Methanol toxicity

{{Short description|Medical condition (poisoning)}} {{Infobox medical condition (new) | name = Methanol toxicity | image = Methanol Lewis.svg | alt = | caption = Molecular structure of [[methanol]] | synonym = Methanol poisoning, methanol overdose | pronounce = | field = [[Emergency medicine]], [[toxicology]] | symptoms = [[Decreased level of consciousness]], [[ataxia]], [[vomiting]], [[abdominal pain]], specific smell on the breath<ref name=Kr2012/><ref name=EM2016/> | complications = [[Blindness]], [[kidney failure]], [[death]]<ref name=Kr2012>{{cite journal | vauthors = Kruse JA | title = Methanol and ethylene glycol intoxication | journal = Critical Care Clinics | volume = 28 | issue = 4 | pages = 661–711 | date = October 2012 | pmid = 22998995 | doi = 10.1016/j.ccc.2012.07.002 }}</ref> | onset = | duration = | types = | causes = [[Methanol]] (such as found in [[windshield washer fluid]])<ref name=Kr2012/><ref name=EM2016/> | risks = | diagnosis = Blood [[acidosis]], increased [[osmol gap]], methanol blood level<ref name=Kr2012/><ref name=EM2016/> | differential = [[Infections]], exposure to other [[toxic alcohol]]s, [[serotonin syndrome]], [[diabetic ketoacidosis]]<ref name=EM2016/> | prevention = Consuming safe alcoholic beverages | treatment = [[Antidote]], [[hemodialysis]]<ref name=EM2016/> | medication = [[Fomepizole]], [[ethanol]]<ref name=EM2016/> | prognosis = Good with early treatment<ref name=Kr2012/> | frequency = 1,700 cases per year (US)<ref name=Fer2016/> | deaths = }}

'''Methanol toxicity''' (also '''methanol poisoning''') is [[poisoning]] from [[methanol]], characteristically via ingestion.<ref name=Kr2012/> Symptoms may include an [[Altered level of consciousness|altered/decreased level of consciousness]], poor or no coordination, [[vomiting]], [[abdominal pain]], and a specific smell on the breath.<ref name=Kr2012/><ref name=EM2016/> [[Decreased vision]] may start as early as twelve hours after exposure.<ref name=EM2016/> Long-term outcomes may include blindness and [[kidney failure]].<ref name=Kr2012/> Ingestion of as little as 3.16 grams of methanol can cause irreversible [[Toxic and nutritional optic neuropathy|optic nerve damage]], and the oral [[LD50]] for humans is estimated to be 56.2 grams of pure methanol.<ref name="Moon">{{cite journal |title=Estimations of the lethal and exposure doses for representative methanol symptoms in humans|year=2017 |pmc=5625597 |last1=Moon |first1=C. S. |journal=Annals of Occupational and Environmental Medicine |volume=29 |article-number=44 |doi=10.1186/s40557-017-0197-5 |pmid=29026612 |doi-access=free }}</ref>

Methanol poisoning most commonly occurs following the drinking of tainted [[alcoholic beverage]]s made with [[windshield washer fluid]].<ref name=EM2016/> This may be accidental or as part of an [[suicide|attempted suicide]]. [[Toxicity]] may also rarely occur through extensive skin exposure or breathing in fumes.<ref name="Kr2012" /> When the body breaks down methanol it results in the creation of metabolite byproducts such as [[formaldehyde]], [[formic acid]], and [[formate]] which cause much of the toxicity.<ref name="EM2016" /> The diagnosis may be suspected when there is [[acidosis]] or an increased [[osmol gap]] and confirmed by directly measuring blood levels.<ref name="Kr2012" /><ref name="EM2016" /> Other conditions that can produce similar symptoms include [[infections]], exposure to other [[toxic alcohol]]s, [[serotonin syndrome]], and [[diabetic ketoacidosis]].<ref name=EM2016/>

Early treatment increases the chance of a good outcome. Treatment consists of stabilizing the person and using an [[antidote]]. The preferred antidote is [[fomepizole]], with [[ethanol]] used if this is not available. [[Hemodialysis]] may also be used in those where there is [[organ (anatomy)|organ]] damage or a high degree of [[acidosis]]. Other treatments may include [[sodium bicarbonate]], [[folate]], and [[thiamine]].<ref name=EM2016/>

