Biomedical Engineering Reference
In-Depth Information
than the rat. The NOAEL for teratogenicity in the mouse was 1000 ppm
based on the induction of cervical ribs in methanol exposed mouse
fetuses (Rogers et al., 1993), but no evaluation of possible effects of
maternal methanol exposure on brain growth in the mouse has been
performed.
5.3.5 Pathogenesis of Methanol-Induced Birth Defects
5.3.5.1 Whole Animal Studies
The pathogenesis of methanol-induced
neural tube defects in CD-1 mouse embryos and fetuses was examined
by Bolon et al. (1994). Following maternal exposure to 15,000 ppm
methanol (6 hours/day) on GD 7-9, 15% of fetuses exhibited cephalic
dysraphism on GD 17. The severity of the defects ranged from
encephalocele to exencephaly with or without facial clefting, anen-
cephaly, and holoprosencephaly. Further, microcephaly was observed
among methanol-exposed fetuses without neural tube defects. Embryos
examined on GD 8.5 following maternal methanol exposure
(15,000 ppm) on GD 7-8 had swollen and poorly elevated cephalic
neural folds compared to controls. Reductions in the mitotic indices of
the neuroepithelium (55% reduction) and the underlying mesoderm
(47% reduction) were reported. Additional dams were exposed to
15,000 ppm methanol on GD 7-9 and embryos examined on GD 9.5
and 10.5. The methanol-exposed embryos exhibited delayed rotation,
microcephaly, and edema as well as anterior neural tube patency. Nile
blue sulfate staining of embryos to visualize apoptosis on GD 8.5, 9.5,
or 10.5 revealed no difference in the staining pattern between methanol-
treated and control embryos.
To determine the effects of methanol on cell proliferation and
histological changes in fetuses of treated dams, Degitz et al. (2004a)
used an identical experimental protocol to that of Rogers et al. (2004),
administering 0, 3.4, or 4.9 gmethanol/kg in distilled water i.p. (split
doses, 4 hours apart) to C57BL/6J mice on GD 7. Embryos were
collected at various times on GD 8 and GD 10. Embryos from dams
exposed to 4.9 g/kg methanol on GD 7 exhibited, on GD 8, reductions in
anterior mesenchyme subjacent to the mesencephalon and the base of
the prosencephalon (embryonic forebrain). The optic pits were often
