Methanol has a high toxicity in humans. If as little as 10 mL of pure methanol is ingested, for example, it can break down into formic acid, which can cause permanent blindness by destruction of the optic nerve, and 30 mL is potentially fatal,[18] although the median lethal dose is typically 100 mL (4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol[19]). Reference dose for methanol is 0.5 mg/kg/day.[20] Toxic effects take hours to start, and effective antidotes can often prevent permanent damage.[18] Because of its similarities in both appearance and odor to ethanol (the alcohol in beverages), it is difficult to differentiate between the two (such is also the case with denatured alcohol). However, there are cases of methanol resistance, such as that of Mike Malloy, who was the victim of a failed murder attempt by methanol in the early 1930s.[21]
Methanol is toxic by two mechanisms. First, methanol (whether it enters the body by ingestion, inhalation, or absorption through the skin) can be fatal due to its CNS depressant properties in the same manner as ethanol poisoning. Second, in a process of toxication, it is metabolized to formic acid (which is present as the formate ion) via formaldehyde in a process initiated by the enzyme alcohol dehydrogenase in the liver.[22] Methanol is converted to formaldehyde via alcohol dehydrogenase (ADH) and formaldehyde is converted to formic acid (formate) via aldehyde dehydrogenase (ALDH). The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining.[23] Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, causing the symptoms of hypoxia at the cellular level, and also causing metabolic acidosis, among a variety of other metabolic disturbances.[24]
