Clinical and forensic toxicology of methanol.

Methanol has a very simple chemical structure (CH3OH) considering its potential health hazard, including the many poisoning deaths after ingestion. In countries where authentic alcoholic beverages are expensive, restricted, or banned for religious or other reasons, some people resort to purchasing alcoholic drinks made illegally. These clandestine sources of "booze" often contain high concentrations of methanol, added by the perpetrators to enhance potency and increase profits. Although an effective medical treatment for methanol poisoning exists, because most such incidents occur in socially deprived parts of the world, the hospital emergency facilities are scarce and/or inadequate. Trace amounts of methanol (median ~1.0 mg/L) are produced endogenously via certain enzymatic processes, such as one-carbon metabolism. Methanol and methyl esters are also contained in fresh fruits and vegetables as well as in alcoholic beverages. During a period of heavy drinking the blood-methanol concentration (BMC) increases and might surpass 10 mg/L, which is considered a biomarker for alcohol abuse and alcoholism. Methanol itself has a low intrinsic toxicity, but is converted in the body into two highly toxic metabolites, formaldehyde and formic acid. This metabolism is delayed by co-ingestion of ethanol, which creates a latent period of 12-24 h before toxic symptoms develop. Accordingly, when patients are admitted to hospital for diagnosis and treatment, a life-threatening metabolic acidosis has already developed and is irreversible. Symptoms of methanol poisoning include blurred vision, breathlessness, nausea, gastric pains, and acid-base disturbances and deficiency of oxygen in arterial blood. The visual disturbances might even develop into permanent blindness, owing to an interaction of toxic metabolites with the optic nerve. The minimum lethal dose of ethanol in humans is not easy to specify, because most poisonings involve co-ingestion of ethanol, which to some extent protects the patient from toxic sequelae. Effective antidotes for treatment of methanol poisoning are administration of ethanol or the therapeutic drug fomepizole (Antizol®), which is 4-methyl pyrazole (4-MP). Both treatments work by blocking the metabolism of methanol by liver alcohol dehydrogenase (ADH). The metabolic acidosis caused by the accumulation of formic acid in the body is treated with sodium bicarbonate, which helps to normalize pH in the bloodstream. Thereafter, methanol and its metabolites in the blood are removed by hemodialysis. However, the long-term prognosis for survivors of methanol poisoning is not good, because many are elderly males who are in poor health and often suffer from an alcohol-use disorder.