Oral methanol toxicity is more common in the [[developing world]].<ref name=EM2016>{{cite journal | vauthors = Beauchamp GA, Valento M | title = Toxic Alcohol Ingestion: Prompt Recognition And Management In The Emergency Department | journal = Emergency Medicine Practice | volume = 18 | issue = 9 | pages = 1–20 | date = September 2016 | pmid = 27538060 }}</ref> In 2013 more than 1700 cases occurred in the United States. Those affected are usually adults and males.<ref name=Fer2016>{{cite book| vauthors = Ferri FF |title=Ferri's Clinical Advisor 2017: 5 Books in 1|date=2016|publisher=Elsevier Health Sciences|isbn=978-0-323-44838-3|page=794|url=https://books.google.com/books?id=rRhCDAAAQBAJ&pg=PA794|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908221935/https://books.google.com/books?id=rRhCDAAAQBAJ&pg=PA794|archive-date=2017-09-08}}</ref> Toxicity to methanol has been described as early as 1856.<ref>{{cite book| vauthors = Clary JJ |title=The Toxicology of Methanol|date=2013|publisher=John Wiley & Sons|isbn=978-1-118-35310-3|page=3.4.1|url=https://books.google.com/books?id=xSs8oDQV4uYC&pg=PT44|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908221935/https://books.google.com/books?id=xSs8oDQV4uYC&pg=PT44|archive-date=2017-09-08}}</ref>

==Signs and symptoms== The initial symptoms of methanol intoxication include [[central nervous system depression]], headache, dizziness, nausea, lack of coordination, and confusion. Sufficiently large doses cause unconsciousness and death. The initial symptoms of methanol exposure are usually less severe than the symptoms from the ingestion of a similar quantity of ethanol.<ref name=ershdb>{{cite web| last = National Institute for Occupational Safety and Health| title = The Emergency Response Safety and Health Database: Methanol| date = 22 August 2008| url = https://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750029.html| access-date = 17 March 2009| url-status = live| archive-url = https://web.archive.org/web/20090423005724/http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750029.html| archive-date = 23 April 2009}}</ref> Once the initial symptoms have passed, a second set of symptoms arises, from 10 to as many as 30 hours after the initial exposure, that may include blurring, [[photophobia]], snowstorm vision or complete loss of vision, [[acidosis]], and [[putamen|putaminal]] hemorrhages, an uncommon but serious complication.<ref>Jafarizadeh, A., Homaie, M., Abdollahi, M., & Niyousha, M. (2023). Time course study of optical coherence tomography angiography in patients with methanol-induced optic neuropathy. BMC ophthalmology, 23(1), 178. https://doi.org/10.1186/s12886-023-02937-x</ref><ref>{{cite journal |vauthors=Permpalung N, Cheungpasitporn W, Chongnarungsin D, Hodgdon TM |title=Bilateral putaminal hemorrhages: serious complication of methanol intoxication|journal=N Am J Med Sci|volume=5 |issue=10 |pages=623–4 |date=Oct 2013 |pmid=24350079 |doi=10.4103/1947-2714.120804 |pmc=3842708 |doi-access=free }}</ref> These symptoms result from the accumulation of toxic levels of [[formate]] in the blood, and may progress to death by [[respiratory failure]]. Physical examination may show [[tachypnea]], and eye examination may show dilated [[pupil]]s with [[hyperemia]] of the optic disc and [[retina]]l [[edema]].

==Cause== Ingestion of as little as 4–15 mL of methanol has reportedly caused irreversible [[Toxic and nutritional optic neuropathy|optic nerve damage]], and the oral [[LD50]] for humans is estimated to be 56.2 grams of pure methanol.<ref name="Moon" /> The toxicity is attenuated (not removed) when methanol is ingested with ethanol (such as in the case of tainted drinks), increasing the doses required for symptoms and death.<ref name="Moon"/><ref>{{cite journal | url=https://academic.oup.com/ajhp/article-abstract/38/7/1024/5200360 | doi=10.1093/ajhp/38.7.1024 | title=Oral ethanol doses in patients with methanol poisoning | date=1981 | last1=Peterson | first1=Charles D. | journal=American Journal of Health-System Pharmacy | volume=38 | issue=7 | pages=1024–1027 | url-access=subscription }}</ref> The [[reference dose]] for methanol is 0.5 mg/kg/day.<ref>[http://www.epa.gov/iris/subst/0305.htm Methanol (CASRN 67-56-1)] {{webarchive|url=https://web.archive.org/web/20121205004930/http://www.epa.gov/iris/subst/0305.htm |date=2012-12-05 }}</ref>

