Editing Mustard gas (section)

==Adverse health effects==
[[File:Mustard gas burns.jpg|thumb|Soldier with moderate mustard agent burns sustained during [[World War I]] showing characteristic [[Bulla (dermatology)|bullae]] on the neck, armpit, and hands]]

Mustard gases have powerful [[vesicant|blistering]] effects on victims. They are also [[carcinogen]]ic and [[mutagen]]ic [[alkylating agents]].<ref name=pubchem/> Their high [[lipophilic]]ity accelerates their absorption into the body.<ref name="opcw.org" /> Because mustard agents often do not elicit immediate symptoms, contaminated areas may appear normal.<ref name=who/> Within 24 hours of exposure, victims experience intense [[itch]]ing and skin irritation. If this irritation goes untreated, blisters filled with [[pus]] can form wherever the agent contacted the skin.<ref name=who/> As [[chemical burn]]s, these are severely debilitating.<ref name=pubchem/> Mustard gas can have the effect of turning a patient's skin different colors due to melanogenesis.<ref name=":0" /><ref name=who/> 

If the victim's eyes were exposed, then they become sore, starting with [[conjunctivitis]] (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 ulcer]]ation, anterior chamber scarring, and [[neovascularization]].<ref>{{Cite journal|last1=Ghasemi|first1=Hassan|last2=Javadi|first2=Mohammad Ali|last3=Ardestani|first3=Sussan K.|last4=Mahmoudi|first4=Mahmoud|last5=Pourfarzam|first5=Shahryar|last6=Mahdavi|first6=Mohammad Reza Vaez|last7=Yarmohammadi|first7=Mohammad Ebrahim|last8=Baradaran-Rafii|first8=Alireza|last9=Jadidi|first9=Khosro|last10=Shariatpanahi|first10=Shamsa|last11=Rastin|first11=Maryam|date=2020|title=Alteration in inflammatory mediators in seriously eye-injured war veterans, long-term after sulfur mustard exposure|url=https://pubmed.ncbi.nlm.nih.gov/31685435|journal=International Immunopharmacology|volume=80|pages=105897|doi=10.1016/j.intimp.2019.105897|issn=1878-1705|pmid=31685435|s2cid=207899509}}</ref><ref>{{Cite journal|last1=Ghazanfari|first1=Tooba|last2=Ghasemi|first2=Hassan|last3=Yaraee|first3=Roya|last4=Mahmoudi|first4=Mahmoud|last5=Javadi|first5=Mohammad Ali|last6=Soroush|first6=Mohammad Reza|last7=Faghihzadeh|first7=Soghrat|last8=Majd|first8=Ali Mohammad Mohseni|last9=Shakeri|first9=Raheleh|last10=Babaei|first10=Mahmoud|last11=Heidary|first11=Fatemeh|date=2019|title=Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients|url=https://pubmed.ncbi.nlm.nih.gov/31669888|journal=International Immunopharmacology|volume=77|pages=105844|doi=10.1016/j.intimp.2019.105844|issn=1878-1705|pmid=31669888|s2cid=204967476}}</ref><ref>{{Cite journal|last1=Heidary|first1=Fatemeh|last2=Gharebaghi|first2=Reza|last3=Ghasemi|first3=Hassan|last4=Mahdavi|first4=Mohammad Reza Vaez|last5=Ghaffarpour|first5=Sara|last6=Naghizadeh|first6=Mohammad Mehdi|last7=Ghazanfari|first7=Tooba|date=2019|title=Angiogenesis modulatory factors in subjects with chronic ocular complications of Sulfur Mustard exposure: A case-control study|url=https://pubmed.ncbi.nlm.nih.gov/31629219|journal=International Immunopharmacology|volume=76|pages=105843|doi=10.1016/j.intimp.2019.105843|issn=1878-1705|pmid=31629219|s2cid=204799405}}</ref><ref>{{Cite journal|last1=Heidary|first1=Fatemeh|last2=Ardestani|first2=Sussan K.|last3=Ghasemi|first3=Hassan|last4=Javadi|first4=Mohammad Ali|last5=Mahmoudi|first5=Mahmoud|last6=Yaraee|first6=Roya|last7=Shams|first7=Jalaledin|last8=Falahi|first8=Faramarz|last9=Sedighi Moghadam|first9=Mohamad Reza|last10=Shariatpanahi|first10=Shamsa|last11=Shakeri|first11=Raheleh|date=2019|title=Alteration in serum levels of ICAM-1 and P-, E- and L-selectins in seriously eye-injured long-term following sulfur-mustard exposure|url=https://pubmed.ncbi.nlm.nih.gov/31480003|journal=International Immunopharmacology|volume=76|pages=105820|doi=10.1016/j.intimp.2019.105820|issn=1878-1705|pmid=31480003|s2cid=201831881}}</ref> In these severe and infrequent cases, [[corneal transplantation]] has been used as a treatment.<ref>{{cite journal |title=Ocular injuries caused by mustard gas: diagnosis, treatment, and medical defense|journal= Military Medicine|volume=166|issue=1|pages=67–70|pmid=11197102|year=2001|last1=Safarinejad|first1=M. R.|last2=Moosavi|first2=S. A.|last3=Montazeri|first3=B|doi=10.1093/milmed/166.1.67|doi-access=free}}</ref> [[Miosis]], when the pupil constricts more than usual, may also occur, which may be the result of the cholinomimetic activity of mustard.<ref>[http://www.brooksidepress.org/Products/OperationalMedicine/DATA/operationalmed/Manuals/RedHandbook/004Vesicants.htm Vesicants]. brooksidepress.org</ref> If inhaled in high concentrations, mustard agents cause bleeding and blistering within the [[respiratory system]], damaging [[mucous membrane]]s and causing [[pulmonary edema]].<ref name=who/> Depending on the level of contamination, mustard agent burns can vary between [[first degree burn|first]] and [[second degree burn]]s. They can also be as severe, disfiguring, and dangerous as [[third degree burn]]s. 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.<ref name=pubchem/>

