Methanol toxicity

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Methanol toxicity
Other namesMethanol poisoning, methanol overdose
Methanol Lewis.svg
Molecular structure of methanol
Specialty Emergency medicine
Symptoms Decreased level of consciousness, poor coordination, vomiting, abdominal pain, specific smell on the breath [1] [2]
Complications Blindness, kidney failure [1]
Causes Methanol (such as found in windshield washer fluid) [1] [2]
Diagnostic method Blood acidosis, increased osmol gap, methanol blood level [1] [2]
Differential diagnosis Infections, exposure to other toxic alcohols, serotonin syndrome, diabetic ketoacidosis [2]
PreventionConsuming safe alcoholic beverages
Treatment Antidote, hemodialysis [2]
Medication Fomepizole, ethanol [2]
Prognosis Good with early treatment [1]
Frequency1,700 cases per year (US) [3]

Methanol toxicity (also methanol poisoning) is poisoning from methanol, characteristically via ingestion. [1] Symptoms may include a decreased level of consciousness, poor or no coordination, vomiting, abdominal pain, and a specific smell on the breath. [1] [2] Decreased vision may start as early as twelve hours after exposure. [2] Long-term outcomes may include blindness and kidney failure. [1] Blindness may occur after drinking as little as 10 mL; death may occur after drinking quantities over 15 mL (median 100 mL, varies depending on body weight). [1] [4]

Contents

Methanol poisoning most commonly occurs following the drinking of windshield washer fluid. [2] This may be accidental or as part of an attempted suicide. Toxicity may also rarely occur through extensive skin exposure or breathing in fumes. [1] When methanol is broken down by the body it results in formaldehyde, formic acid, and formate which cause much of the toxicity. [2] The diagnosis may be suspected when there is acidosis or an increased osmol gap and confirmed by directly measuring blood levels. [1] [2] Other conditions that can produce similar symptoms include infections, exposure to other toxic alcohols, serotonin syndrome, and diabetic ketoacidosis. [2]

Early treatment increases the chance of a good outcome. Treatment consists of stabilizing the person, followed by the use of 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 damage or a high degree of acidosis. Other treatments may include sodium bicarbonate, folate, and thiamine. [2]

Outbreaks of methanol ingestion have occurred due to contamination of drinking alcohol. This is more common in the developing world. [2] In 2013 more than 1700 cases occurred in the United States. Those affected are usually adult and male. [3] Toxicity to methanol has been described as early as 1856. [5]

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. [6] 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 putaminal hemorrhages, an uncommon but serious complication. [7] [8] 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 pupils with hyperemia of the optic disc and retinal edema.

Cause

Methanol has a moderate to high toxicity in humans. As little as 10 mL of pure methanol when drunk is metabolized into formic acid, which can cause permanent blindness by destruction of the optic nerve. 15 mL is potentially fatal, [1] although the median lethal dose is typically 100 mL (3.4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol). [4] Reference dose for methanol is 0.5 mg/kg/day. [9]

Moonshine distilled from fermented fruit

Although methanol is not produced in toxic amounts by fermentation of sugars from grain starches, [10] it is a major occurrence in fruit spirits. [11] However, in modern times, reducing methanol with the absorption of a molecular sieve is a practical method for production. [12]

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. [13] As a result, ethanol is sometimes denatured (adulterated), and made poisonous, by the addition of methanol. The result is known as methylated spirit, "meths" (British use) or "metho" (Australian slang).[ citation needed ]

This is not to be confused with "meth", a common abbreviation for methamphetamine and for methadone in Britain and the United States.[ citation needed ]

Despite its poisonous content, denatured alcohol is sometimes consumed as a surrogate alcohol.[ citation needed ]

Mechanism

Methanol is toxic by two mechanisms. First, methanol (whether it enters the body by ingestion, inhalation, or absorption through the skin) can be fatal due to its CNS depressant properties in the same manner as ethanol poisoning. Second, in a process of toxication, it is 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. [14] 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. [15] Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, causing hypoxia at the cellular level, and metabolic acidosis, among a variety of other metabolic disturbances. [16]

Treatment

Methanol poisoning can be treated with fomepizole, or if unavailable, ethanol may be used. [14] [17] [18] 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 kidneys without being converted into the very toxic metabolites formaldehyde and formic acid. Alcohol dehydrogenase instead enzymatically converts ethanol to acetaldehyde, a less toxic organic molecule. [14] [19] Additional treatment may include sodium bicarbonate for metabolic acidosis, and hemodialysis or hemodiafiltration to remove methanol and formate from the blood. [14] Folinic acid or folic acid is also administered to enhance the metabolism of formate. [14]

History

There are cases of methanol resistance, such as that of Mike Malloy, whom someone tried and failed to poison by methanol in the early 1930s. [20]

In December 2016, 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, prior to 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. [21]

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 the alcohol could help with the disease. [22] In the United States, the Food and Drug Administration discovered that a number of brands of hand sanitizer manufactured in Mexico during the pandemic contained methanol, and urged the public to avoid using the affected products. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Alcohol (chemistry)</span> Organic compound with at least one hydroxyl (–OH) group

In chemistry, an alcohol, is a type of organic compound that carries at least one hydroxyl functional group bound to a saturated carbon atom. Alcohols range from the simple, like methanol and ethanol, to complex, like sugars and cholesterol. The presence of an OH group strongly modifies the properties of hydrocarbons, conferring hydrophilic (water-loving) properties. The OH group provides a site at which many reactions can occur.

