Methanol produces toxicity through two mechanisms. First, methanol can be fatal because of its effects on the central nervous system, which act as a central nervous system depressant in the same way as ethanol poisoning. Second, during intoxication, it is metabolized to formic acid (in the form of formate ion) via formaldehyde in a process initiated by alcohol dehydrogenase in the liver. [31] Methanol is converted to formaldehyde by alcohol dehydrogenase (ADH), and formaldehyde is converted to formic acid (formic acid) by aldehyde dehydrogenase (ALDH). The conversion to formate by ALDH proceeds completely with no detectable residual formaldehyde. Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, leading to hypoxia and metabolic acidosis at the cellular level, as well as various other metabolic disturbances.

Outbreaks of methanol poisoning are mainly due to contamination from drinking alcohol. This is more common in developing countries. [34] Despite this, there were more than 1,700 cases in the United States in 2013. Affected individuals are usually adult males. [35] Outcomes may be good with early treatment. The toxicity of methanol was described as early as 1856.

Due to its toxicity, methanol is often used as a denaturing additive for industrial ethanol. The addition of methanol exempts alcohol excise taxes on industrial ethanol (often referred to as "denatured alcohol" or "methylated spirit") in the United States and other countries.

During the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) found that many hand sanitizer products being sold that were labeled as containing ethanol tested positive for methanol contamination. [38] Due to the toxicity of methanol through skin absorption or ingestion, compared with relatively safe ethanol, the FDA ordered the recall of such hand sanitizer products containing methanol and issued an import alert to prevent these products from illegally entering the U.S. market .