Alcohol is ranked higher than almost all drugs in terms of harm it causes.
Ethanol is thought to cause harm partly as a result of direct damage to DNA caused by its metabolites.
Most significant of the possible long-term effects of ethanol. In addition, in pregnant women it may cause fetal alcohol syndrome.
Ethanol’s toxicity is largely caused by its primary metabolite, acetaldehyde (systematically ethanal) and secondary metabolite, acetic acid. Many primary alcohols are metabolized into aldehydes then to carboxylic acids whose toxicities are similar to acetaldehyde and acetic acid. Metabolite toxicity is reduced in rats fed N-acetylcysteine and thiamine.
Tertiary alcohols cannot be metabolized into aldehydes and as a result they cause no hangover or toxicity through this mechanism.
Some secondary and tertiary alcohols are less poisonous than ethanol, because the liver is unable to metabolize them into toxic by-products. This makes them more suitable for pharmaceutical use as the chronic harms are lower. Ethchlorvynol and tert-amyl alcohol are tertiary alcohols which have seen both medicinal and recreational use.
Other alcohols are substantially more poisonous than ethanol, partly because they take much longer to be metabolized and partly because their metabolism produces substances that are even more toxic. Methanol (wood alcohol), for instance, is oxidized to formaldehyde and then to the poisonous formic acid in the liver by alcohol dehydrogenase and formaldehyde dehydrogenase enzymes, respectively; accumulation of formic acid can lead to blindness or death. Likewise, poisoning due to other alcohols such as ethylene glycol or diethylene glycol are due to their metabolites, which are also produced by alcohol dehydrogenase.
Methanol itself, while poisonous (LD50 5628 mg/kg, oral, rat), has a much weaker sedative effect than ethanol.
Isopropyl alcohol is oxidized to form acetone by alcohol dehydrogenase in the liver, but has occasionally been abused by alcoholics, leading to a range of adverse health effects.