<span class="mw-page-title-main">Ethanol</span> Organic compound (CH₃CH₂OH)

Ethanol is an organic compound with the chemical formula CH3CH2OH. It is an alcohol, with its formula also written as C2H5OH, C2H6O or EtOH, where Et stands for ethyl. Ethanol is a volatile, flammable, colorless liquid with a characteristic wine-like odor and pungent taste. In nature, grape-sugar breaks up by the action of fermentation into alcohol or carbonic acid, without anything being added. As a psychoactive depressant, it is the active ingredient in alcoholic beverages, and the second most consumed drug globally behind caffeine.

<span class="mw-page-title-main">Methanol</span> CH3OH; simplest possible alcohol

Methanol is an organic chemical compound and the simplest aliphatic alcohol, with the chemical formula CH3OH. It is a light, volatile, colorless and flammable liquid with a distinctive alcoholic odor similar to that of ethanol, but is more acutely toxic than the latter. Methanol acquired the name wood alcohol because it was once produced chiefly by the destructive distillation of wood. Today, methanol is mainly produced industrially by hydrogenation of carbon monoxide.

Acetaldehyde is an organic chemical compound with the formula CH3CH=O, sometimes abbreviated as MeCH=O. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

<span class="mw-page-title-main">Alcohol dehydrogenase</span> Group of dehydrogenase enzymes

Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

<span class="mw-page-title-main">Alcoholic ketoacidosis</span> Medical condition

Alcoholic ketoacidosis (AKA) is a specific group of symptoms and metabolic state related to alcohol use. Symptoms often include abdominal pain, vomiting, agitation, a fast respiratory rate, and a specific "fruity" smell. Consciousness is generally normal. Complications may include sudden death.

Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis. Different classes of enzymes, such as P450 monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver.

<span class="mw-page-title-main">Diethylene glycol</span> Chemical compound

Diethylene glycol (DEG) is an organic compound with the formula (HOCH2CH2)2O. It is a colorless, practically odorless, and hygroscopic liquid with a sweetish taste. It is a four carbon dimer of ethylene glycol. It is miscible in water, alcohol, ether, acetone, and ethylene glycol. DEG is a widely used solvent. It can be a normal ingredient in various consumer products, and it can be a contaminant. DEG has also been misused to sweeten wine and beer, and to viscosify oral and topical pharmaceutical products. Its use has resulted in many epidemics of poisoning since the early 20th century.

<span class="mw-page-title-main">Fomepizole</span> Medication

Fomepizole, also known as 4-methylpyrazole, is a medication used to treat methanol and ethylene glycol poisoning. It may be used alone or together with hemodialysis. It is given by injection into a vein.

In clinical chemistry, the osmol gap is the difference between measured blood serum osmolality and calculated serum osmolality.

<span class="mw-page-title-main">Hangover</span> Discomfort following alcohol consumption

A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical symptoms of a hangover may include headache, drowsiness, concentration problems, dry mouth, dizziness, fatigue, gastrointestinal distress, absence of hunger, light sensitivity, depression, sweating, hyper-excitability, irritability, and anxiety.

Ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. Early symptoms include intoxication, vomiting and abdominal pain. Later symptoms may include a decreased level of consciousness, headache, and seizures. Long term outcomes may include kidney failure and brain damage. Toxicity and death may occur after drinking even in a small amount as ethylene glycol is more toxic than other diols.

<span class="mw-page-title-main">High anion gap metabolic acidosis</span> Medical condition

High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap. Metabolic acidosis occurs when the body produces too much acid, or when the kidneys are not removing enough acid from the body. Several types of metabolic acidosis occur, grouped by their influence on the anion gap.

Isopropyl alcohol is a colorless, flammable, organic compound with a pungent alcoholic odor.

<span class="mw-page-title-main">Coprine</span> Chemical compound

Coprine is a mycotoxin. It was first isolated from common inkcap. It occurs in mushrooms in the genera Coprinopsis. When combined with alcohol, it causes "Coprinus syndrome". It inhibits the enzyme aldehyde dehydrogenase, which is involved in the metabolism of alcohol. This inhibition leads to a buildup of acetaldehyde, causing an alcohol flush reaction. Because of this, the mushroom is commonly referred to as Tippler's Bane.

