering may also refer to: * Anti-torpedo bulge, also known as an anti-torpedo blister * '' ...
effects on victims. Their alkylating capabilities make them strongly
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
ic and mutagenic. Furthermore, they are highly lipophilic, which accelerates their absorption into the body. Because people exposed to mustard agents rarely suffer immediate symptoms, and contaminated areas may appear completely normal, victims can unknowingly receive high doses. Within 24 hours of exposure, victims experience intense itching and skin irritation. If this irritation goes untreated, blisters filled with yellow fluid ( pus) can start to form wherever the agent contacted the skin. These are chemical burns and are very debilitating. Mustard gases easily penetrate clothing fabrics such as wool or cotton, so it is not only exposed skin that gets burned. If the victim's eyes were exposed, then they become sore, starting with
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. Th ...
(also known as pink eye), 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 option. Miosis, when the pupil constricts more than usual, may also occur, which is probably the result of the cholinomimetic activity of mustard. At very high concentrations, if inhaled, mustard agents cause bleeding and blistering within the
respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies g ...
, damaging mucous membranes and causing
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due ...
. Depending on the level of contamination, mustard agent burns can vary between first and
second degree burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur main ...
s, though they can also be every bit as severe, disfiguring, and dangerous as
third degree burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur ...
s. Burns that are severe (i.e. covering more than 50% of the victim's skin) are often fatal, with death occurring after only days or weeks. Mild or moderate exposure to mustard gases is unlikely to kill, though victims still require lengthy periods of medical treatment and
convalescence Convalescence is the gradual recovery of health and strength after illness or injury. It refers to the later stage of an infectious disease or illness when the patient recovers and returns to previous health, but may continue to be a source of ...
before recovery is complete. Mustard gases' carcinogenic and mutagenic effects mean that victims, even if they fully recover, have an increased risk of developing
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
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. Mustard gases' blistering effects can be neutralized by
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
or chlorination, using household bleach ( sodium hypochlorite), or by nucleophilic attack using decontamination solutions such as "DS2" (2% NaOH, 70%
diethylenetriamine Diethylenetriamine (abbreviated and also known as 2,2’-Iminodi(ethylamine)) is an organic compound with the formula HN(CH2CH2NH2)2. This colourless hygroscopic liquid is soluble in water and polar organic solvents, but not simple hydrocarbon ...
, 28%
2-methoxyethanol 2-Methoxyethanol, or methyl cellosolve, is an organic compound with formula that is used mainly as a solvent. It is a clear, colorless liquid with an ether-like odor. It is in a class of solvents known as glycol ethers which are notable for ...
). After initial decontamination of the victim's wounds is complete, medical treatment is similar to that required by any conventional burn. The degree of pain and discomfort suffered by the victim is also comparable. Mustard agent burns do not heal quickly, and (as with other types of burns) present a risk of sepsis caused by
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s such as '' Staphylococcus aureus'' and ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...
''. 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 (NAC) 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 World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
commented:


Formulations

In its history, various types and mixtures of mustard gas have been employed. These include: * H – Also known as HS ("Hun Stuff") 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 Vapor pressure (or vapour pressure in English-speaking countries other than the US; see spelling differences) or equilibrium vapor pressure is defined as the pressure exerted by a vapor in thermodynamic equilibrium with its condensed pha ...
, 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% mustard and 40% O-mustard, a related vesicant with lower freezing point, lower volatility and similar vesicant characteristics. * HL – A blend of distilled mustard (HD) and lewisite (L), 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 (HD) and sesquimustard (Q) (Gates and Moore 1946).


