Biomedical Engineering Reference
In-Depth Information
6-12 (e.g., the latest exposure was on GD 12-13) and single-day
exposures were on each of GD 5-9. Peak blood methanol concentration
after a single exposure was about 4mg/ml, and blood levels returned to
baseline within about 24 hours. Two-day exposures on GD 6-7 or 7-8,
and single-day exposure on GD 7 resulted in some fully resorbed litters.
With single-day exposure, the number of resorptions per litter was the
highest on GD 7. The period of susceptibility to methanol-induced cleft
palate was broad, with single exposures on any of gestation days 5-9 or
two-day exposures on GD 6-7 through 11-12 eliciting this effect. Peak
sensitivity to cleft palate occurred with two-day exposure on GD 7-8 or
one-day exposure on GD 7. The basis for this rather early critical period
(induction as early as GD 5) for methanol-induced cleft palate is
unknown at present, but is unusual for an agent with a short biological
half-life. Exencephaly occurred with two-day exposure on GD 6-7
through GD 8-9 (peak GD 6-7) and one-day exposure on GD 5 through
GD 8 (peak GD 7). The peak and breadth of critical periods for skeletal
defects were progressively later going from more anterior to more
posterior structures. Thus, the critical periods were GD 5 for exoccipital
defects, GD 5 or 6 for atlas defects and GD 7 for axis defects, lower
cervical defects, and supernumerary (lumbar) ribs. Single-day exposure
on GD 5 resulted in a significant increase in the incidence of fetuses with
25 presacral vertebrae (26 is normal), while single-day exposure on GD
7 resulted in an increased incidence of fetuses with 27 presacral
vertebrae. The stage-specific patterns of developmental sensitivity to
cleft palate, exencephaly, cervical rib, atlas (vertebra C1) defects, and
axis (vertebra C2) defects following single-day exposures are illustrated
in Figure 5.1.
The skeletal abnormalities observed by Rogers and Mole (1997),
including splits and duplications of the atlas and axis, ribs on cervical
vertebra seven and abnormal number of presacral vertebrae were
suggestive of disruption of embryo segmentation and/or segmental
identity. These skeletal malformations were examined in greater detail
by Connelly and Rogers (1997). Methanol (5 g/kg) was administered
orally to CD-1 mice on GD 7 and fetuses were collected on GD 18.
Anatomical landmarks identifying specific cervical vertebrae were
examined, including the tubercula anterior normally found on cervical
