Biomedical Engineering Reference
In-Depth Information
Unfortunately, no blood measurements were made in this study.
Blood methanol, and formic acid levels would have been useful. Other
than signs of nasal irritation in rats exposed at 5000 ppm, the results of
this study do not suggest that the top dose of 5000 ppm was toxic to
either rats or monkeys.
It is interesting in the differences in response see in the subacute
NEDO studies (NEDO, 1986, 1987) and the Andrews study (Andrews
et al., 1987). The species of monkey used were the same in both studies.
At the top dose (5000 ppm methanol) in the Andrews study (Andrews
et al., 1987) no treatment-related effects were noted, while in the NEDO
study (NEDO, 1986, 1987), in a range finding study the NOAEL was
3000 ppm methanol and the LOAEL (clinical signs, blood methanol
levels, and blood formic acid levels) was 5000 ppm. One major differ-
ence is the length of exposure in these two studies. In the Andrew study
(1987) exposure was 6 hours per day for 5 days per week for 4 weeks. In
the NEDO study (NEDO, 1986, 1987), exposure was nearly continuous
(21 hour daily for 14 days at 500 ppm and 21 days at 300 ppm). In the
Andrews study there was a much greater likelihood that methanol did
not build up over time, which happened in the NEDO study (see blood
methanol and formic acid levels).
4.5.2 Rats
In the NEDO rat chronic inhalation study, exposure was for 20 hours per
day for 12 months with concentrations of methanol of 0, 10, 100, or
1000 ppm. Fischer 344 rats were used, 20 per sex group. This study
was run at the same time as an 24-month carcinogenicity in rats. The
24-month study is discussed in more detail in Chapter 8 on cancer.
OECD testing guidelines were used, but no indication of GLP was
mentioned. Parameters evaluated included clinical tests data (urine,
hematological, and biochemical endpoints), body weight, feed con-
sumption, survival and organ weights in addition to macroscopic and
histological evaluations of the standard tissues.
No treatment-related effects were observed in clinical parameters,
body weight, feed consumption, survival, histopathological, urinalysis,
biochemical tests, and organ weights at 100 ppm and lower. Slight
