Biomedical Engineering Reference
In-Depth Information
Nelson et al., 1985) suggests that mice are the more sensitive species.
Supporting evidence comes from in vitro studies in which rat and mouse
embryos were exposed to methanol in culture (Andrews et al., 1993a).
In the study of Rogers et al. (1993) in which pregnant female CD-1 mice
were exposed to methanol vapors on GD 6-15 at a range of concentra-
tions, fetal effects included an increase in resorptions, fewer live pups,
and increased incidence of exencephaly, cleft palate, and cervical ribs.
The cervical rib effect was the most sensitive indicator of developmen-
tal toxicity from this study, with a NOAEL of 1000 ppm. The gastrula-
tion stage of mouse development was found to be the most sensitive to
methanol (Rogers and Mole, 1997).
In rats, however, the most sensitive developmental effect, as reported
in the NEDO (1987) two-generation inhalation studies, was lower brain
weight at 3, 6, and 8weeks postnatally after exposure of dams and their
litters to 1000 ppm methanol by inhalation during gestation and
throughout lactation. The NOAEL reported in this study was
500 ppm. No such evaluations of the effects of methanol on brain
growth have been done in mice.
In studies by Burbacher and coworkers (Burbacher et al., 1999a, b,
2004a, b), exposure of monkeys (M. fascicularis) to methanol during
premating, mating, and throughout gestation resulted in a shorter period
of gestation in dams exposed to as low as 200 ppm. The shortened
gestation in methanol-exposed groups was largely the result of C-
sections due to maternal distress. Interpretation of these findings is
complicated because gestational age, birth weight, and infant size in all
groups were within normal ranges for M. fascicularis. There was also
evidence that gestational methanol exposure caused neurobehavioral
effects in offspring. However, the findings were not conclusive and the
dose-response was not robust. Thus, there is insufficient evidence to
determine if the primate fetus is more or less sensitive than rodents to
the developmental toxicity of methanol.
Among the findings of the studies reviewed in this chapter that
demonstrate the teratogenicity and developmental neurotoxicity of
methanol, an increase in the incidence of cervical ribs of gestationally
exposed mice at 2000 ppm methanol (Rogers et al., 1993a) and a
decrease in the brain weights of gestationally and lactationally exposed
