Biomedical Engineering Reference
In-Depth Information
used in animal studies go beyond the lethal dose in humans and the
saturation of catalase, the enzyme that metabolizes methanol to form-
aldehyde in animals. Blood methanol increases dramatically once
catalase is saturated. Methanol is water-soluble so increased methanol
is found throughout the tissues in the body. This is not the case in
humans, where ADH is the primary enzyme in the breakdown of
methanol to formaldehyde. The recent findings (Lu et al., 2012)
demonstrate the formation of a dose-related increase in exogenous
labeled formaldehyde hydroxymethyl DNA adducts derived from
labeled methanol (
13
CD
4
) in rats in multiple tissues at and above the
lethal dose in humans and the dose above the saturation of catalase
suggesting that formaldehyde hydroxymethyl DNA adducts could be a
genotoxic factor in the response in rodent bioassays at high doses.
There is also limited evidence that oxidative damage, at high levels
above the saturation of catalase, may be a contributor to the some of
the responses reported in rat studies. In addition to oxidative damage,
the increase in DNA adducts from high doses of methanol and other
factors, such as infection and misdiagnosis may be responsible for the
reported increase in tumors in some rodent studies. The findings
reported in bioassays, if real, appear to have little relevance to
humans. The fact that the top doses of methanol used in animal
studies, where oxidative damage and DNA adducts formation from
methanol occurs, are seen at higher than the acute lethal dose in
humans and above the saturation of catalase supports that methanol is
unlikely a cancer risk to humans.
REFERENCES
Apaja, M. (1980) Evaluation of toxicity and carcinogenicity of malonalde-
hyde. Acta Univ. Oul. D 55 Anat. Path. Microbiol. 8, 1-59.
Belopoggi, F., Moranndo, M., Filippini, F., and Maltoni, C. (1997) Results
of the long term experimental studies on the carcinogenicity of methyl tert-
butyl ether. Ann. N.Y. Acad. Sci. 837, 77-95.
Campbell, J.A., Howard, D.R., Backer, L.C., and Allen, J.W. (1991) Evidence
that methanol inhalation does not induce chromosome damage in mice.
Mutat. Res. 260, 257-264.