Commonly-stockpiled mustard agents (class)


History


Development

Mustard gases were possibly developed as early as 1822 by
César-Mansuète Despretz César-Mansuète Despretz (4 May 1791, Lessines – 15 March 1863, Paris) was a chemist and physicist. He became a French citizen in 1838. A street got its name after him in Lessines (rue César Despretz). Biography In 1818, Despretz started ...
(1798–1863).By Any Other Name: Origins of Mustard Gas
. Itech.dickinson.edu (2008-04-25). Retrieved on 2011-05-29.
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 (1829–1908), 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 Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...
chemistry, repeated the reaction, and recorded blister-forming properties. In 1886,
Viktor Meyer Viktor Meyer (8 September 18488 August 1897) was a German chemist and significant contributor to both organic and inorganic chemistry. He is best known for inventing an apparatus for determining vapour densities, the Viktor Meyer apparatus, and ...
published a paper describing a synthesis that produced good yields. He combined
2-chloroethanol 2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like o ...
with aqueous potassium sulfide, and then treated the resulting thiodiglycol with
phosphorus trichloride Phosphorus trichloride is an inorganic compound with the chemical formula PCl3. A colorless liquid when pure, it is an important industrial chemical, being used for the manufacture of phosphites and other organophosphorus compounds. It is toxic ...
. 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 (psychosomatic symptoms), Meyer had this compound tested on laboratory rabbits, most of which died. In 1913, the English chemist
Hans Thacher Clarke Hans Thacher Clarke (27 December 1887 – 21 October 1972) was a prominent biochemist during the first half of the twentieth century. He was born in England where he received his university training, but also studied in Germany and Ireland. He sp ...
(known for the Eschweiler-Clarke reaction) replaced the phosphorus trichloride with
hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...
in Meyer's formulation while working with Emil Fischer in
Berlin Berlin ( , ) is the capital and largest city of Germany by both area and population. Its 3.7 million inhabitants make it the European Union's most populous city, according to population within city limits. One of Germany's sixteen constitu ...
. 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 The German Chemical Society (German: ', GDCh) is a learned society and professional association founded in 1949 to represent the interests of German chemists in local, national and international contexts. GDCh "brings together people working in ch ...
sent the
German Empire The German Empire (),Herbert Tuttle wrote in September 1881 that the term "Reich" does not literally connote an empire as has been commonly assumed by English-speaking people. The term literally denotes an empire – particularly a hereditary ...
on the road to chemical weapons. Mustard gas can have the effect of turning a patient's skin different colors, including shades of red, orange, pink, and in unusual cases, blue. The
German Empire The German Empire (),Herbert Tuttle wrote in September 1881 that the term "Reich" does not literally connote an empire as has been commonly assumed by English-speaking people. The term literally denotes an empire – particularly a hereditary ...
during
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
relied on the Meyer-Clarke method because
2-chloroethanol 2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like o ...
was readily available from the German dye industry of that time.


