Dr. Woodrow C. Monte’s Methanol Research – University Of Arizona - Part 4

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The greater toxicity of methanol to man is deeply rooted in the limited biochemical pathways available to humans for detoxification. The loss of uricase (EC, formyl-tetrahydrofolate synthetase (EC and other enzymes during evolution sets man apart from all laboratory animals including the monkey. There is no generally accepted animal model for methanol toxicity. Humans suffer "toxic syndrome" at a minimum lethal dose of < 1 gm/kg, much less than that of monkeys, 3-6 g/kg. The minimum lethal dose of methanol in the rat, rabbit, and dog is 9.5, 7, and 8 g/kg, respectively; ethyl alcohol is more toxic than methanol to these test animals. No human or experimental mammalian studies have been found to evaluate the possible mutagenic, teratogenic or carcinogenic effects of methyl alcohol, though a 3.5% chromosomal aberration rate in testicular tissues of grasshoppers was induced by an injection of methanol.

The United States Environmental Protection Agency in their Multimedia environmental Goads for Environmental Assessment recommends a minimum acute toxicity concentration of methanol in drinking water at 3.9 party per million, with a recommended limit of consumption below 7.8 mg/day. This report clearly indicates that methanol:

"is considered a cumulative poison due to the low rate of excretion once it is absorbed. In the body, methanol is oxidized to formaldehyde and formic acid; both of these metabolites are toxic."

Role of Formaldehyde

Recently the toxic role of formaldehyde (in methanol toxicity) has been questioned. No skeptic can overlook the fact that, metabolically, formaldehyde must be formed as an intermediate to formic acid production. Formaldehyde has a high reactivity which may be why it has not been found in humans or other primates during methanol poisioning. The localized retinal production of formaldehyde from methanol is still thought to be principally responsible fro the optic papillitis and retinal edema always associated with the toxic syndrome in humans. This is an intriguing issue since formaldehyde poisoning alone does not produce retinal damage.

If formaldehyde is produced form methanol and does have a reasonable half life within certain cells in the poisoned organism the chronic toxilogical ramifications could be grave. Formaldehyde is a know carcinogen producing squamous-cell carcinomas by inhalation exposure in experimental animals. The available epidemiological studies do not provide adequate data for assessing the carcinogenicity of formaldehyde in man. However, reaction of formaldehyde with deoxyribonucleic acid (DNA) has resulted in irreversible denaturation that could interfere with DNA replication and result in mutation. Glycerol formal, a condensation product of glycerol and formaldehyde (which may be formed in vivo), is a potent teratogen causing an extremely high incidence of


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