Explained | How methanol poisoning kills

The story so far: As of 10 pm on May 16, as many as 22 people had died after consuming spurious liquor in Chengalpattu and Villupuram districts of Tamil Nadu while 30 others were still being treated at hospitals. The incidents occurred late last week, barely a month after the state government said that it had brought such deaths under control. They are also tinged with an element of surprise because liquor sales in Tamil Nadu are wholly controlled by the state, with more than 5,300 outlets. Its government is currently in the process of closing 500 outlets.

What is the alcohol in liquor?

Liquor is differentiated by its alcohol content – from the 5% or so of beer to the 12% or so of wine to the 40% or so of distilled spirits (all by volume). In the beverages consumed for recreational purposes, the alcohol in question is almost always ethanol. Technically, in this context, ethanol is a psychoactive drug that, in low doses, reduces the level of neurotransmission in the body, leading to its typical intoxicating effects.

Contrary to popular belief, the World Health Organization has found that “no level of [its] consumption is safe for our health”. Long-term use leads to dependence, heightens the risk of some cancers and heart disease, and may eventually cause death.

Ethanol (C ₂H ₅OH) is one carbon atom bonded to three hydrogen atoms and one more carbon atom; the second carbon atom is also bonded to two hydrogen atoms and the hydroxyl group, a.k.a. the ion OH ^–. Inside the body, it is metabolised in the liver and the stomach by alcohol dehydrogenase (ADH) enzymes to acetaldehyde. Then, aldehyde dehydrogenase (ALDH) enzymes transform the acetaldehyde into acetate.

The adverse effects of alcohol consumption, from the hangover to a cancer, are due to acetaldehyde.

What is spurious liquor?

Spurious liquor is characterised by the liquid mixture containing methanol as well.

The police have thus far determined that the spurious liquor in both the Chengalpattu and the Villupuram incidents arose from the same source, and that arrack sellers had purchased industrial-grade methanol from factories and had sold it to the victims. (Arrack is distilled from the fermented sap of the palm tree.)

In many older cases, such liquor is typically a homemade liquor to which methanol was added to strengthen the intoxicating effects (in colloquial parlance, its kick) and/or to increase its bulk volume.

The Food Safety and Standards (Alcoholic Beverages) Regulations 2018 stipulate the maximum permissible quantity of methanol in different liquors. These values span a wide range, including “absent” in coconut fenny, 50 grams per 100 litres of country liquor, and 300 grams per 100 litres of pot-distilled spirits.

What is methanol?

The methanol molecule (CH ₃OH) consists of one carbon atom bonded with three hydrogen atoms and one hydroxyl group.

Schedule I of the Manufacture, Storage and Import of Hazardous Chemical Rules 1989 includes methanol. The Indian Standard IS 517 applies to how the quality of methanol is to be ascertained and, together with the Tamil Nadu Denatured Spirit, Methyl Alcohol, and Varnish (French Polish) Rules 1959, what signage methanol packaging should carry.

The most common way to produce methanol is to combine carbon monoxide and hydrogen in the presence of copper and zinc oxides as catalysts at 50-100 atm of pressure and 250° C. In the pre-industrial era, but going back to ancient Egypt, people also made methanol (together with several other byproducts) by heating wood to a very high temperature.

Methanol has several industrial applications, including as a precursor to acetic acid, formaldehyde, and aromatic hydrocarbons. It is also used as a solvent and as antifreeze. In Tamil Nadu, the manufacture, export, import, storage, and sale of methanol requires licences under the 1959 Rules.

How does spurious liquor kill?

The deadliness of spurious liquor arises from methanol. James Manor, emeritus professor of Commonwealth Studies at the University of London, wrote in December 2022, “In every hooch tragedy in the history of India – and of the world since 1945 – the poison has been methanol.” The human body contains infinitesimal quantities of methanol (4.5 ppm in the breath of healthy individuals, per a 2006 study) as a result of eating some fruits. But even for an adult, more than 0.1 ml of pure methanol per kilogram of body-weight can be devastating.

Once ingested, methanol is metabolised in the liver by ADH enzymes to form formaldehyde (H-CHO). Then, ALDH enzymes convert formaldehyde to formic acid (HCOOH). The accumulation of formic acid over time leads to a baneful condition called metabolic acidosis. Acidosis can lead to acidemia: when the blood’s pH drops below its normal value of 7.35, becoming increasingly acidic.

The blood’s pH is normally maintained by a balance between an acid, like carbon dioxide, and a base, like the bicarbonate ion (HCO ₃^–). The ‘metabolic’ means the concentration of the bicarbonate ion is dropping, leading to the acid gaining the upper hand.

Formic acid also interferes with an enzyme called cytochrome oxidase, which in turn disrupts cells’ ability to use oxygen and leads to the build-up of lactic acid, contributing to acidosis.

According to a paper published by Archives of Toxicology in January 2022, consuming methanol also leads to “methanol-induced optic neuropathy …, a serious condition that may result in long-term or irreversible visual impairment or even blindness [due to] damage and loss of function of the optic nerve and retina”.

It added that this consequence “shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries.”

Methanol-poisoning can also cause cerebral edema, haemorrhage, and death.

How can methanol-poisoning be treated?

Once methanol is ingested, the body takes some time to completely eliminate it. One estimate suggests that as much as 33% is still left behind after 48 hours. It is completely absorbed via the gastrointestinal tract and the blood-methanol level can reach its maximum value within 90 minutes.

There are two immediate ways to treat methanol poisoning. One is to administer ethanol (of a pharmaceutical grade, by healthcare workers). This may sound counterintuitive but ethanol competes very well with methanol for the ADH enzymes, which metabolise ethanol around 10x faster. As a result, the methanol is kept from being metabolised to formaldehyde.

The other option is to administer an antidote called fomepizole, which has a similar mechanism: it slows the action of the ADH enzymes, causing the body to produce formaldehyde at a rate that the body can quickly excrete, preventing the deadlier effects from kicking in.

Both courses of action are limited by the availability of their characteristic compounds. Fomepizole is expensive whereas pharmaceutical-grade ethanol needs to be administered under supervision.

Healthcare workers may also have the individual undertake a dialysis to remove methanol and formic acid salts from the blood, and mitigate damage to the kidneys and the retina.

They may also administer folinic acid, which encourages the formic acid to break up into carbon dioxide and water.

Both fomepizole and folinic acid are in the WHO’s list of essential medicines.

The formic acid would have begun accumulating in dangerous amounts around 18-24 hours after ingestion, affecting the optic nerve, kidneys, the heart, and the brain. Ophthalmic effects have been observed in 50% of those who have consumed methanol, and they become apparent within 24 hours.

If the individual consumed ethanol along with the methanol, the damage may not be evident until after a few days, further delaying treatment and increasing mortality.

• Spurious liquor is characterised by the liquid mixture containing methanol as well. The police have thus far determined that the spurious liquor in both the Chengalpattu and the Villupuram incidents arose from the same source, and that arrack sellers had purchased industrial-grade methanol from factories and had sold it to the victims.
• In many older cases, such liquor is typically a homemade liquor to which methanol was added to strengthen the intoxicating effects (in colloquial parlance, its kick) and/or to increase its bulk volume.
• Once ingested, methanol is metabolised in the liver by ADH enzymes to form formaldehyde (H-CHO). Then, ALDH enzymes convert formaldehyde to formic acid (HCOOH). The accumulation of formic acid over time leads to a baneful condition called metabolic acidosis. Acidosis can lead to acidemia: when the blood’s pH drops below its normal value of 7.35, becoming increasingly acidic.