Neonatal death and lung injury in rats caused by intrauterine exposure to O,O,S-trimethylphosphorothioate.

ABSTRACT

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is an impurity present in a number of widely used organophosphorus insecticides and has been recognized as a potent lung toxicant. OOS-TMP was given p.o. to pregnant rats on gestation day (G) 20 at 0.5, 2.5, 10 and 40 mg/kg. Control dams or pair-fed dams (pair-fed to 40 mg/kg) received 2 ml/kg corn oil. Neonates from treated dams died within 72 h after delivery in a dose-related manner 100% at 40 mg/kg, 86% at 10 mg/kg, 15% at 2.5 mg/kg, 1% at 0.5 mg/kg, with 3% in controls and 2% in neonates from pair-fed dams. Neonates from treated (40 or 10 mg/kg) and control dams were cross-fostered. The cross-fostering did not affect mortality of neonates from either dosed dams or from control dams. Disposition of OOS-TMP was studied by using [3H]-OOS-TMP at 0.5, 2.5 and 10 mg/kg. Concentrations of OOS-TMP equivalent in fetal lung were about one half of those in mothers at all doses. In another set of experiments, dams (five dams for each dose) were dosed on G 20 with OOS-TMP p.o. at 0, 0.5, 2.5, 10, and 40 mg/kg or pair-fed (pair-fed to 40 mg/kg) and the fetuses were delivered by cesarean section (C-section) on G 23. In neonates from dams dosed with 10 and 40 mg/kg, cyanosis occurred within 4 h after C-section. Histopathological examination revealed dose-related proliferation of type II pneumocytes in dams and proliferation of interstitial cells and delayed septal/capillary development in neonates.(ABSTRACT TRUNCATED AT 250 WORDS)