Use

Mustard gas was first used in World War I by the German army against British and Canadian soldiers near
Ypres Ypres ( , ; nl, Ieper ; vls, Yper; german: Ypern ) is a Belgian city and municipality in the province of West Flanders. Though the Dutch name is the official one, the city's French name is most commonly used in English. The municipality ...
, Belgium, "on the night of July 12, 1917." Later also against the French Second Army. ''Yperite'' is "a name used by the French, because the compound was first used at Ypres." The Allies did not use mustard gas until November 1917 at Cambrai, France, after the armies had captured a stockpile of German mustard shells. It took the British more than a year to develop their own mustard agent weapon, with production of the chemicals centred on Avonmouth Docks (the only option available to the British was the Despretz–Niemann–Guthrie process). This was used first in September 1918 during the breaking of the Hindenburg Line. Mustard gas was originally assigned the name LOST, after the scientists Wilhelm Lommel and Wilhelm Steinkopf, who developed a method of large-scale production for the Imperial German Army in 1916. Mustard gas was dispersed as an aerosol in a mixture with other chemicals, giving it a yellow-brown color. Mustard agent has also been dispersed in such munitions as aerial bombs, land mines, mortar rounds, artillery shells, and
rocket A rocket (from it, rocchetto, , bobbin/spool) is a vehicle that uses jet propulsion to accelerate without using the surrounding air. A rocket engine produces thrust by reaction to exhaust expelled at high speed. Rocket engines work entir ...
s. Exposure to mustard agent was lethal in about 1% of cases. Its effectiveness was as an
incapacitating agent The term incapacitating agent is defined by the United States Department of Defense as: :"An agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance of ...
. The early countermeasures against mustard agent were relatively ineffective, since a soldier wearing a gas mask was not protected against absorbing it through his skin and being blistered. A common countermeasure was using a urine-soaked mask or facecloth to prevent or reduce injury, a readily available remedy attested by soldiers in documentaries (e.g. ''They Shall Not Grow Old'' in 2018) and others (such as forward aid nurses) interviewed between 1947 and 1981 by the British Broadcasting Corporation for various World War One history programs; however, the effectiveness of this measure is unclear. Mustard gas can remain in the ground for weeks, and it continues to cause ill effects. If mustard agent contaminates one's clothing and equipment while cold, then other people with whom they share an enclosed space could become poisoned as contaminated items warm up enough material to become an airborne toxic agent. An example of this was depicted in a British and Canadian documentary about life in the trenches, particularly once the "sousterrain" (subways and berthing areas underground) were completed in Belgium and France. Towards the end of World War I, mustard agent was used in high concentrations as an area-denial weapon that forced troops to abandon heavily contaminated areas. Since World War I, mustard gas has been used in several wars and other conflicts, usually against people who cannot retaliate in kind:Blister Agent: Mustard gas (H, HD, HS)
, CBWinfo.com
* United Kingdom against the
Red Army The Workers' and Peasants' Red Army (Russian language, Russian: Рабо́че-крестья́нская Кра́сная армия),) often shortened to the Red Army, was the army and air force of the Russian Soviet Federative Socialist R ...
in 1919 * Alleged British use in Mesopotamia in 1920 *
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and
France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
against the Rifian resistance in
Morocco Morocco (),, ) officially the Kingdom of Morocco, is the westernmost country in the Maghreb region of North Africa. It overlooks the Mediterranean Sea to the north and the Atlantic Ocean to the west, and has land borders with Algeria to A ...
during the Rif War of 1921–27 (see also: '' Spanish use of chemical weapons in the Rif War'') *
Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical ...
in Libya in 1930 * The
Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nationa ...
in
Xinjiang Xinjiang, SASM/GNC: ''Xinjang''; zh, c=, p=Xīnjiāng; formerly romanized as Sinkiang (, ), officially the Xinjiang Uygur Autonomous Region (XUAR), is an autonomous region of the People's Republic of China (PRC), located in the northwes ...
, Republic of China, during the Soviet Invasion of Xinjiang against the
