Effects of the herbicide 2,4-dichlorophenyl- p-nitrophenyl ether (nitrofen) on fetal lung developments in rats

Abstract

We have examined whether the neonatal mortality accompanied by lung hypoplasia and atelectasis induced by prenatal exposure to the diphenyl ether herbicide 2,4-dichlorophenyl- p-nitrophenyl ether (nitrofen) could be due to alterations in pulmonary surfactant synthesis. The specific hypothesis we tested was whether in utero exposure to nitrofen accelerated the catabolic metabolsim of glucocorticoids by induction of mixed function oxidase enzymes, leading to a depression in glucocorticoid levels and delay in fetal lung surfactant synthesis. Hepatic aminopyrine- n-demethylase and aniline hydroxylase activities in the 9000 g supernatant were not elevated in rat dams exposed to 50 mg/kg/day on days 8–18 of pregnancy. Cortisone and corticosterone levels in fetal plasma were not altered by nitrofen exposure. Fetal lung surfactant synthesis was also not affected, as indicated by measurements of total lung phospholipids, [ 14C]choline uptake into lung lipids, and cholinephosphotransferase (CPT) activity. Surface tension values from saline extracts of fetal lungs and fetal plasma corticosterone levels were monotored after co-administration of nitrofen and dexamethasone. Nitrofen exposure alone had no influence on these parameters, while dexamethasone, with or without nitrofen, depressed corticosterone levels and minimum surface tension measurements. These results suggest that the level of glucocorticoids and capacity of the fetal lung to respond to glucocorticoids by synthesizing and releasing surfactant are not affected by prenatal exposure to nitrofen.