Biomedical Engineering Reference
In-Depth Information
undertaken in rats, mice, and non-human primates to elucidate the
potential for methanol to cause developmental toxicity if exposures
occurred during pregnancy and/or the early postnatal period. In this
section, we present the findings of those studies, which include both
structural and behavioral effects of maternal methanol exposure during
pregnancy and in the early postnatal period. Subsequent sections
examine the pathogenesis of observed developmental disorders as
well as the role of methanol metabolism and maternal folate status.
5.3.1 Rats
The effects of inhaled methanol during pregnancy in the rat were first
studied by Nelson et al. (1985). Sprague-Dawley rats were exposed to
5000, 10,000, or 20,000 ppm methanol for 7 h/day. The two lower con-
centrations were administered daily from GD 1 to GD 19, while the
20,000 ppm exposures were administered daily from GD 6 to GD 15.
Blood methanol levels were assessed in nonpregnant females under the
same exposure conditions. Signs of maternal toxicitywere slight andwere
observed only at the highest concentration. Peak blood methanol levels
were approximately1.3, 2.0, and8.7mg/ml after exposure to5000, 10,000,
or 20,000 ppm, respectively. Maternal exposure to 20,000 ppm methanol
resulted in decreased fetal weight and significant increases in external,
visceral, and skeletal malformations. Skeletal malformations were the
most prevalent and included abnormalities of the basicranium and
the vertebra, including an increase in the incidence of fetuses with a rib
on the seventh cervical vertebra. There was also a low incidence
of exencephaly, encephalocele, hydrocephalus, and various anomalies
of the cardiovascular and urinary systems at the highest exposure level. At
10,000 ppm, there were slight, statistically insignificant increases in these
same anomalies, aswell as a significant decrease in fetalweight, so thiswas
determined to be the Lowest Observed Adverse Effect Level (LOAEL).
No maternal or developmental parameters were affected at 5000 ppm
methanol, the No ObservedAdverse Effect Level (NOAEL) for this study.
The New Energy Development Organization of Japan (NEDO) (1987)
sponsored a teratology study in Sprague-Dawley rats that included an
evaluation of postnatal effects in addition to standard prenatal endpoints.
