NITROFEN DOSE-DEPENDENT GESTATIONAL DAY-SPECIFIC MURINE LUNG HYPOPLASIA AND LEFT-SIDED DIAPHRAGMATIC-HERNIA

2,4-Dichlorophenyl-p-nitrophenyl ether (nitrofen) is known to induce p ulmonary hypoplasia (PH) with or without diaphragmatic hernias (DH) in rats and mice. We determined the timing of administration and dose of nitrofen needed to create left-sided DH and PH in fetal mice. Time-da ted pregnant CD-1 mice were gavaged with various doses of nitrofen in the later one-half of gestational days (GD) 8-11. Fetuses were removed by laparotomy at GD 14, fixed, and evaluated histologically. Fetal lu ng size was inversely related to nitrofen dose. Morphometric analysis of normal and nitrofen-exposed hypoplastic lungs at the pseudoglandula r stage revealed significant differences in lung length, surface area, and in the number of airways. Left-sided DH were observed in a ''dors olateral'' position accompanied by PH in similar to 30% of GD 14 fetus es exposed to 25 mg nitrofen on GD 8. A minimal portion of liver was p resent in the hernia. The lungs of fetuses exposed on GD 9, 10, and 11 progressed to near normal size. Murine fetuses exposed to 25 mg nitro fen on GD 8 resulted in PH and DH, whereas other doses created dose-de pendent PH alone or none at all on GD 11. Our study established that, to create left-sided DH and PH in murine fetuses, nitrofen dose specif icity and time of administration during gestation were crucial.