36th Division (National Revolutionary Army) The New 36th Division was a cavalry division in the National Revolutionary Army. It was created in 1932 by the Kuomintang for General Ma Zhongying, who was also its first commander. It was made almost entirely out of Hui Muslim troops, all of ...
in 1934, and also in the
Xinjiang War (1937) In 1937 an Islamic rebellion broke out in southern Xinjiang. The rebels were 1,500 Uighur Muslims led by Kichik Akhund, who was tacitly aided by the new 36th Division, against the pro-Soviet provincial forces of the puppet Sheng Shicai. St ...
in 1936–37 * Italy against
Abyssinia The Ethiopian Empire (), also formerly known by the exonym Abyssinia, or just simply known as Ethiopia (; Amharic and Tigrinya: ኢትዮጵያ , , Oromo: Itoophiyaa, Somali: Itoobiya, Afar: ''Itiyoophiyaa''), was an empire that historica ...
(now
Ethiopia Ethiopia, , om, Itiyoophiyaa, so, Itoobiya, ti, ኢትዮጵያ, Ítiyop'iya, aa, Itiyoppiya officially the Federal Democratic Republic of Ethiopia, is a landlocked country in the Horn of Africa. It shares borders with Eritrea to the ...
) in 1935-1936 * The Japanese Empire against
China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...
in 1937–1945 * The United States Government tested effectiveness on US Naval recruits in a laboratory setting at The Great Lakes Naval Base, June 3, 1945. * The 2 December 1943
air raid on Bari The air raid on Bari (german: Luftangriff auf den Hafen von Bari, it, Bombardamento di Bari) was an air attack by German bombers on Allied forces and shipping in Bari, Italy, on 2 December 1943, during World War II. 105 German Junkers Ju 88 b ...
destroyed an Allied stockpile of mustard gas on the SS ''John Harvey''. * Egypt against North Yemen in 1963–1967 * Iraq against
Kurds ug:كۇردلار Kurds ( ku, کورد ,Kurd, italic=yes, rtl=yes) or Kurdish people are an Iranian peoples, Iranian ethnic group native to the mountainous region of Kurdistan in Western Asia, which spans southeastern Turkey, northwestern Ir ...
in the town of Halabja during the Halabja chemical attack * Iraq against Iranians in 1983–1988 * Possibly in Sudan against insurgents in the
civil war A civil war or intrastate war is a war between organized groups within the same state (or country). The aim of one side may be to take control of the country or a region, to achieve independence for a region, or to change government polici ...
, in 1995 and 1997. * In the
Iraq War {{Infobox military conflict , conflict = Iraq War {{Nobold, {{lang, ar, حرب العراق (Arabic) {{Nobold, {{lang, ku, شەڕی عێراق (Kurdish languages, Kurdish) , partof = the Iraq conflict (2003–present), I ...
, abandoned stockpiles of mustard gas shells were destroyed in the open air, and were used against Coalition forces in roadside bombs. * By
ISIS Isis (; ''Ēse''; ; Meroitic: ''Wos'' 'a''or ''Wusa''; Phoenician: 𐤀𐤎, romanized: ʾs) was a major goddess in ancient Egyptian religion whose worship spread throughout the Greco-Roman world. Isis was first mentioned in the Old Kin ...
forces against Kurdish forces in Iraq in August 2015. * By ISIS against another rebel group in the town of Mare' in 2015. * According to Syrian State media, by ISIS against Syrian Army during the battle in Deir ez-Zor in 2016. In 1943, during World War II, a shipment of mustard gas from the US exploded aboard
SS John Harvey SS ''John Harvey'' was a U.S. World War II Liberty ship. This ship is best known for carrying a secret cargo of mustard gas and whose sinking by German aircraft in December 1943 at the port of Bari in south Italy caused an unintentional releas ...
that was bombed during an air raid in the harbor of Bari, Italy. Eighty-three of the 628 hospitalized victims who had been exposed to the mustard agent died. After WWII, stockpiled mustard gas was dumped by the British in the sea near Port Elizabeth, South Africa, resulting in many cases of burns among trawler crews. The use of toxic gases or other chemicals, including mustard gas, during warfare is known as chemical warfare, and this kind of warfare was prohibited by the Geneva Protocol of 1925, and also by the later Chemical Weapons Convention of 1993. The latter agreement also prohibits the development, production, stockpiling, and sale of such weapons. In September 2012, a US official stated that the rebel militant group
ISIS Isis (; ''Ēse''; ; Meroitic: ''Wos'' 'a''or ''Wusa''; Phoenician: 𐤀𐤎, romanized: ʾs) was a major goddess in ancient Egyptian religion whose worship spread throughout the Greco-Roman world. Isis was first mentioned in the Old Kin ...
was manufacturing and using mustard gas in Syria and Iraq, which was allegedly confirmed by the group's head of chemical weapons development, Sleiman Daoud al-Afari, who has since been captured.


