This is a mechanism module, not a specific disease. Do NOT create a "Toxic Alcohol Poisoning" Disease entry. Disorder entries reference individual nodes via conforms_to, for example "toxic_alcohol_adh_bioactivation#Alcohol Dehydrogenase Bioactivation of the Parent Alcohol". Conforming nodes substitute the parent compound, the acid it is oxidized to, and the organ that acid injures.
Scope: the agent must require oxidation by alcohol dehydrogenase before it is toxic. This excludes ethanol itself, whose acute toxicity is largely the parent compound acting on the central nervous system, and it excludes isopropanol, whose metabolite acetone is a depressant rather than an acid. The general review cited at the trigger node draws exactly that line, excluding isopropanol from the metabolite-driven mechanism, so the exclusion is sourced rather than assumed. Formaldehyde is likewise out of scope as a parent: it enters as the aldehyde, so it bypasses the alcohol dehydrogenase step and is oxidized to formate by a glutathione-dependent route instead. It is a near-conformer that shares everything downstream of this module's central effector while skipping the node the module is named for, and it is deliberately not wired here.
The parent compound is described as having latent rather than absent toxicity. Methanol does produce early central nervous system depression before any metabolite accumulates, and the glycols raise the serum osmolal gap while still unmetabolized. The claim of the trigger node is that the organ-destroying toxicity requires metabolism, not that the parent is inert in every respect.
Why the aldehyde step is one node with the acid accumulation rather than its own: the three conformers model it inconsistently. Methanol separates alcohol dehydrogenase oxidation to formaldehyde from the subsequent oxidation to formate; ethylene glycol bundles bioactivation into a single node; diethylene glycol separates 2-hydroxyethoxyacetic acid from diglycolic acid formation. A module node per sub-step would therefore conform cleanly to only one of them. The second oxidation is bound here through its aldehyde dehydrogenase molecular function so the step remains queryable without forcing a node granularity the conformers do not share.
That bundling has a cost worth stating plainly: the node carries a molecular enzyme activity and an organism-level accumulation together, and is tagged `ORGANISM` for the latter. Under the single-value scale discipline, a node that would naturally take two values is a split signal, and this one would. It is kept whole for the conformance reason above, not because the scales agree. If the three conformers are ever normalised to a common granularity, this node should split into the enzymatic oxidation and the resulting acid burden.
Scope note on the acidosis node and its ethylene glycol conformer: that entry's `Glycolic Acid Accumulation and High Anion Gap Metabolic Acidosis` node bundles the acid accumulation with the acidosis, so it spans this module's amplifier and effector nodes and is wired to the effector. The conformance should be read as scoped to the acid-base claim. The bundling predates this module and is not introduced by it.
The acidosis node carries no ontology binding. There is no GO process term for a high anion gap metabolic acidosis, and GO:0030641 regulation of cellular pH is both the wrong scale, being cellular where this is systemic, and absent from the committed term cache. Following the ontology term contract, no term is better than a bad one, and the claim is carried in prose. If a suitable term is identified later this node is the place to add it.
Exposure to a Toxic Alcohol or Glycol with Latent Toxicity
trigger
A toxic alcohol or glycol is ingested, usually as an adulterated beverage, an automotive or industrial fluid, or a contaminated medicine. The parent compound is rapidly absorbed and distributed but is comparatively inert: it raises the serum osmolal gap and may depress the central nervous system, while the organ-destroying toxicity is still latent and requires metabolism. This latency is why these poisonings present late, why an antidote given early works at all, and why the osmolal gap precedes the anion gap.
Downstream
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Alcohol Dehydrogenase Bioactivation of the Parent Alcohol
The absorbed parent alcohol becomes a substrate for alcohol dehydrogenase, which begins the oxidation that creates the toxic species.
Show evidence (3 references)
"The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction."
Review covering the toxic alcohols as a class; no primary experimental system. States the premise of this node and of the module, that harm comes from the metabolites rather than the ingested compound, and draws the scope line this module adopts by excluding isopropanol from that pattern.
"These results indicate that the mechanism for the target organ toxicity results from metabolites of DEG, and not DEG itself nor formation of EG from DEG"
Rat dosing study comparing the parent compound against its metabolites with and without metabolic inhibition. Establishes experimentally that the parent compound is not the toxic species, which is the specific claim this node makes and which a clinical review can only assert.
"The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes."
Practice guideline; no primary experimental system. Graded INDIRECT because it establishes only that the parent compound is absorbed fast, which supports the latency claim by contrast with the delayed clinical presentation rather than by asserting latency directly.
Alcohol Dehydrogenase Bioactivation of the Parent Alcohol
central effector
Alcohol dehydrogenase oxidizes the parent alcohol to its corresponding aldehyde. This is the rate-limiting, disorder-agnostic step of the module and the key conformance target: methanol to formaldehyde, ethylene glycol to glycolaldehyde, diethylene glycol to its aldehyde, all by the same enzyme. It is also the only node in the chain at which the poisoning can be prevented rather than managed, which is why both antidotes act here and why one enzyme inhibitor serves three chemically unrelated ingestions.
Downstream
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Sequential Oxidation to the Toxic Organic Acid Metabolite
The aldehyde produced here is oxidized onward to the organic acid that carries the toxicity.
Show evidence (2 references)
"Methanol is oxidized by alcohol dehydrogenase to formaldehyde."
Practice guideline; no primary experimental system. States the enzymatic step this node represents, naming both the enzyme and the aldehyde product, for the exemplar parent alcohol.
"Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication"
Review covering the toxic alcohols as a class; no primary experimental system. Graded INDIRECT because it is a therapeutic response cited as validation of the mechanism it targets: benefit from inhibiting the enzyme implies the enzyme is on the causal path, which is the inference this node rests on. It is the evidence that the step is shared across more than one parent compound, which a single-agent paper cannot establish.
Competitive Alcohol Dehydrogenase Inhibition (Fomepizole)
Platform:
Small molecule
Fomepizole competitively inhibits alcohol dehydrogenase, so the parent alcohol is not oxidized and the toxic acid is never generated. It is the worked example of this module's drug-target pattern, and the pattern is unusually clean: because the antidote acts at the shared central effector rather than on any agent-specific step, one drug serves parent compounds that are otherwise chemically unrelated. The strength of that claim is not uniform across the three, and the evidence below is graded accordingly. Methanol and ethylene glycol poisoning both have human clinical evidence for the antidote. For diethylene glycol the support is a rat study in which pretreatment blocked metabolite formation and the resulting organ toxicity, plus a single treated case report, so the module asserts the mechanism is shared rather than that clinical efficacy is equally established. Given before the acid has accumulated the drug prevents the disease rather than treating it, which is why the therapeutic window is set by the bioactivation rate and not by the severity on arrival.
Evidence: 1
Competitive Substrate Saturation of Alcohol Dehydrogenase (Ethanol)
Platform:
Small molecule
Ethanol occupies alcohol dehydrogenase as a competing substrate with higher affinity than the toxic alcohols, so it blocks the same node as fomepizole by a different route. It is retained in the module because it is the fallback where fomepizole is unavailable, which is the situation in many of the mass poisonings these agents cause, and because the pair makes the point that the module's target is the enzyme rather than any particular drug.
Extracorporeal Removal of the Parent Alcohol and Its Acid (Hemodialysis)
Platform:
Device
Hemodialysis clears both the unmetabolized parent alcohol and the acid metabolite, and corrects the acidosis at the same time. It is modelled one step downstream of the antidotes because it removes the substrate and the product rather than blocking the enzyme, and it is the intervention that remains useful once bioactivation has already happened, which is the common situation given how late these poisonings present.