Which of the following is the primary toxic metabolite of methanol that causes blindness and metabolic acidosis?

Explanation

## Methanol Metabolism and Toxicity ### Metabolic Pathway Methanol undergoes oxidation in two sequential steps: 1. **Methanol → Formaldehyde** (via alcohol dehydrogenase) 2. **Formaldehyde → Formic acid** (via aldehyde dehydrogenase) ### Mechanism of Toxicity **Key Point:** Formic acid is the primary toxic metabolite responsible for methanol poisoning's clinical manifestations. **High-Yield:** Formic acid causes: - Severe metabolic acidosis (anion-gap acidosis) - Inhibition of cytochrome c oxidase in mitochondria - Optic nerve damage → blindness (characteristic finding) - CNS depression and death in severe cases ### Why Formaldehyde Is Not the Answer While formaldehyde is an intermediate metabolite, it is rapidly converted to formic acid. Formic acid accumulates and is the actual culprit causing systemic toxicity and the classic presentation of methanol poisoning (blindness, metabolic acidosis). ### Clinical Pearl **Mnemonic: "FOAM" for Formic acid Optic damage Acidosis Methanol** Formic acid is poorly metabolized and excreted, leading to its accumulation and prolonged toxicity. This is why fomepizole (an alcohol dehydrogenase inhibitor) and ethanol are used as antidotes — they prevent the conversion of methanol to its toxic metabolites. [cite:Parikh Forensic Medicine & Toxicology Ch 19]