The carcinogenic and mutagenic effects of exposure to mustard gas increase the risk of developing [[cancer]] later in life.<ref name=pubchem/> 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.<ref>{{cite journal |doi=10.3109/10799893.2014.896379 |pmid=24823320 |url= https://www.researchgate.net/publication/262303374 |title=Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard|journal= Journal of Receptors and Signal Transduction|volume=34|issue=4|pages=283–9|year=2014|last1=Najafi|first1=Ali|last2=Masoudi-Nejad|first2=Ali|last3=Imani Fooladi|first3=Abbas Ali|last4=Ghanei|first4=Mostafa|last5=Nourani|first5=Mohamad Reza|s2cid=41665583 }}</ref> The long-term ocular complications include burning, tearing, itching, [[photophobia]], [[presbyopia]], pain, and foreign-body sensations.<ref name=who/><ref>{{Cite journal|last1=Ghasemi|first1=Hassan|last2=Javadi|first2=Mohammad Ali|last3=Ardestani|first3=Sussan K.|last4=Mahmoudi|first4=Mahmoud|last5=Pourfarzam|first5=Shahryar|last6=Mahdavi|first6=Mohammad Reza Vaez|last7=Yarmohammadi|first7=Mohammad Ebrahim|last8=Baradaran-Rafii|first8=Alireza|last9=Jadidi|first9=Khosro|last10=Shariatpanahi|first10=Shamsa|last11=Rastin|first11=Maryam|date=2020|title=Alteration in inflammatory mediators in seriously eye-injured war veterans, long-term after sulfur mustard exposure|url=https://linkinghub.elsevier.com/retrieve/pii/S1567576919311853|journal=International Immunopharmacology|language=en|volume=80|pages=105897|doi=10.1016/j.intimp.2019.105897|pmid=31685435|s2cid=207899509}}</ref><ref>{{Cite journal|last=Geraci|first=Matthew J.|date=2008|title=Mustard gas: imminent danger or eminent threat?|journal=The Annals of Pharmacotherapy|volume=42|issue=2|pages=237–246|doi=10.1345/aph.1K445|issn=1542-6270|pmid=18212254|s2cid=207263000}}</ref>
[[File:blister-arm.jpg|right|thumb|Typical appearance of [[Bulla (dermatology)|bullae]] on an arm caused by vesicant burns]]

