Effects of prenatal nitrofen exposure on cardiac structure and function in the rat

The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence intrauterine growth or basal heart rate. In contrast, the herbicide produced a marked depression of heart rate and abnormal electrocardiographic (ECG) profiles in the newborn rats, in conjunction with labored respiratory movements and a profound increase in postnatal mortality. A few animals displayed cardiac ventricular septal defects and diaphragmatic hernias but these malformations did not appear to be associated with the ECG changes. The chronotropic deficiencies seen in the nitrofen-treated pups were reversible by acute hyperoxia (40% oxygen). These results suggest that the teratogenic effects of nitrofen on cardiac physiology and on postnatal mortality cannot be accounted for solely by specific gross anatomical damages to the rat heart and diaphragm; rather, other more subtle morphological and physiological factors which contribute to improper systemic delivery and cellular utilization of oxygen may be involved.