[[Methanol]] is not produced in toxic amounts by fermentation of agricultural products or by subsequent distillation.<ref>{{Cite web|url=http://www.moonshine-still.com/page7.htm|title=Distillation: Some Purity Considerations|website=Moonshine Still|access-date=5 May 2015}}</ref> However, in modern times, in order to comply with regulations reducing the methanol amount is sometimes desired.<ref>{{cite journal |last1=Blumenthal |first1=P |last2=Steger |first2=MC |last3=Einfalt |first3=D |last4=Rieke-Zapp |first4=J |last5=Quintanilla Bellucci |first5=A |last6=Sommerfeld |first6=K |last7=Schwarz |first7=S |last8=Lachenmeier |first8=DW |title=Methanol Mitigation during Manufacturing of Fruit Spirits with Special Consideration of Novel Coffee Cherry Spirits. |journal=Molecules |date=28 April 2021 |volume=26 |issue=9 |page=2585 |doi=10.3390/molecules26092585 |doi-access=free |pmid=33925245 |pmc=8125215}}</ref> This can be achieved with the use of a [[molecular sieve]].<ref>{{cite journal|url=http://www.spkx.net.cn/EN/abstract/abstract15544.shtml|title=Study on Method of Decreasing Methanol in Apple Pomace Spirit|journal=Food Science |author=Hui-Ling Ma |author2=Xiu-Ping Yang |author3=Ying Zuo |date=15 April 2006 |volume=27|issue=4|pages=138–142}}</ref>

===Surrogate alcohol=== {{See also|Surrogate alcohol}} Because of its similarities in both appearance and odor to [[ethanol]] (the alcohol in beverages) or [[isopropyl alcohol]], it is difficult to differentiate between the three.<ref>{{Cite encyclopedia |last=Wade |first=Leroy G. |title=Physical properties of alcohols |url=https://www.britannica.com/science/alcohol/Physical-properties-of-alcohols |access-date=2024-08-18 |encyclopedia=Britannica |language=en}}</ref> As a result, ethanol is sometimes [[denatured alcohol|denatured]] (adulterated), and made poisonous, by the addition of methanol. The result is known as methylated spirit, "meths" ([[British English|British]] use) or "metho" ([[Australian English|Australian]] slang).<ref>{{cite web | url=https://healthinfonet.ecu.edu.au/key-resources/resources/27191/?title=Metho++methylated+spirits+++It+s+not+a+drink+&contenttypeid=1&contentid=27191_1 | title=Resources - Promote and practice }}</ref>

Despite its poisonous content, denatured alcohol is sometimes consumed as a [[surrogate alcohol]].<ref>{{cite news |date=19 December 2016 |title=Alcohol poisoning death toll in Russian city rises to 49 |url=https://www.apnews.com/c0c419587e7d44ec8a6c6ac2685b8f2a/Alcohol-poisoning-death-toll-in-Russian-city-rises-to-48 |url-status=live |archive-url=https://web.archive.org/web/20161220183656/https://www.apnews.com/c0c419587e7d44ec8a6c6ac2685b8f2a/Alcohol-poisoning-death-toll-in-Russian-city-rises-to-48 |archive-date=20 December 2016 |access-date=19 December 2016 |newspaper=[[Associated Press]] |vauthors=Isachenkov V}}</ref><ref>Blum D (2010). ''The Poisoner's Handbook: murder and the birth of forensic medicine in Jazz Age New York''. New York: Penguin Books. p. 231. {{ISBN|978-0-14-311882-4}}.</ref><ref>{{cite news |date=1 July 2025 |title=Methanol poisoning cases from tainted alcohol in Jordan rise to 57, death toll stays at 9 |url=https://en.royanews.tv/news/60866 |newspaper=Roya News}}</ref>

