SOURCES

Methanol, or methyl alcohol, is a colorless, nearly flavorless solvent with a specific gravity of approximately 0.80 at 0°C. Methanol is found in automotive products, including windshield washer fluid, gasoline antifreeze, and alternative fuels. It is a common industrial solvent and may be present in household products including paint removers, Sterno, and rubbing alcohol.

TOXIC DOSE

The toxicity of methanol to humans and other primates is well known, but it is considerably less toxic to other mammalian species.^1,2 Methanol is rapidly absorbed from the digestive tract.^1,3 Lethal dermal exposures have been reported in humans and reproduced experimentally in rabbits, monkeys, and rats.^1,4 Human morbidity and mortality have also been reported from respiratory exposure.^5,6 Methanol toxicosis in mammals other than primates is due to direct central nervous system (CNS) depressant effects and is similar to ethanol toxicosis.^1,4 Human toxicosis has been reported at doses as low as 1.25 mL/kg.⁵ However, the toxic oral dose for methanol in dogs is much higher; it is approximately twice that of ethanol.⁴ The oral median lethal dose (LD₅₀) of methanol in dogs is reported to be between 5 and 11.25 mL/kg.^1,4

TOXICOKINETICS AND MECHANISM OF TOXICITY

It is believed that half of the dose of methanol is eliminated by the lungs in dogs.³ A small amount is eliminated unchanged by the kidneys.⁷ The rest is metabolized.

Methanol is oxidized in the liver to formaldehyde.¹ The enzyme responsible for this process varies from species to species. Alcohol dehydrogenase is preponderant in primates, and a catalase peroxidase complex is preponderant in rodents and possibly some other species.^1,4,8,9 Formaldehyde is rapidly oxidized to formic acid by formaldehyde dehydrogenase.⁴ Formic acid is responsible for the delayed clinical signs of methanol toxicosis in humans and other primates.^2,4,8,9 Formic acid causes acidosis directly in primates and causes ocular and CNS lesions through cytochrome oxidase inhibition.^8–12 Formic acid is metabolized relatively rapidly to carbon dioxide and water by an enzyme system that depends on tetrahydrofolate in other species.⁴ Toxicity of methanol is enhanced in folic acid-deficient animals.⁴