Development of the first chemotherapy drug

As early as 1919 it was known that mustard agent was a suppressor of hematopoiesis. In addition, autopsies performed on 75 soldiers who had died of mustard agent during
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
were done by researchers from the
University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a Private university, private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest- ...
who reported decreased counts of white blood cells. This led the American Office of Scientific Research and Development (OSRD) to finance the biology and chemistry departments at
Yale University Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the w ...
to conduct research on the use of chemical warfare during World War II. As a part of this effort, the group investigated nitrogen mustard as a therapy for Hodgkin's lymphoma and other types of
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...
and
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
, and this compound was tried out on its first human patient in December 1942. The results of this study were not published until 1946, when they were declassified. In a parallel track, after the
air raid on Bari The air raid on Bari (german: Luftangriff auf den Hafen von Bari, it, Bombardamento di Bari) was an air attack by German bombers on Allied forces and shipping in Bari, Italy, on 2 December 1943, during World War II. 105 German Junkers Ju 88 b ...
in December 1943, the doctors of the U.S. Army noted that white blood cell counts were reduced in their patients. Some years after World War II was over, the incident in Bari and the work of the Yale University group with nitrogen mustard converged, and this prompted a search for other similar
chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s. Due to its use in previous studies, the nitrogen mustard called "HN2" became the first cancer
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
drug,
mustine Chlormethine (INN, BAN), also known as mechlorethamine (USAN, USP), mustine, HN2, and (in post-Soviet states) embikhin (эмбихин), is a nitrogen mustard sold under the brand name Mustargen among others. It is the prototype of alkylating ...
(also called chlormethine), to be used.


