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Effects of prenatal exposure to perfluorooctane sulfonate on the developing lung in the rat
Citation:
Grasty, R. C., N L. Roberts, C S. Lau, B E. Grey, AND J M. Rogers. Effects of prenatal exposure to perfluorooctane sulfonate on the developing lung in the rat. Presented at Teratology Society Meeting, Vancouver, BC, CANADA, June 26, 2004 - July 01, 2007.
Impact/Purpose:
To determine the effects of prenatal exposure to perfluorooctane sulfonate on the developing lung in the rat
Description:
Perfluorooctane sulfonate (PFOS), an environmentally stable industrial and household compound, has been detected in human and wildlife sera. Chronic prenatal exposure to PFOS in rodents leads to mortality in newborns within hours to days after birth. We have demonstrated that treatment on GD 19-20 is sufficient to induce neonatal death in the rat; the underlying pathophysiology remains to be elucidated. Histologically, lungs from these pups appeared immature on postnatal day 0. To further delineate effects on lung development, pregnant Sprague-Dawley rats were treated orally with 0, 25, or 50 mg/kg/d PFOS/K+ on GD 19-20. Time to parturition was not affected. Lungs from newborns (within 1 h after birth) were harvested for morphometric analysis. The proportion of cross-sectional lung area occupied by solid tissue was 0.45 in PFOS-exposed samples (50 mg/kg) vs. 0.34 in controls. The ratio of lung tissue:airway area was also increased in treated animals (0.92 vs. 0.57). Ultrastructural evaluation of the alveolar epithelial cells confirmed the morphometric findings and indicated subcellular disorganization and an increase in stored lamellar bodies in lungs of PFOS-exposed newborns. We are now investigating phospholipid profiles to compare the amount and integrity of surfactant present in lungs from control and treated animals. Additionally, we conducted rescue studies to determine whether the effect of PFOS on lung development could be overcome. Dams were dosed with 0, 25, or 50 mg/kg/d PFOS/K+ (oral gavage) and with 0, 0.2, or 0.5 mg/kg dexamethasone on GD 19-20 to induce alveolar maturation. Pups from control litters experienced 3% mortality by PND 10. All litters exposed to 50 mg/kg PFOS showed 100% mortality. However, the time to death was lengthened in those also receiving dexamethasone. Litters exposed to 25 mg/kg PFOS alone had 19% mortality. The mortality rate was decreased to 9 and 10% in animals treated with 0.2 and 0.5 mg/kg dexamethasone, respectively. These results indicate that exposure to PFOS on GD 19-20 critically impacts normal lung development in the rat, potentially leading to pulmonary dysfunction in the newborns. This abstract does not reflect EPA policy.
Generic template 1.1
16/7/2003