Editing Methyl isocyanate (section)

== Toxicity ==
Methyl isocyanate is extremely [[toxic]]. There is no known [[antidote]]. The threshold limit value set by the American Conference of Governmental Industrial Hygienists is 0.02 [[Parts per million|ppm]]. MIC is toxic by inhalation, ingestion and contact in quantities as low as 0.4 [[Parts per million|ppm]]. Exposure symptoms include coughing, [[chest]] pain, [[dyspnea]], [[asthma]], irritation of the [[Human eye|eye]]s, [[human nose|nose]] and [[throat]], as well as [[skin]] damage. Higher levels of exposure, over 21 ppm, can result in pulmonary or lung [[edema]], [[emphysema]] and [[hemorrhage]]s, bronchial [[pneumonia]] and [[death]]. Although the odor of methyl isocyanate cannot be detected at 5 ppm by most people, its potent [[Lachrymatory agent|lachrymal]] properties provide an excellent warning of its presence (at a concentration of 2–4 parts per million (ppm) subjected to eyes are irritated, while at 21 ppm, subjects could not tolerate the presence of methyl isocyanate in air).<ref name=Kimmerle>{{cite journal |vauthors=Kimmerle G, Eben A |title=Zur Toxizität von Methylisocyanat und dessen quantitativer Bestimmung in der Luft |journal=Archiv für Toxikologie |year=1964 |volume=20 |issue=4 |pages=235–241 |s2cid=21422558 |doi=10.1007/bf00577897|bibcode=1964ArTox..20..235K }}</ref> The irritant effects of methyl isocyanate are mediated by the irritant and tear gas receptor [[TRPA1]] in pain-sensing nerve endings in the eye.<ref>{{Cite journal |last1=Bessac |first1=Bret F. |last2=Sivula |first2=Michael |last3=Hehn |first3=Christian A. |last4=Caceres |first4=Ana I. |last5=Escalera |first5=Jasmine |last6=Jordt |first6=Sven-Eric |date=2009-04-01 |title=Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases |journal=The FASEB Journal |language=en |volume=23 |issue=4 |pages=1102–1114 |doi=10.1096/fj.08-117812 |doi-access=free |issn=0892-6638 |pmc=2660642 |pmid=19036859}}</ref> 

Proper care must be taken to store methyl isocyanate because of its ease of exothermically polymerizing (see [[#Reactions|Reactions]]) and its similar sensitivity to water. Only [[stainless steel]] or [[glass]] containers may be safely used; the MIC must be stored at temperatures below {{convert|40|°C}} and preferably at {{convert|4|°C}}.{{Citation needed|date=August 2018}}

The toxic effect of the compound was apparent in the 1984 [[Bhopal disaster]], when around {{convert|42000|kg}} of methyl isocyanate and other gases were released from the underground reservoirs of the [[Union Carbide India Limited]] (UCIL) factory, over a populated area on 3 December 1984, killing about 3,500 people immediately, 8,000 people in the first 48 hours and 15,000 more over the next several years. 200,000 people had lasting health effects from the disaster.<ref>{{cite journal |last1=Varma |first1=Daya |last2=Mulay |first2=Shree |title=Methyl Isocyanate: The Bhopal Gas |journal=Handbook of Toxicology of Chemical Warfare Agents |date=2015 |pages=287–299 |doi=10.1016/B978-0-12-800159-2.00022-1}}</ref><ref name="convictions">{{cite news |url=http://news.bbc.co.uk/1/hi/world/south_asia/8725140.stm |title=Bhopal trial: Eight convicted over India gas disaster |date=7 June 2010 |publisher=[[BBC News]] |access-date=7 June 2010 | archive-url=https://web.archive.org/web/20100607185745/http://news.bbc.co.uk/1/hi/world/south_asia/8725140.stm |archive-date=7 June 2010 |url-status=live}}</ref>

During structural fires, natural materials can contribute to releasing isocyanates including methyl isocyanate.<ref>Dzhordzhio Naldzhiev, Matija Strlic; Polyurethane insulation and household products – a systematic review of their impact on indoor environmental quality, [Building and Environment https://www.sciencedirect.com/journal/building-and-environment], 2020</ref>

=== Mechanism of action ===
Until recent decades, the mechanism of methyl isocyanate toxicity in humans was largely unknown or unclear.<ref>{{cite journal |vauthors=Mehta PS, Mehta AS, Mehta SJ, Makhijani AB |title=Bhopal tragedy's health effects. A review of methyl isocyanate toxicity |journal=JAMA |volume=264 |issue=21 |pages=2781–2787 |date=December 1990 |pmid=2232065 |doi=10.1001/jama.1990.03450210081037}}</ref><ref>{{cite journal |vauthors=Varma DR |title=Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy |journal=Environmental Health Perspectives |volume=72 |pages=153–157 |date=June 1987 |pmid=3622430 |pmc=1474644 |doi=10.1289/ehp.8772153}}</ref> Methyl isocyanate and other [[isocyanate]]s are [[electrophile]]s and are currently thought to cause toxicity by the [[alkylation]] of biomolecules.<ref>{{cite journal |last1=Bessac |first1=B.F. |last2=Jordt |first2=S.-E. |date=2010-07-01 |title=Sensory Detection and Responses to Toxic Gases: Mechanisms, Health Effects, and Countermeasures |journal=Proceedings of the American Thoracic Society |volume=7 |issue=4 |pages=269–277 |pmid=20601631 |pmc=3136963 |issn=1546-3222 |doi=10.1513/pats.201001-004sm}}</ref> The mechanism of methyl isocyanate was previously suspected to be the [[carbamylation]] of [[hemoglobin]], thus interfering with its oxygen-binding capability and causing [[Hypoxia (medical)|hypoxia]]. However, experiments showed that when [[rat]]s and [[guinea pig]]s were exposed to methyl isocyanate at [[concentration]]s above the [[Median lethal dose|median lethal concentration]] ([[Median lethal dose|LC<sub>50</sub>]], the concentration sufficient to kill 50% of the tested population), only 2% of hemoglobin molecules were carbamylated, suggesting that this is probably not the mechanism of toxicity.<ref>{{cite journal |last1=Varma |first1=Daya R.|last2=Guest |first2=Ian |date=1993 |title=The Bhopal accident and methyl isocyanate toxicity |journal=Journal of Toxicology and Environmental Health |volume=40 |issue=4 |pages=513–529 |pmid=8277516 |bibcode=1993JTEH...40..513V |issn=0098-4108 |doi=10.1080/15287399309531816}}</ref><ref>{{cite journal |last1=Ramachandran |first1=P.K. |last2=Gandhe |first2=B.R. |last3=Venkateswaran |first3=K.S. |last4=Kaushik |first4=M.P. |last5=Vijayaraghavan |first5=R. |last6=Agarwal |first6=G.S. |last7=Gopalan |first7=N. |last8=Suryanarayana |first8=M.V.S. |last9=Shinde |first9=S.K. |last10=Sriramachari |first10=S. |date=1988 |title=Gas chromatographic studies of the carbamylation of haemoglobin by methyl isocyanate in rats and rabbits |journal=Journal of Chromatography B: Biomedical Sciences and Applications |volume=426 |issue=2 |pages=239–247 |pmid=3392138 |issn=0378-4347 |doi=10.1016/s0378-4347(00)81952-0}}</ref>