Biomedical Engineering Reference
In-Depth Information
of Methanol as a Fuel for Power Station (NEDO, 1986, 1987). The
NEDO studies were a very large undertaking, conducted to evaluate
methanol as a fuel for power stations. Theses reports, which were not
published, reviewed studies of methanol conducted in monkey, rats,
mice, and aquatic species. These inhalation studies included acute,
chronic, carcinogenicity and effects on reproduction and the fetuses.
The first phase of the research was made available in English in a 114-
page summary (NEDO, 1986). The research in monkeys, rats, and mice
were made available in the second summary of 300 pages (NEDO,
1987). There is a great deal of information provided in the summary, in
some cases as much as you would find in many published papers. In
these studies, there was a 24-month inhalation study in rats and a 18-
month inhalation study in mice to assess carcinogenicity of methanol.
Unfortunately, the results of these two inhalation studies were never
published by NEDO in a peer-reviewed journal. A review of these two
old inhalation studies has been recently published (Cruzan, 2009).
In the rat carcinogenic study, exposure was by inhalation for 20 hours
per day, 7 days per week for 2 years with concentrations of methanol of
0, 10, 100, or 1000 ppm. Fischer 344 rats were used, 52/sex per group.
OECD testing guidelines were used, but no indication of GLP was
followed. NEDO collected clinical tests data (urine, hematological and
biochemical), body weight, feed consumption, and organ weights in
addition to macroscopic and histological evaluations of the standard
tissues. Blood methanol was also measured.
No treatment-related effects were observed in clinical tests, body
weight, feed consumption, and organ weights. The lack of effect on
body weight indicates that the top dose may have been below a
maximum tolerated dose (MTD). Survival was 60-80% at termination
(104 weeks). Blood methanol was elevated in the high dose males and
females (M 54 ppm, F 88 ppm), but not at the other lower doses. The
elevation of blood methanol indicates the beginning of saturation of
catalase (600-1000mg/kg), the key enzyme that metabolizes methanol
to formaldehyde in rodents. On the basis of the blood levels reported the
top dose of methanol was close to 600mg/kg body weight.
There was an increase in nodes in the lung of the high dose males
with most of the nodes being papillary adenomas. In male rats lung
