Editing Methyl isocyanate (section)

=== 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>