Biomedical Engineering Reference
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mice were killed on GD 7, 8, or 9 in order to examine effects on embryos
following methanol exposure. Remaining pregnant mice were killed on
GD 17 and fetuses were collected for external and skeletal examination.
Imaging techniques including confocal laser scanning and fluorescence
microscopy were used to examine the morphology of fetuses excised at
GD 7, GD 8, and GD 9. Apparent effects of methanol on the embryonic
forebrain included a narrowing of the anterior neural plate, missing
optic vesicles, and holoprosencephaly (Figure 5.3). Fetuses collected
from methanol-treated dams at GD 17 exhibited a range of craniofacial
malformations including facial clefts, anophthalmia, microphthalmia,
varying severities of holoprosencephaly, and gross facial dysgenesis
(Figure 5.4). A total of 15 compound-related skeletal malformations
were tabulated in the report, and these were similar to the skeletal
alterations seen in CD-1 mice (Rogers and Mole, 1997; Connelly and
Rogers, 1997). The craniofacial malformations seen in methanol-
treated CD-1 (exencephaly and cleft palate) were not observed in
the C57BL/6J mice.
5.3.3 Non-Human Primates
Burbacher et al. (1999a, b) carried out toxicokinetic and reproducti-
ve/developmental studies of methanol in Macaca fascicularis monkeys
that were published by the Health Effects Institute (HEI) in a two-part
monograph. Some of the data were subsequently published in the open
scientific literature (Burbacher et al., 2004a, b). Two cohorts of 12
monkeys/group were exposed to low levels (relative to the previously
discussed rodent studies) of 0, 200, 600, or 1800 ppm methanol vapors
for 2.5 hours/day, 7 days/week, during a premating and mating period
(180 days combined) and throughout the entire gestation period
(168 days). The study included an evaluation of maternal reproductive
performance and tests to assess infant postnatal growth and newborn
health, reflexes, behavior, and development of visual, sensorimotor,
cognitive, and social behavioral function. Blood methanol
levels,
clearance, and the appearance of formate were also examined.
With regard to reproductive parameters, there was a statistically
significant decrease in length of pregnancy in all treatment groups.
