The present study was conducted to determine whether exposure of pregnant F/344 rats to ethylene glycol monobutyl ether during critical periods of cardiovascular development adversely affected the structure of the fetal heart and great vessels. EGBE dissolved in distilled water was administered daily by gavage on either gestational days 9 through 11 at doses of 0. 30. 100 or 200 mg/kg/day or on gd 11 through 13 at doses of 0, 30, 100 or 300 mg/kg/day .
The maternal effects of EGBE given from gd 9 through 11 or from gd 11 through 13 at doses greater than or equal to 100 mg/kg/day included marked reductions in body weight and/or weight gain, increases in organ weights (kidney and spleen) and severe hematotoxicity. In particular, dramatic reductions in circulating red blood cells, hematocrit and hemoglobin resulted by 24 hr after treatment. By gd 20, the hematotoxic effects were nearly reversed. The changes observed in hematological parameters and organ weights in this study are typical of hemolytic anemia and the compensatory hematopoietic response associated with recovery.
Following developmental phase-specific dosing of the dams with EGBE, neither heart nor great vessel defects were observed in fetuses examined near term (gd 20). No other indications of embryo/fetal toxicity were observed at the low and middle doses which were either nontoxic (30 mg/kg/day ) or toxic (100 mg/kg/day ) to the dams. The viability of embryos was markedly reduced by EGBE treatment at 200 mg/kg/day from gd 9 through 11, a dose that also produced severe hematotoxicity as well as general toxicity in the dams.
In conclusion, development of the F/344 rat was not uniquely sensitive to EGBE at 30 or 100 mg/kg/day, po, administered on either gd 9 through 11 or gd 11 through 13. Reduced prenatal viability was noted at 200 mg/kg/day following exposure on gd 9 through 11, but not on gd 11 through 13. Thus, 100 mg/kg/day was the no-observed-adverse-effect level for developmental toxicity in this study. The maternal no-observed-adverse-effect-level was 30 mg/kg/day for both treatment periods.