Endocrine disrupting properties of perfluorooctanoic acid

Abstract

Perfluoroalkyl acids (PFAAs) have attracted attention in recent years for their environmental ubiquity, as well as their toxicity. Several PFAAs are found in human tissues globally, as humans are exposed on a daily basis through intake of contaminated food, water, and air, irrespective of proximity to industry. Perfluorooctanoic acid (PFOA) is a PFAA shown to be developmentally toxic in mice, with broad and varied health consequences that may include long-lasting effects in reproductive tissues and metabolic reprogramming. To date, the only demonstrated mode of action by which the health effects of PFOA are mediated is via the activation of the peroxisome proliferator-activated receptor alpha (PPARα). The endogenous roles for this receptor, as well as the adverse outcomes of activation by exogenous agents during development, are currently under investigation. Recent studies suggest that PFOA may alter steroid hormone production or act indirectly, via ovarian effects, as a novel means of endocrine disruption. Here we review the existing literature on the known health effects of PFOA in animal models, focusing on sensitive developmental periods. To complement this, we also present epidemiologic health data, with the caveat that these studies largely address only associations between adult exposures and outcomes, rarely focusing on endocrine-specific endpoints, susceptible subpopulations, or windows of sensitivity. Further research in these areas is needed.

Fig. 1

MG development of female offspring in a late-life effects cross-foster study. (A) Whole mount preparations of mammary tissue from female offspring are shown at PND 22 (25×; a lymph node appears as a large darkly staining object), PND 42 (50×), and PND 63 (50×). Glands pictured are representative of mean respective scores (N = 10–13 adult females per treatment group at PND 22, N = 9–18 per group at PND 42, N = 9–17 per group at PND 63). *Significant treatment effect by ANOVA, compared to control; p < 0.05. (B) On the left, whole mounts from representative adult female offspring at 18 months of age (16×). Large arrows indicate unusual, darkly staining foci; one small arrow in 5U indicates peripheral, localized increases in epithelial density observed in some PFOA-exposed animals at 18 months. On the right, histopathologic images from contralateral glands in the same animal show ductal areas that account for darkly staining foci observed on whole mounts (400×; N = 5–12 females per group). This figure was reproduced with permission from Elsevier, Inc., and is excerpted from [64].