Methanol Crisis: The Importance of Chemistry and Biology in Today's Society

In recent weeks, a series of poisoning cases has drawn the attention of health authorities in Brazil, particularly in the state of São Paulo. The victims showed symptoms such as dizziness, mental confusion, temporary or permanent loss of vision, and in more severe cases, coma and death. The culprit: methanol.

Although a well-known chemical, methanol continues to appear as a “villain” in episodes of alcoholic beverage adulteration. The good news is that recent advances in chemistry and biology have enabled faster diagnoses and more effective treatments, capable of even reversing some of the most critical poisoning conditions.

What is methanol?

Methanol, also known as methyl alcohol, is the simplest of the known alcohols, with the chemical structure CH3OH. It’s a colorless liquid, relatively volatile, flammable, and highly toxic. Methanol produces a nearly colorless flame due to its ease of complete combustion without soot formation.

Industrially, methanol is widely used as a polar organic solvent, as well as being a raw material for the synthesis of paints, plastics, biodiesel, and various chemical supplies. Biochemically, its toxicity is due to oxidative metabolism in living beings — and comes into action when ingested.

Why is methanol toxic?

When methanol enters the body, it’s recognized as a foreign substance and undergoes oxidation by liver enzymes. This process mainly involves oxidation reactions, which increase the polarity of molecules, making them more soluble in water and allowing their excretion through sweat or urine, for example.

For methanol, the reactions convert it initially into an aldehyde popularly known as formaldehyde, followed by carboxylic acid and formic acid. Similar reactions occur for ethanol in alcoholic beverages, producing acetaldehyde and acetic acid. Both processes generate metabolites harmful to the body. However, while acetaldehyde is mainly responsible for hangover symptoms, formic acid has more pronounced toxicity and can cause death.

Formic acid acts as an inhibitor of cytochrome-c oxidase, also known as complex IV of the electron transport chain, compromising ATP production. Tissues with high energy demands, such as the optic nerve, are the first to suffer the effects of this intoxication, explaining the loss of vision and other neurological injuries as primary symptoms in methanol poisoning cases. Additionally, formic acid causes a decrease in blood pH (metabolic acidosis), resulting in cardiac and neurological complications.

Methanol Antidotes: How Do They Work?

Formic acid acts as an inhibitor of cytochrome-c oxidase, also known as complex IV of the electron transport chain, compromising ATP production. Tissues with high energy demands, such as the optic nerve, are the first to suffer the effects of this intoxication, explaining the loss of vision and other neurological injuries as primary symptoms in methanol poisoning cases. Additionally, formic acid causes a decrease in blood pH (metabolic acidosis), resulting in cardiac and neurological complications.

The metabolic pathway of alcohols involves two main enzymes responsible for oxidation steps: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). As the name suggests, dehydrogenases are enzymes that remove hydrogen atoms attached to carbon, converting alcohols into aldehydes and subsequently into carboxylic acids. Antidotes developed for methanol poisoning act specifically on ADH, blocking its action.

Nowadays, fomepizole (common name for 4-methylpyrazole, formula C₄H₆N₂) is the most effective available treatment. One of the nitrogen atoms in this molecule coordinates with a zinc (II) ion present at ADH’s active site, inhibiting the enzyme and preventing methanol metabolism. Thus, the alcohol is eliminated from the body without being oxidized to formaldehyde and formic acid, avoiding toxic effects.

A second compound that can also be used is ethanol. For a long time, the mains course of action taken for methanol poisoning was consuming large amounts of alcoholic beverages to “occupy” the ADH enzyme. In this situation, ethanol competes with methanol for the enzyme but, with higher affinity, is metabolized preferentially, giving the body time to excrete the methanol.

In both cases, the treatment should be administered under medical supervision, with constant monitoring of methanol and formic acid levels in the blood. Early diagnosis is critical: the sooner the detection, the greater the chance of avoiding irreversible damage.

Detecting Methanol in Beverage Samples

Methanol is often added to alcoholic beverages during adulteration. Imported drinks are counterfeited by adding commercial alcohol for this purpose, which increases material output and lower the costs. However, commercial ethanol can contain traces of methanol, which is the main source of poisoning. A major challenge in chemistry is to develop reliable and accessible methods to detect its presence. The most notable among them are:

• Chromotropic acid colorimetric test: the methanol is initially oxidized by potassium permanganate, forming formaldehyde. The resulting aldehyde reacts with chromotropic acid, producing an intense violet color, measurable by visible-region spectrophotometry or even visually, as developed by researchers at the UNESP Araraquara Chemistry Institute.
• Near-infrared spectroscopy (NIR): this method involves emitting radiation between 750 and 2000 nm on samples and can even be performed on sealed bottles. The light induces characteristic molecular vibrations, generating spectra comparable to reference standards. The analysis allows quick and non-destructive differentiation between ethanol and methanol.

Methanol is often added to alcoholic beverages during adulteration. Imported drinks are counterfeited by adding commercial alcohol for this purpose, which increases material output and lower the costs. However, commercial ethanol can contain traces of methanol, which is the main source of poisoning. A major challenge in chemistry is to develop reliable and accessible methods to detect its presence. The most notable among them are:

As shown, a simple molecule like methanol can have catastrophic impacts on the economy and society, arousing interest in fields such as chemistry and biology. The search for new identification methods and antidotes demands multidisciplinary knowledge, encompassing various domains.

Academic Olympiads, programs like Etapa SigmaCamp, and scientific outreach initiatives play a vital role in sparking young people’s interest in science. It is from this enthusiasm that solutions capable of benefiting the entire society emerge.

In the 2025 edition of Etapa SigmaCamp, we hosted the semi-lab “Dive into the World of Color Chemistry”, led by professors Daniel Rodrigues Cardoso and Antonio Carlos Roveda Jr., both from USP. In this lab, participants could take part in experiments dedicated to food coloring chemistry and how to use chromatography to identify and measure chemical compounds in food.

Therefore, if you are a student passionate about chemistry, science in general, and innovation, Etapa SigmaCamp is an indispensable experience. Subscribe to our newsletter and learn how to join the next edition, scheduled for 2027.