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 1.7.3.3.), formyl-tetrahydrofolate synthetase
(EC 6.3.4.3.) 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