<span class="mw-page-title-main">Jeffrey Brent</span> Medical toxicologist

Jeffrey A. Brent is a medical toxicologist who is a distinguished clinical professor of medicine and emergency medicine at the University of Colorado, School of Medicine. In addition, he is a professor at the Department of Environmental and Occupational Health at the Colorado School of Public Health. He is also the past president of the American Academy of Clinical Toxicology, was editor in chief of the journal Toxicological Reviews, and was a member of the board of directors of the American College of Medical Toxicology. Previously, most of Brent's research focused on the use of fomepizole as a treatment for both methanol and ethylene glycol poisoning, and he led a trial of this drug which resulted in the FDA approving it in December 1997. Currently, Brent serves as Director of the Toxicology Investigators Consortium, an NIH and FDA supported multi center research and surveillance group. Brent is also a senior editor of "Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient," originally published in 2005, and now in its second edition, which was published in 2017.

<span class="mw-page-title-main">Alcohols (medicine)</span> Alcohols used as antiseptics, disinfectants or antidotes

Alcohols, in various forms, are used medically as an antiseptic, disinfectant, and antidote. Alcohols applied to the skin are used to disinfect skin before a needle stick and before surgery. They may also be used as a hand sanitizer; to clean other areas; and in mouthwashes. Taken by mouth or injected into a vein, ethanol is used to treat methanol or ethylene glycol toxicity when fomepizole is not available.

<span class="mw-page-title-main">Disulfiram-like drug</span> Drug that causes an adverse reaction to alcohol

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References

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  5. ↑ Clary JJ (2013). The Toxicology of Methanol. John Wiley & Sons. p. 3.4.1. ISBN   9781118353103. Archived from the original on 2017-09-08.
  6. ↑ National Institute for Occupational Safety and Health (22 August 2008). "The Emergency Response Safety and Health Database: Methanol". Archived from the original on 23 April 2009. Retrieved 17 March 2009.
  7. ↑ 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
  8. ↑ Permpalung N, Cheungpasitporn W, Chongnarungsin D, Hodgdon TM (Oct 2013). "Bilateral putaminal hemorrhages: serious complication of methanol intoxication". N Am J Med Sci. 5 (10): 623–4. doi: 10.4103/1947-2714.120804 . PMC   3842708 . PMID   24350079.
  9. ↑ Methanol (CASRN 67-56-1) Archived 2012-12-05 at the Wayback Machine
  10. ↑ "Distillation: Some Purity Considerations". Moonshine Still. Retrieved 5 May 2015.
  11. ↑ Blumenthal, P; Steger, MC; Einfalt, D; Rieke-Zapp, J; Quintanilla Bellucci, A; Sommerfeld, K; Schwarz, S; Lachenmeier, DW (28 April 2021). "Methanol Mitigation during Manufacturing of Fruit Spirits with Special Consideration of Novel Coffee Cherry Spirits". Molecules. 26 (9): 2585. doi: 10.3390/molecules26092585 . PMC   8125215 . PMID   33925245.
  12. ↑ Hui-Ling Ma; Xiu-Ping Yang; Ying Zuo (15 April 2006). "Study on Method of Decreasing Methanol in Apple Pomace Spirit". Food Science. 27 (4): 138–142.
  13. ↑ Wade, Leroy G. "Physical properties of alcohols". Britannica. Retrieved 2024-08-18.
  14. 1 2 3 4 5 Schep LJ, Slaughter RJ, Vale JA, Beasley DM (2009). "A seaman with blindness and confusion". BMJ . 339: b3929. doi:10.1136/bmj.b3929. PMID   19793790. S2CID   6367081. Archived from the original on 2009-10-08.
  15. ↑ McMartin KE, Martin-Amat G, Noker PE, Tephly TR (1979). "Lack of a role for formaldehyde in methanol poisoning in the monkey". Biochem. Pharmacol. 28 (5): 645–9. doi:10.1016/0006-2952(79)90149-7. PMID   109089.
  16. ↑ Liesivuori J, Savolainen H (September 1991). "Methanol and formic acid toxicity: biochemical mechanisms". Pharmacol. Toxicol. 69 (3): 157–63. doi:10.1111/j.1600-0773.1991.tb01290.x. PMID   1665561.
  17. ↑ Casavant MJ (January 2001). "Fomepizole in the treatment of poisoning". Pediatrics. 107 (1): 170. doi:10.1542/peds.107.1.170. PMID   11134450. Archived from the original on 2005-06-29.
  18. ↑ Brent J (May 2009). "Fomepizole for ethylene glycol and methanol poisoning". The New England Journal of Medicine. 360 (21): 2216–2223. doi:10.1056/NEJMct0806112. PMID   19458366.
  19. ↑ Voet D, Voet JG, Pratt CW (2008). Fundamentals of Biochemistry: Life at the Molecular Level (5th ed.). Hoboken, NJ: Wiley.
  20. ↑ 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.
  21. ↑ Isachenkov V (19 December 2016). "Alcohol poisoning death toll in Russian city rises to 49". Associated Press . Archived from the original on 20 December 2016. Retrieved 19 December 2016.
  22. ↑ Associated Press (27 March 2020). "In Iran, false belief a poison fights virus kills hundreds". Associated Press. Retrieved 27 March 2020.
  23. ↑ "FDA Updates on Hand Sanitizers with Methanol". U.S. Food and Drug Administration. Retrieved 28 July 2020.
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