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Perfluorinated Chemical: Toxicity Research with Animal Models

In the 1980s and 1990s, a few laboratory toxicity studies reported liver toxicity and induction of tumors when animals were exposed to perfluorinated chemicals (PFCs). At the turn of the century, a study reported that rodents exposed to PFOS (one type of PFCs) during pregnancy caused stillbirth. Biomonitoring studies also indicated high prevalence of Perfluorinated Chemicals (PFCs) in the blood of workers and the general populations worldwide, as well as in the blood and tissues of wildlife even in the Arctic.

To fully assess the potential human and ecological health risks of these chemicals, EPA conducted research with various laboratory animal models. Exposure to high doses of PFOS in rats and mice during pregnancy caused mortality shortly after birth, likely related to impairment of pulmonary function. At lower doses, newborns survived, but their growth and development were retarded.

Exposure to PFOA in laboratory animal studies did not produce any adverse reproductive or developmental effects, most likely due to the unique ability of the female rats to eliminate this chemical within hours (unlike the males that take weeks). This gender difference in PFOA clearance is absent in humans, rendering the reproductive toxicity data from the rat model difficult to interpret.

Results from a pharmacokinetic study conducted at EPA indicate that both male and female mice eliminated PFOA at about the same rate, making the mouse a more appropriate model for extrapolation to humans. As PFOA body burden built up in the pregnant mice, neonatal mortality (at high doses) and developmental delays (at lower doses) were seen, similar to findings with PFOS. Results generated from these animal studies have been, and will be used as a basis to generate reference doses and health advisory guidelines (for instance, for drinking water and food intake), and support EPA policy (Consent Agreement with industry) and rule-making decisions (Significant New Use Rules).