Methanol

Background Information1 

Small amounts of methanol occur naturally in fruits, vegetables and living organisms due to metabolic processes. It can also be manmade. Methanol is a common solvent used to create fuel, antifreeze, inks, resins, dyes, hand sanitizers, and so many other chemicals. It is a metabolite of aspartame, so it is a byproduct of artificially sweetened drinks and foods, however, in these small amounts, methanol is not dangerous.

Methanol Structure High Res Stock Images | Shutterstock

Figure 1. Basic Chemical Properties (Image from Google Images)

Mechanism of Action and Toxicokinetics2,3

Methanol can enter the body through inhalation, ingestion, dermal exposure or eye contact. The main culprit of toxicity is ingestion. Once methanol enters the body, it is quickly absorbed from the gastrointestinal tract and metabolized in the liver. Alcohol dehydrogenase breaks methanol down into formaldehyde which is then further oxidized by aldehyde dehydrogenase to form formic acid and formate. This is illustrated in Figures 2 and 3. A lethal dose of methanol is roughly 1g/kg, but permanent vision damage can happen with as little as 30 mL.

Severe Metabolic Acidosis Secondary to… Methanol Poisoning 4/3/2019 | Santa Clara Valley Medical Center Internal Medicine Residency

Figure 2. MOA and Toxic Effects (Image from Google Images)

Signs and Symptoms of Toxicity2

Acute

Early on after exposure there may not be much for signs or symptoms, but as the methanol continues to be metabolized, the levels of toxicity will increase. The more time that passes from exposure to treatment the more severe the degree of toxicity.

Less than 8 hours post exposure:  drowsiness, reduced level of consciousness, confusion, headache, dizziness, ataxia, nausea, vomiting, blurred vision, visual disturbances, and heart and respiratory failure.

Chronic

Greater than 8 hours post exposure there tend to be more severe effects:  metabolic acidosis, blindness, kidney failure, seizures, coma, and death.

The most common permanent health effect following severe poisoning is blindness, brain damage that could result in difficulty walking/moving, damage to the peripheral nervous system, and encephalopathy.

Target Organs4

Skin
Eyes
Respiratory System
Central Nervous System
GI Tract

Carcinogenicity5

There are no published studies linking methanol exposure to cancer or tumor growth.

Treatments2

Methanol poisoning & Antidote MOA #pharmacology #antidote ... | GrepMed

Figure 3. MOA and Antidote Competition (Image from Google Images)

Effective antidotes are ethanol and Fomepizole. Ethanol is competitive with methanol when binding to alcohol dehydrogenase, so if ethanol can beat out methanol, methanol won’t be metabolized and its toxic metabolites won’t be produced. Similarly, Fomepizole blocks the conversion of methanol to formic acid and prevents acidosis, shown in Figures 2 and 3. This is the preferred method because the therapeutic dose is more easily maintained during treatment. These antidotes are only effective if caught early enough. Once a patient becomes acidotic the best thing to do is hemodialysis and administration of folinic acid (promotes formate metabolism into less toxic chemicals).

Historical or unique exposures

During the COVID-19 pandemic, the use of hand sanitizer skyrocketed. A few companies had their products recalled when it was discovered that they were made with methanol instead of ethanol or isopropanol. This led to some deaths and blindness due to accidental ingestions.

The following case study goes into great detail what happens when methanol is ingested accidentally through making homemade moonshine

References

  1. Skelly, Jimi. “Chemical Safety Facts About Methanol”. Org, 2017, https://www.chemicalsafetyfacts.org/methanol/. Accessed 6 July 2021.
  2. “CDC – The Emergency Response Safety And Health Database: Systemic Agent: METHANOL – NIOSH”. Gov, 2011, https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750029.html. Accessed 6 July 2021.
  3. Ashurst JV, Nappe TM. Methanol Toxicity. [Updated 2020 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482121/
  4. “CDC – NIOSH Pocket Guide To Chemical Hazards -Methyl Alcohol”. Cdc.Gov, 2019, https://www.cdc.gov/niosh/npg/npgd0397.html. Accessed 31 July 2021.
  5. Cruzan, George. “Assessment of the cancer potential of methanol.” Critical reviews in toxicology vol. 39,4 (2009): 347-63. doi:10.1080/10408440802475199