===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.<ref name=who/> The eyes should be thoroughly rinsed using saline or clean water. A topical analgesic is used to relieve skin pain during decontamination.<ref name=who/> For skin lesions, topical treatments, such as [[calamine|calamine lotion]], steroids, and oral [[antihistamine]]s are used to relieve itching.<ref name="who" /> Larger blisters are irrigated repeatedly with saline or soapy water, then treated with an antibiotic and petroleum gauze.<ref name="who" />

Mustard agent burns do not heal quickly and (as with other types of burns) present a risk of [[sepsis]] caused by [[pathogen]]s 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 [[Acetylcysteine|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.<ref>{{cite journal |doi=10.1006/taap.1996.0324 |pmid=8975783 |title=Sulfur Mustard Induces Apoptosis and Necrosis in Endothelial Cells |journal= Toxicology and Applied Pharmacology|volume=141 |issue=2 |pages=568–83 |year=1996 |last1=Dabrowska |first1=Milena I. |last2=Becks |first2=Lauren L. |last3=Lelli |first3=Joseph L. Jr. |last4=Levee |first4=Minette G. |last5=Hinshaw |first5=Daniel B. |bibcode=1996ToxAP.141..568D }}</ref>

A British nurse treating soldiers with mustard agent burns during [[World War I]] commented:<ref>{{cite book|author=Van Bergen, Leo |title=Before My Helpless Sight: Suffering, Dying and Military Medicine on the Western Front, 1914–1918|url=https://books.google.com/books?id=qR-mzZkvaMoC&pg=PA184|year=2009|publisher=Ashgate Publishing, Ltd.|isbn=978-0-7546-5853-5|page=184}}</ref>

{{Blockquote|They cannot be bandaged or touched. We cover them with a tent of propped-up sheets. Gas burns must be agonizing because usually the other cases do not complain, even with the worst wounds, but gas cases are invariably beyond endurance and they cannot help crying out.}}

===Mechanism of cellular toxicity===
[[File:Mustard-dna.svg|thumb|upright=1.8|Mustard gas alkylating an amino group via conversion to a sulfonium ion (2-chloroethylthiiranium)]]
Sulfur mustards readily eliminate [[chloride]] ions by intramolecular [[nucleophilic substitution]] to form cyclic [[sulfonium]] ions. These very reactive intermediates tend to permanently [[alkylation|alkylate]] [[nucleotide]]s in [[DNA]] strands, which can prevent cellular division, leading to [[apoptosis|programmed cell death]].<ref name="opcw.org">[http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/mustard-agents/ Mustard agents: description, physical and chemical properties, mechanism of action, symptoms, antidotes and methods of treatment]. Organisation for the Prohibition of Chemical Weapons. Accessed June 8, 2010.</ref> Alternatively, if cell death is not immediate, the damaged DNA can lead to the development of cancer.<ref name="opcw.org" /> [[Oxidative stress]] is another pathology involved in mustard gas toxicity.<ref>{{Cite journal |last=Ghabili |first=Kamyar |last2=Agutter |first2=Paul S. |last3=Ghanei |first3=Mostafa |last4=Ansarin |first4=Khalil |last5=Shoja |first5=Mohammadali M. |date=October 2010 |title=Mustard gas toxicity: the acute and chronic pathological effects |url=https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jat.1581 |journal=Journal of Applied Toxicology |language=en |volume=30 |issue=7 |pages=627–643 |doi=10.1002/jat.1581 |issn=0260-437X}}</ref>

Various compounds with the structural subgroup BC<sub>2</sub>H<sub>4</sub>X, where X is any [[leaving group]] and B is a [[Lewis base]], have a common name of mustard. Such compounds can form cyclic [[onium ion|"onium" ions]] (sulfonium, [[ammonium]], etc.) that are good [[alkylating agent]]s. These compoudsn include bis(2-haloethyl)ethers ([[Bis(chloroethyl) ether|oxygen mustards]]), the (2-haloethyl)amines ([[nitrogen mustard]]s), and [[sesquimustard]], which has two α-chloroethyl thioether groups (ClC<sub>2</sub>H<sub>4</sub>S−) connected by an ethylene bridge (−C<sub>2</sub>H<sub>4</sub>−). These compounds have a similar ability to alkylate DNA, but their physical properties vary.