Prenatal window of susceptibility to perfluorooctane sulfonate‐induced neonatal mortality in the Sprague‐Dawley rat

Abstract

The critical period for increased neonatal mortality induced by perfluorooctane sulfonate (PFOS) exposure was evaluated in the rat. Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 25 mg/kg/d PFOS/K(+) on four consecutive days (gestation days (GD) 2-5, 6-9, 10-13, 14-17, or 17-20) or with 0, 25, or 50 mg/kg/d PFOS/K(+) on GD 19-20. Controls received vehicle (10 ml/kg 0.5% Tween-20) on these days. Maternal weight gain was reduced in treated animals during dosing, as were food and water consumption. Following a 4-day treatment, litter size at birth was unaffected while pup weight was similarly reduced in the three earliest PFOS groups. All PFOS groups experienced decreases in survival while controls remained near 100%. Neonatal survival decreased in groups dosed later during gestation, approaching 100% with dosing on GD 17-20. Most deaths occurred before postnatal day (PND) 4, with the majority in the first 24 hours. Maternal serum PFOS levels on GD 21 were higher in groups exhibiting higher mortality. Following a 2-day treatment, PFOS groups experienced significant pup mortality by PND 1. Neonatal mortality continued through PND 5, when survival was 98, 66, and 3% for the 0, 25, and 50 mg/kg groups, respectively. Pup weight was reduced in treated groups with surviving litters. Gross dissection and histological examination of lungs revealed differences in maturation between control and treated animals on PND 0. We conclude that exposure to PFOS late in gestation is sufficient to induce 100% pup mortality and that inhibition of lung maturation may be involved.

Mixing of perfluorooctanesulfonic acid (PFOS) potassium salt with dipalmitoyl phosphatidylcholine (DPPC)

“…A similar linear decrease of the main phase transition temperature and an increase of peak width have been observed for mixtures of DPPC with increasing mole fraction of several sodium alkylsulfates (C [8][9][10][11][12] ), surfactants which have a headgroup similar to the PFOS potassium salt [21]. These changes in the phase behavior of DPPC-sodium alkylsulfate systems depended only on the concentration of the alkylsulfate surfactant but not on its chain length.…”

“…For example, this direct impairment of pulmonary surfactant may be a contributing factor in the impaired lung function reported in postnatal animal studies and at least partly explain the neonatal mortality observed in these studies [9,10]. Further studies are therefore warranted to fully understand the direct effect of PFOS on structure and function of biological lipid assemblies, especially pulmonary surfactant.…”

“…In contrast to these perinatal teratological studies, postnatal studies in both rats and mice showed a drastic, dose-dependent effect of maternal PFOS exposure on the survival of the neonates immediately after birth [6,[8][9][10]. In particular, neonates from dams exposed to high levels of PFOS during gestation became moribund shortly after birth and did not survive for longer periods of time.…”

“…The critical period for the increased neonatal mortality are the late-gestational, i.e. gestation day 19 and 20 [10], and early postnatal periods [9]. These finding suggests that PFOS may alter lung maturation and function at birth, thus causing neonatal mortality.…”

Effects of 8-2 Fluorotelomer Alcohol on Oleic Acid Formation in the Liver of Rats

“…This compound has been revealed to posses undesirable toxic characteristics such as weight loss, hepatocellular hypertrophy and lipid vacuolation, reduction of serum cholesterol and thyroid hormones, increase in neonatal mortality, and disturbance of neuroendocrine. [16][17][18][19] On the other hand, 8-2 fluorotelomer alcohol is widely utilized, and the global production of 8-2 fluorotelomer alcohol is estimated to be 5ϫ10 6 kg/year during the period 2000-2002. 20) This may make one suppose the increase in the risk of human exposure to this chemical.…”