==Mechanism== Methanol is [[toxic]] by two mechanisms. First, methanol (whether it enters the body by [[ingestion]], [[inhalation]], or [[absorption (chemistry)|absorption]] through the skin) can be fatal due to its [[CNS depressant]] properties in the same manner as [[Alcohol intoxication#Acute alcohol poisoning|ethanol poisoning]]. Second, in a process of [[toxication]], it is [[metabolism|metabolized]] to [[formic acid]] (which is present as the formate ion) via [[formaldehyde]] in a process initiated by the [[enzyme]] [[alcohol dehydrogenase]] in the [[liver]].<ref name="Schep">{{cite journal|vauthors=Schep LJ, Slaughter RJ, Vale JA, Beasley DM|title=A seaman with blindness and confusion|journal=[[BMJ]]|volume=339|article-number=b3929|date=2009|url=http://www.bmj.com/cgi/content/full/339/sep30_1/b3929|doi=10.1136/bmj.b3929|pmid=19793790|s2cid=6367081|url-status=live|archive-url=https://web.archive.org/web/20091008081309/http://www.bmj.com/cgi/content/full/339/sep30_1/b3929|archive-date=2009-10-08|url-access=subscription}}</ref> Methanol is converted to formaldehyde via alcohol dehydrogenase and formaldehyde is converted to formic acid (formate) via [[aldehyde dehydrogenase]]. The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining.<ref name=noCHOH>{{Cite journal |vauthors=McMartin KE, Martin-Amat G, Noker PE, Tephly TR |title=Lack of a role for formaldehyde in methanol poisoning in the monkey |journal=Biochem. Pharmacol. |volume=28 |issue=5 |pages=645–9 |year=1979 |pmid=109089 |doi= 10.1016/0006-2952(79)90149-7}}</ref> Formate is toxic because it inhibits mitochondrial [[cytochrome c oxidase]], causing [[hypoxia (medical)|hypoxia]] at the cellular level, and [[metabolic acidosis]], among a variety of other metabolic disturbances.<ref>{{Cite journal |vauthors=Liesivuori J, Savolainen H |title=Methanol and formic acid toxicity: biochemical mechanisms |journal=Pharmacol. Toxicol. |volume=69 |issue=3 |pages=157–63 |date=September 1991 |pmid=1665561 |doi= 10.1111/j.1600-0773.1991.tb01290.x}}</ref>

==Treatment== Methanol poisoning can be treated with [[fomepizole]] or ethanol.<ref name="Schep"/><ref>{{cite journal | vauthors = Casavant MJ | title = Fomepizole in the treatment of poisoning | journal = Pediatrics | volume = 107 | issue = 1 | page = 170 | date = January 2001 | pmid = 11134450 | doi = 10.1542/peds.107.1.170 | url = http://pediatrics.aappublications.org/cgi/content/full/107/1/170 | url-status = live | archive-url = https://web.archive.org/web/20050629084540/http://pediatrics.aappublications.org/cgi/content/full/107/1/170 | archive-date = 2005-06-29 | url-access = subscription }}</ref><ref name="Brent">{{cite journal | vauthors = Brent J | title = Fomepizole for ethylene glycol and methanol poisoning | journal = The New England Journal of Medicine | volume = 360 | issue = 21 | pages = 2216–2223 | date = May 2009 | pmid = 19458366 | doi = 10.1056/NEJMct0806112 }}</ref> Both drugs act to reduce the action of [[alcohol dehydrogenase]] on methanol by means of [[competitive inhibition]]. [[Ethanol]], the active ingredient in alcoholic beverages, acts as a competitive inhibitor by more effectively binding and saturating the alcohol dehydrogenase enzyme in the liver, thus blocking the binding of methanol. Methanol is excreted by the [[kidney]]s without being converted into the toxic metabolites formaldehyde and formic acid. Alcohol dehydrogenase instead enzymatically converts ethanol to [[acetaldehyde]].<ref name="Schep"/><ref>{{cite book | vauthors = Voet D, Voet JG, Pratt CW | title = Fundamentals of Biochemistry: Life at the Molecular Level | edition = 5th | location = Hoboken, NJ | publisher = Wiley | date = 2008 }}</ref> Additional treatment may include [[sodium bicarbonate]] for metabolic acidosis, and [[hemodialysis]] or [[hemodiafiltration]] to remove methanol and formate from the blood.<ref name="Schep"/> [[Folinic acid]] or [[folic acid]] is also administered to enhance the metabolism of formate.<ref name="Schep"/>

