With the international emergence of the SARS-CoV-2 virus, the Centers for Disease Control and Prevention (CDC) has updated its infection control guidance to place more emphasis on the use of personal protection equipment (PPE), hand washing, social distancing and alcohol-based hand rubs to prevent the spread of the virus. [1] Alcohol-based hand rubs, such as hand sanitizers, are inexpensive, readily available and easy to use, thereby making them a staple product to have on hand. Most hand sanitizers contain ethyl alcohol (ethanol) or isopropyl alcohol (isopropanol) as active ingredients. These are generally safe when used topically and are known to inactivate the virus at concentrations between 65-90%. [1] A growing need for hand sanitizer products has led to a spike in mass production and a lack of quality control, allowing items with contaminants to reach the market. Substances like methanol, which are normally removed in the ethanol manufacturing process, are left in the products due to haphazard and hasty distilling techniques. [7] Methanol is not an U.S. Food and Drug Administration (FDA) approved ingredient for hand sanitizers and is known to be quite toxic. Due to multiple cases and deaths from the ingestion of these contaminated products, the FDA issued a warning in June 2020 about nine hand sanitizers manufactured by Eskbiochem SA de CV in Mexico that reached the U.S. market. [2] The FDA has now expanded that list to over 75 products. [2] With hand sanitizers becoming increasingly important in preventing transmission of the SARS-CoV-2 virus and an increasing number of products coming to market, it’s essential for healthcare providers to become familiar with the signs and symptoms of methanol toxicity.

Methanol, also known as wood alcohol, has been around for centuries and was used as a component of embalming fluid as far back as ancient Egypt. [5] Methanol is considered a “toxic alcohol,” which refers to alcohols that are not intended for human consumption. Methanol-containing products commonly encountered include windshield washer fluid, gas line antifreeze, solid cooking fuel and photocopying fluid. Methanol can be absorbed via oral, inhalation and dermal routes. Ingestion can occur accidentally with children or intentionally in patients with a history of substance abuse or mental illness, using it as a substitute for alcohol. Dermal absorption can potentially lead to toxicity, but the absorption depends on several factors including the duration of contact, concentration of methanol, amount and the surface area of exposed skin. [4] There is little data showing the effects of chronic dermal exposure of methanol, but case reports identify skin dryness as a result of repeated exposure. [3,4] Another report documents a few patients developing visual disturbances after application of denatured alcohol as hand sanitizer three to five times a week for more than 6 months. [3]

Like ethanol, methanol can cause inebriation and is metabolized by alcohol dehydrogenase (ADH). When absorbed, it is slowly metabolized by ADH to formaldehyde and subsequently by aldehyde dehydrogenase to formic acid (undissociated form) and formate (dissociated form). Both forms act as a mitochondrial toxin that inhibits cytochrome oxidase, producing oxidative phosphorylation interference. [5] The exact mechanism is not well understood, but optic nerve cells and neurons in the basal ganglia appear to be uniquely susceptible, leading to ocular and neurologic toxicity. [5] Ocular toxicity is responsible for visual impairment, often described as “snowfield vision,” and can ultimately progress to blindness. Neurologic toxicity can lead to abnormal mental status, focal deficits, muscle spasms and parkinsonism. [5] Accumulation of formic acid produces end organ damage and is responsible for the anion gap metabolic acidosis seen in these patients. [5]

When evaluating a patient with possible methanol exposure, a methanol level can confirm the presence (although it is not readily available at most institutions). If there is early clinical evidence of a possible methanol exposure (central nervous system depression, high serum osmolarity, and an unexplained osmolal gap), providers should be thinking about treatment with an ADH antagonist such as fomepizole. Fomepizole competitively inhibits ADH, preventing the metabolism of methanol to its toxic metabolites. If fomepizole is not readily available, ethanol can be used instead. Ethanol will compete with methanol for binding to ADH, preventing formation of toxic methanol metabolites. Maintaining a serum ethanol level of at least 100 mg/dL will ensure adequate blockage of methanol metabolite formation. [8] The endpoint of both therapies is the resolution of the unexplained osmolal gap. Adjunctive therapies to ADH inhibition are folate and sodium bicarbonate. Folate offers a theoretical advantage of enhancing the elimination of formate by converting it to carbon dioxide and water, while sodium bicarbonate shifts the equilibrium formation to favor formate, the less harmful mitochondrial toxin. Patients with late evidence of methanol toxicity (new vision deficits, acidosis, seizures) should undergo dialysis. [6]

With the growing list of contaminated hand sanitizers present on the FDA website and the increased use of hand sanitizers due to SARS-CoV-2, understanding the presentation and management of methanol toxicity is key. Your local poison control center is available at 1-800-222-1222 to assist if a health care provider suspects a methanol exposure or to answer any questions regarding other potential exposures.

References

1. Centers for Disease Control and Prevention. Hand Hygiene Recommendations. https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene.html. Accessed August 27, 2020.
2. Center for Drug Evaluation and Research. FDA updates on hand sanitizers consumers should not use. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use. Accessed August 27, 2020.
3. Chan, A., & Chan, T. (2018). Methanol as an Unlisted Ingredient in Supposedly Alcohol-Based Hand Rub Can Pose Serious Health Risk. International journal of environmental research and public health, 15(7), 1440. https://doi.org/10.3390/ijerph15071440
4. Batterman SA, Franzblau A. Time-resolved cutaneous absorption and permeation rates of methanol in human volunteers. Int Arch Occup Environ Health. 1997;70(5):341-351. doi:10.1007/s004200050228
5. Wiener SW. Toxic Alcohols. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed August 27, 2020. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2569&sectionid=210275462
6. Roberts DM, Yates C, Megarbane B, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med. 2015;43(2):461-472. doi:10.1097/CCM.0000000000000708
7. Difford S. Distillation. The science of distillation. Difford’s Guide – the home of discerning drinkers. https://www.diffordsguide.com/encyclopedia/198/bws/distillation-the-science-of-distillation. Published March 27, 2014. Accessed September 1, 2020.
8. Howland M. Ethanol. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed September 15, 2020. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2569&sectionid=210263617