Teratogenic effects of nitrofen on cellular and functional maturation of the rat lung

The herbicide nitrofen was administered to pregnant Sprague-Dawley and Fischer-344 rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and the effects of maturation of the perinatal lung were evaluated. Nitrofen interfered with the ontogenetic acquisition of lung cells as DNA, RNA, and protein content were subnormal. The hypoplastic lungs in the newborns were associated with structural deficits, resulting in a profound reduction of surface area available for gas exchange and depressed lung compliance. Other factors which influence pulmonary function and systemic delivery of oxygen were also considered. Adrenal catecholamines, which play an important role in surfactant production and fluid resorption in the lung during the transition to air-breathing, were markedly reduced. In addition, red blood cell concentration was significantly diminished. Taken together, these results suggest that the neonatal mortality observed in the nitrofen-treated rats is likely associated with respiratory distress caused by a number of cellular and functional aberrations. These include (a) hypoplasia and structural defects in the lung leading to deficient pulmonary function, (b) deficits in adrenal catecholamines potentially impeding the transition of the lung to air-breathing, and (c) impaired systemic delivery of oxygen due to reduced hemoglobin concentration.