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Phenobarbital was observed to produce cardiovascular malformations in embryonic chicks. Malformations included simple ventricular septal defect, ventricular septal defect associated with dextroposition of the aorta, double outlet right ventricle, and several types of aortic arch anomalies. Embryos were exposed to phenobarbital at doses of 1-25 mumol on day 4 of incubation (Hamburger-Hamilton developmental stage 24). Doses equal to and greater than 5 mumol phenobarbital (26 mg/kg egg) significantly increased the frequency of embryos with cardiovascular malformations compared with lesser doses and with saline. A significant reduction in heart rate and abnormal rhythm of the heart were observed in embryos treated with teratogenic doses of phenobarbital. No arrhythmia nor significant changes in heart rate were observed in embryos exposed to subteratogenic doses of phenobarbital or to saline.
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