Disposal

In the United States, storage and incineration of mustard gas and other chemical weapons were carried out by the U.S. Army Chemical Materials Agency. Disposal projects at the two remaining American chemical weapons sites were carried out near Richmond, Kentucky, and
Pueblo, Colorado Pueblo () is a home rule municipality that is the county seat and the most populous municipality of Pueblo County, Colorado, United States. The city population was 111,876 at the 2020 United States Census, making Pueblo the ninth most popu ...
. Although not yet declassified, toxicology specialists who dealt with the accidental puncturing of World War I gas stockpiles add that Air Force bases in Colorado have been made available to assist veterans of the 2003 American war with Iraq in which many Marines were exposed to gas as caches of up to . The United Nations definition of a weapon of mass destruction for mustard gas is , typically the Marines and other coalition allies discovered caches of located across a road from caches as multiple memoirs attest. These were discovered by the assistance of host country allies, or through leaks affecting personnel in an area with a weapon and gas cache called an ASP. New detection techniques are being developed in order to detect the presence of mustard gas and its metabolites. The technology is portable and detects small quantities of the hazardous waste and its oxidized products, which are notorious for harming unsuspecting civilians. The immunochromatographic assay would eliminate the need for expensive, time-consuming lab tests and enable easy-to-read tests to protect civilians from sulfur-mustard dumping sites. In 1946, 10,000 drums of mustard gas (2,800 tonnes) stored at the production facility of Stormont Chemicals in Cornwall, Ontario, Canada, were loaded onto 187 boxcars for the journey to be buried at sea on board a long barge south of Sable Island, southeast of Halifax, at a depth of . The dump location is 42 degrees, 50 minutes north by 60 degrees, 12 minutes west. A large British stockpile of old mustard agent that had been made and stored since World War I at
M. S. Factory, Valley The M.S. (Ministry of Supply) Factory, Valley was a Second World War site in Rhydymwyn, Flintshire, Wales, that was used for the storage and production of mustard gas. It was later also used in the development of the UK's atomic bomb project. Mor ...
near Rhydymwyn in Flintshire, Wales, was destroyed in 1958. Most of the mustard gas found in Germany after
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
was dumped into the
Baltic Sea The Baltic Sea is an arm of the Atlantic Ocean that is enclosed by Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Poland, Russia, Sweden and the North and Central European Plain. The sea stretches from 53°N to 66°N latitude and from ...
. Between 1966 and 2002, fishermen have found about 700 chemical weapons in the region of Bornholm, most of which contain mustard gas. One of the more frequently dumped weapons was "Sprühbüchse 37" (SprüBü37, Spray Can 37, 1937 being the year of its fielding with the German Army). These weapons contain mustard gas mixed with a thickener, which gives it a tar-like viscosity. When the content of the SprüBü37 comes in contact with water, only the mustard gas in the outer layers of the lumps of viscous mustard
hydrolyzes Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...
, leaving behind amber-colored residues that still contain most of the active mustard gas. On mechanically breaking these lumps (e.g., with the drag board of a fishing net or by the human hand) the enclosed mustard gas is still as active as it had been at the time the weapon was dumped. These lumps, when washed ashore, can be mistaken for amber, which can lead to severe health problems. Artillery shells containing mustard gas and other toxic ammunition from World War I (as well as conventional explosives) can still be found in France and Belgium. These were formerly disposed of by explosion undersea, but since the current environmental regulations prohibit this, the
French government The Government of France ( French: ''Gouvernement français''), officially the Government of the French Republic (''Gouvernement de la République française'' ), exercises executive power in France. It is composed of the Prime Minister, who ...
is building an automated factory to dispose of the accumulation of chemical shells. In 1972, the U.S. Congress banned the practice of disposing of chemical weapons into the ocean by the United States. 29,000 tons of nerve and mustard agents had already been dumped into the ocean off the United States by the U.S. Army. According to a report created in 1998 by William Brankowitz, a deputy project manager in the
U.S. Army Chemical Materials Agency The United States Army Chemical Materials Activity (CMA) is a separate reporting activity of the United States Army Materiel Command (AMC). Its role is to enhance national security by securely storing the remaining U.S. chemical warfare materiel ...
, the army created at least 26 chemical weapons dumping sites in the ocean offshore from at least 11 states on both the East Coast and the West Coast (in
Operation CHASE Operation CHASE (an acronym for "Cut Holes And Sink 'Em") was a United States Department of Defense program for the disposal of unwanted munitions at sea from May 1964 until the early 1970s.Kurak, Steve "Operation Chase" ''United States Naval Instit ...
, Operation Geranium, etc.). In addition, due to poor recordkeeping, about one-half of the sites have only their rough locations known. In June 1997, India declared its stock of chemical weapons of of mustard gas. By the end of 2006, India had destroyed more than 75 percent of its chemical weapons/material stockpile and was granted extension for destroying the remaining stocks by April 2009 and was expected to achieve 100 percent destruction within that time frame. India informed the United Nations in May 2009 that it had destroyed its stockpile of chemical weapons in compliance with the international Chemical Weapons Convention. With this India has become the third country after South Korea and Albania to do so. This was cross-checked by inspectors of the United Nations. Producing or stockpiling mustard gas is prohibited by the Chemical Weapons Convention. When the convention entered force in 1997, the parties declared worldwide stockpiles of 17,440 tonnes of mustard gas. As of December 2015, 86% of these stockpiles had been destroyed. A significant portion of the United States' mustard agent
