Endocrine Disruptor Potential of Short- and Long-Chain Perfluoroalkyl Substances (PFASs)-A Synthesis of Current Knowledge with Proposal of Molecular Mechanism

Abstract

Endocrine disruptors are a group of chemical compounds that, even in low concentrations, cause a hormonal imbalance in the body, contributing to the development of various harmful health disorders. Many industry compounds, due to their important commercial value and numerous applications, are produced on a global scale, while the mechanism of their endocrine action has not been fully understood. In recent years, per- and polyfluoroalkyl substances (PFASs) have gained the interest of major international health organizations, and thus more and more studies have been aimed to explain the toxicity of these compounds. PFASs were firstly synthesized in the 1950s and broadly used in the industry in the production of firefighting agents, cosmetics and herbicides. The numerous industrial applications of PFASs, combined with the exceptionally long half-life of these substances in the human body and extreme environmental persistence, result in a common and chronic exposure of the general population to their action. Available data have suggested that human exposure to PFASs can occur during different stages of development and may cause short- or/and long-term health effects. This paper synthetizes the current literature reports on the presence, bioaccumulation and, particularly, endocrine toxicity of selected long- and short-chain PFASs, with a special emphasis on the mechanisms underlying their endocrine actions.

Keywords: PFHxS; PFOA; PFOS; endocrine disruptor; perfluoroalkyl substances; prenatal exposure; short-chain PFASs.

Figure 1

Chemical structures of perfluorooctanoic acid (PFOA) (A) and perfluorooctane sulfonic acid (PFOS) (B).

Figure 2

Alterations in hypothalamic–pituitary–gonadal axis functions with potential health effects caused by per- and polyfluoroalkyl substances (PFASs) exposure [32,44,46,151,152,153,154].

Figure 3

Potential molecular mechanism of PFASs hepatotoxicity. In liver cells, PFASs activate peroxisome-proliferator-activated receptor (PPAR), which induces heterodimerization with retinoid x receptor (RXR). Complex binds to specific sequence of DNA–PPREs (peroxisome-proliferator hormone-response elements), which occurs in the promoter region of a gene and modulate transcription. Based on papers of Reference [170].

Figure 4

Transcriptional regulators of the cholesterol transformations via ER in male and female–implications caused by PFASs. ER, endocrine (nuclear) receptor.

Figure 5

Concentrations of PFOS (mean) in maternal, cord and children serum [136,193]. The blood–placenta barrier limits the penetration of PFASs to the fetus. In the first years of life, the concentration of PFASs in the serum starts to increase.