==History== {{see also|List of methanol poisoning incidents}}

There are cases of methanol resistance, such as that of [[Michael Malloy]], whom a group of acquaintances tried and failed to poison with methanol in the early 1930s.<ref>{{cite book | vauthors = Blum D |title=The Poisoner's Handbook: murder and the birth of forensic medicine in Jazz Age New York |date=2010 |location=New York | publisher = Penguin Books |isbn=978-0-14-311882-4 | page = 231 }}</ref>

In December 2016, [[2016 Irkutsk mass methanol poisoning|78 people died in Irkutsk, Russia]], from methanol poisoning after ingesting a [[counterfeit]] body [[lotion]] that was primarily methanol rather than ethanol as labeled. The body lotion, before the event, had been used as a cheap substitute for [[vodka]] by the impoverished people in the region despite warnings on the lotion's bottles that it was not safe for drinking and long-standing problems with alcohol poisoning across the country.<ref>{{cite news |url=https://www.apnews.com/c0c419587e7d44ec8a6c6ac2685b8f2a/Alcohol-poisoning-death-toll-in-Russian-city-rises-to-48 |title=Alcohol poisoning death toll in Russian city rises to 49 | vauthors = Isachenkov V |newspaper=[[Associated Press]] |date=19 December 2016 |access-date=19 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20161220183656/https://www.apnews.com/c0c419587e7d44ec8a6c6ac2685b8f2a/Alcohol-poisoning-death-toll-in-Russian-city-rises-to-48 |archive-date=20 December 2016}}</ref>

During the [[COVID-19 pandemic]], Iranian media reported that nearly 300 people had died and over a thousand became ill due to methanol poisoning in the belief that drinking methanol could help with the disease.<ref>{{cite web |last1=Karimi |first1=Nasser |last2=Gambrell |first2=Jon |title=In Iran, false belief a poison fights virus kills hundreds |url=https://apnews.com/6e04783f95139b5f87a5febe28d72015 |website=Associated Press |date=27 March 2020 |access-date=27 March 2020 |archive-url=https://web.archive.org/web/20200327084828/https://apnews.com/6e04783f95139b5f87a5febe28d72015 |archive-date=27 March 2020 }}</ref> In the United States, the [[Food and Drug Administration]] discovered that several brands of [[hand sanitizer]] manufactured in Mexico during the pandemic contained methanol, and urged the public to avoid using the affected products.<ref>{{cite web|title=FDA Updates on Hand Sanitizers with Methanol|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-methanol|archive-url=https://web.archive.org/web/20200706175026/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-methanol|archive-date=July 6, 2020|website=U.S. Food and Drug Administration|access-date=28 July 2020}}</ref>

In June 2025, 57 people were poisoned by tainted alcoholic beverages in [[Jordan]]. Nine people died from the incident. Jordanian Authorities arrested 12 individuals that are linked to the factory which manufactured the contaminated alcoholic beverages. All 12 were charged with murder and attempted murder.<ref>{{cite news |url=https://en.royanews.tv/news/60866 | title=Methanol poisoning cases from tainted alcohol in Jordan rise to 57, death toll stays at 9 |date=1 July 2025|newspaper=Roya News}}</ref><ref>{{cite news |url=https://en.royanews.tv/news/60872 | title=Twelve charged with murder in Jordan's contaminated alcohol case |date=1 July 2025 |newspaper=Roya News}}</ref>

==See also== *[[Ethylene glycol poisoning]]

==References== {{Reflist}}

== External links == {{Medical resources | ICD10 = {{ICD10|T51.1}} | ICD9 = {{ICD9|E980.9}} | ICDO = | OMIM = | DiseasesDB = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeSH = | GeneReviewsNBK = | GeneReviewsName = | Orphanet = }}

[[Category:Causes of death]] [[Category:Toxicology]] [[Category:Methanol|Toxic]] [[Category:Wikipedia medicine articles ready to translate]] [[Category:Wikipedia emergency medicine articles ready to translate]]