stockpile A stockpile is a pile or storage location for bulk materials, forming part of the bulk material handling process. Stockpiles are used in many different areas, such as in a port, refinery or manufacturing facility. The stockpile is normally cre ...
was stored at the Edgewood Area of Aberdeen Proving Ground in
Maryland Maryland ( ) is a state in the Mid-Atlantic region of the United States. It shares borders with Virginia, West Virginia, and the District of Columbia to its south and west; Pennsylvania to its north; and Delaware and the Atlantic Ocean t ...
. Approximately 1,621 tons of mustard agents were stored in one-ton containers on the base under heavy guard. A chemical neutralization plant was built on the proving ground and neutralized the last of this stockpile in February 2005. This stockpile had priority because of the potential for quick reduction of risk to the community. The nearest schools were fitted with overpressurization machinery to protect the students and faculty in the event of a catastrophic explosion and fire at the site. These projects, as well as planning, equipment, and training assistance, were provided to the surrounding community as a part of the Chemical Stockpile Emergency Preparedness Program (CSEPP), a joint program of the Army and the Federal Emergency Management Agency (FEMA). Unexploded shells containing mustard gases and other chemical agents are still present in several test ranges in proximity to schools in the Edgewood area, but the smaller amounts of poison gas () present considerably lower risks. These remnants are being detected and excavated systematically for disposal. The U.S. Army Chemical Materials Agency oversaw disposal of several other chemical weapons stockpiles located across the United States in compliance with international chemical weapons treaties. These include the complete incineration of the chemical weapons stockpiled in
Alabama (We dare defend our rights) , anthem = " Alabama" , image_map = Alabama in United States.svg , seat = Montgomery , LargestCity = Huntsville , LargestCounty = Baldwin County , LargestMetro = Greater Birmingham , area_total_km2 = 135,7 ...
,
Arkansas Arkansas ( ) is a landlocked state in the South Central United States. It is bordered by Missouri to the north, Tennessee and Mississippi to the east, Louisiana to the south, and Texas and Oklahoma to the west. Its name is from the O ...
,
Indiana Indiana () is a U.S. state in the Midwestern United States. It is the 38th-largest by area and the 17th-most populous of the 50 States. Its capital and largest city is Indianapolis. Indiana was admitted to the United States as the 19th ...
, and
Oregon Oregon () is a U.S. state, state in the Pacific Northwest region of the Western United States. The Columbia River delineates much of Oregon's northern boundary with Washington (state), Washington, while the Snake River delineates much of it ...
. Earlier, this agency had also completed destruction of the chemical weapons stockpile located on Johnston Atoll located south of
Hawaii Hawaii ( ; haw, Hawaii or ) is a state in the Western United States, located in the Pacific Ocean about from the U.S. mainland. It is the only U.S. state outside North America, the only state that is an archipelago, and the only stat ...
in the
Pacific Ocean The Pacific Ocean is the largest and deepest of Earth's five oceanic divisions. It extends from the Arctic Ocean in the north to the Southern Ocean (or, depending on definition, to Antarctica) in the south, and is bounded by the conti ...
. The largest mustard agent stockpile, at approximately 6,200 short tons, was stored at the
Deseret Chemical Depot The Deseret Chemical Depot () was a U.S. Army chemical weapon storage area located in Utah, 60 miles (100 km) southwest of Salt Lake City. It is related to the Tooele Chemical Agent Disposal Facility. History The area was used to store chemi ...
in northern
Utah Utah ( , ) is a state in the Mountain West subregion of the Western United States. Utah is a landlocked U.S. state bordered to its east by Colorado, to its northeast by Wyoming, to its north by Idaho, to its south by Arizona, and to its ...
. The incineration of this stockpile began in 2006. In May 2011, the last of the mustard agents in the stockpile were incinerated at the Deseret Chemical Depot, and the last artillery shells containing mustard gas were incinerated in January 2012. In 2008, many empty aerial bombs that contained mustard gas were found in an excavation at the Marrangaroo Army Base just west of Sydney, Australia.Chemical Warfare in Australia
Mustardgas.org. Retrieved on 29 May 2011.
In 2009, a mining survey near
Chinchilla, Queensland Chinchilla is a rural town and locality in the Western Downs Region, Queensland, Australia. In the , the locality of Chinchilla had a population of 6,612 people. Chinchilla is known as the 'Melon Capital of Australia', and plays host to a Melo ...
, uncovered 144 105-millimeter howitzer shells, some containing "Mustard H", that had been buried by the U.S. Army during World War II. In 2014, a collection of 200 bombs was found near the Flemish villages of Passendale and Moorslede. The majority of the bombs were filled with mustard agents. The bombs were left over from the German army and were meant to be used in the
Battle of Passchendale The Third Battle of Ypres (german: link=no, Dritte Flandernschlacht; french: link=no, Troisième Bataille des Flandres; nl, Derde Slag om Ieper), also known as the Battle of Passchendaele (), was a campaign of the First World War, fought by t ...
in World War I. It was the largest collection of chemical weapons ever found in Belgium. A large amount of chemical weapons, including mustard gas, was found in a neighborhood of Washington DC. The cleanup was completed in 2021.


