| Perfluorooctanesulfonate (PFOS) is a widely distributed, persistent acid found at low levels in human, wildlife, and environmental media samples. The objectives of the studies described herein were to understand the potential reproductive and developmental effects of PFOS, investigate the cause of neonatal toxicity observed in rat pups born to PFOS-treated dams, evaluate the dose-response of neonatal mortality, and develop an understanding of the relationship of maternal administered dose to maternal internal dose and in utero and lactational transfer of PFOS to fetuses and pups, respectively. In a two-generation study, toxicity was observed in F1 pups, including reduced birth weight, weight gain, and viability at the two highest dose levels, 1.6 and 3.2 mg/kg/day. Results of a follow-up cross-foster study indicated that in utero exposure to PFOS was the primary factor contributing to pup mortality, as opposed to a lack of maternal care in the postnatal period. In a subsequent study, a strong dose-response relationship was demonstrated with respect to neonatal mortality, with decreases in pup survival at maternal dose levels of 0.8 mg/kg/day and higher, reaching statistical significance at 1.6 mg/kg/day. Mechanistic investigations suggest that the observed neonatal mortality is not a result of steroid deficits, and that PFOS does not reduce 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, impair neonatal glycogen utilization, or cause a hypothyroid state in exposed dams or pups. Measurements of PFOS concentrations in biological matrices collected from rat dams, fetuses, and pups during gestation and lactation indicate a linear proportionality of mean maternal serum PFOS concentrations to maternal administered dose prior to mating and through the first two trimesters of gestation. Transfer of PFOS from dam to fetus in-utero was demonstrated, and results suggest that dam and corresponding fetal body burden determine neonatal survival. Transfer of PFOS from dam to pup via milk during lactation was also verified. Serum PFOS levels measured in control dams fostering treated pups suggest transfer of PFOS from pup to dam can also occur, likely though maternal grooming habits and ingestion of urine and feces from the litter. |