Post-war accidental exposure

In 2002, an archaeologist at the Presidio Trust archaeology lab in San Francisco was exposed to mustard gas, which had been dug up at the Presidio of San Francisco, a former military base. In 2010, a clamming boat pulled up some old
artillery Artillery is a class of heavy military ranged weapons that launch munitions far beyond the range and power of infantry firearms. Early artillery development focused on the ability to breach defensive walls and fortifications during si ...
shells of World War I from the
Atlantic Ocean The Atlantic Ocean is the second-largest of the world's five oceans, with an area of about . It covers approximately 20% of Earth's surface and about 29% of its water surface area. It is known to separate the " Old World" of Africa, Europe ...
south of Long Island, New York. Multiple fishermen suffered from blistering and respiratory irritation severe enough to require hospitalization.


WWII-era tests on men

From 1943 to 1944, mustard agent experiments were performed on Australian service volunteers in tropical Queensland, Australia, by
British Army The British Army is the principal land warfare force of the United Kingdom, a part of the British Armed Forces along with the Royal Navy and the Royal Air Force. , the British Army comprises 79,380 regular full-time personnel, 4,090 Gurkha ...
and American experimenters, resulting in some severe injuries. One test site, the
Brook Islands National Park The Brook Islands National Park is a national park in Cassowary Coast Region, Queensland, Australia, 1246 km northwest of Brisbane, with an area of 0.9 km2. It was established in 1994 and comprises three islands (North, Tween and Mi ...
, was chosen to simulate Pacific islands held by the
Imperial Japanese Army The was the official ground-based armed force of the Empire of Japan from 1868 to 1945. It was controlled by the Imperial Japanese Army General Staff Office and the Ministry of the Army, both of which were nominally subordinate to the Emper ...
. The United States tested sulfur mustards and other chemical agents including nitrogen mustards and lewisite on up to 60,000 servicemen during and after WWII. The experiments were classified secret and as with Agent Orange, claims for medical care and compensation were routinely denied, even after the WWII-era tests were declassified in 1993. The Department of Veterans Affairs stated that it would contact 4,000 surviving test subjects but failed to do so, eventually only contacting 600. Skin cancer, severe eczema, leukemia, and chronic breathing problems plagued the test subjects, some of whom were as young as 19 at the time of the tests, until their deaths, but even those who had previously filed claims with the VA went without compensation. African-American servicemen were tested alongside white men in separate trials to determine whether their skin color would afford them a degree of immunity to the agents, and Nisei servicemen, some of whom had joined after their release from Japanese American Internment Camps were tested to determine susceptibility of Japanese military personnel to these agents. These tests also included Puerto-Rican subjects.


Detection in biological fluids

Concentrations of thiodiglycol in urine have been used to confirm a diagnosis of chemical poisoning in hospitalized victims. The presence in urine of 1,1'-sulfonylbismethylthioethane (SBMTE), a conjugation product with glutathione, is considered a more specific marker, since this metabolite is not found in specimens from unexposed persons. In one case, intact mustard gas was detected in postmortem fluids and tissues of a man who died one week post-exposure.R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 10th edition, Biomedical Publications, Seal Beach, CA, 2014, pp. 1892–1894.


See also

*
Bis(chloromethyl) ether Bis(chloromethyl) ether is an organic compound with the chemical formula (CH2Cl)2O. It is a colourless liquid with an unpleasant suffocating odour and it is one of the chloroalkyl ethers. Bis(chloromethyl) ether was once produced on a large scale ...
*
Blister agent A blister agent (or vesicant), is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affec ...
* Chlorine gas * Half mustard * Keen as Mustard * Lewisite * Nitrogen mustard *
Phosgene oxime Phosgene oxime, or CX, is an organic compound with the formula Cl2CNOH. It is a potent chemical weapon, specifically a nettle agent. The compound itself is a colorless solid, but impure samples are often yellowish liquids. It has a strong, dis ...
* Poison gas in World War I * Rawalpindi experiments * Selenium mustard *
Yellow Cross (chemical warfare) Yellow Cross (Gelbkreuz) is a World War I chemical warfare agent usually based on sulfur mustard (mustard gas, HS, Yperite, Lost). The original Gelbkreuz was a composition of 80–90% of sulfur mustard and 10–20% of tetrachloromethane or chlo ...
* Mustard (condiment)


Further reading


Mustard gas (Sulphur Mustard) (IARC Summary & Evaluation, Supplement7, 1987)
Inchem.org (1998-02-09). Retrieved on 2011-05-29. * * *
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.


References


External links


Textbook of Military Medicine – Intensive overview of mustard gas
Includes many references to scientific literature

* Shows photographs taken in 1996 showing people with mustard gas burns.

(Caution: contains graphic images)


UMDNJ-Rutgers University CounterACT Research Center of Excellence
A research center studying mustard gas, include
searchable reference library
with many early references on mustard gas. *


surgical treatment of mustard gas burns

UK Ministry of Defence Report on disposal of weapons at sea and incidents arising

Rhydymwyn Valley History Society

The advent of mustard gas in 1917, Simon Jones

Measures to protect against mustard gas, 1917-1918, Simon Jones
{{DEFAULTSORT:Mustard gas Thioethers Organochlorides Blister agents World War I chemical weapons IARC Group 1 carcinogens Chloroethyl compounds Sulfur mustards