Differential toxicity between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)

Abstract

-Perfluoroalkyl substances (PFASs) are persistent environmental contaminants. Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are representatives of PFASs. Recently, the U.S. Environmental Protection Agency (US EPA) set the health advisory level as 70 parts per trillion for lifetime exposure to PFOS and PFOA from drinking water, based on the EPA's 2016 Health Effects Support Documents. Then, a monograph on PFOA was made available online by the International Agency for Research on Cancer, where the agency classified PFOA as "possibly carcinogenic to humans" (Group 2B). The distinction between PFOS and PFOA, however, may not be easily understood from the above documents. This paper discussed differential toxicity between PFOS and PFOA focusing on neurotoxicity, developmental toxicity and carcinogenicity, mainly based on these documents. The conclusions are as follows: Further mechanistic studies may be necessary for ultrasonic-induced PFOS-specific neurotoxicity. To support the hypothesis for PFOS-specific neonatal death that PFOS interacts directly with components of natural lung surfactant, in vivo studies to relate the physicochemical effects to lung collapse may be required. PFOA-induced DNA damage secondary to oxidative stress may develop to mutagenicity under the condition where PFOA-induced apoptosis is not sufficient to remove the damaged cells. A study to find whether PFOA induces apoptosis in normal human cells may contribute to assessment of human carcinogenicity. Studies for new targets such as hepatocyte nuclear factor 4α (HNF4α) may help clarify the underlying mechanism for PFOA-induced carcinogenicity.

Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells

“…We recently reported that PFOS promotes MCF-10A proliferation by altering important regulatory cell cycle proteins and accelerating the cell cycle (Pierozan and Karlsson 2018 ). Despite the structural and many functional similarities, PFOS and PFOA have different toxicological effects (Tsuda 2016 ). Corroborating with this, the present study revealed that PFOA induces proliferation and acceleration of cell cycle by affecting different regulatory cell cycle proteins.…”

Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in male rats

“…Nakamura et al (2016) reported that C6A as well as C8A induced DNA damage in an alkaline comet assay, using TK +/-heterozygote of the TK6 human lymphoblastoid cell line. The possibility of C8A-induced DNA damage secondary to oxidative stress by the activation of PPARα to develop into human cancer was suggested when the C8A does not induce apoptosis properly (Tsuda, 2016). Further studies of C6A in relation to human toxicity may be necessary.…”

Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells

“…Additionally, perfluorooctane sulfonate (PFOS) can promote MCF-10A breast epithelial cell proliferation by regulating cell cycle proteins and accelerating the cell cycle process (26). Although PFOS and PFOA are per-and polyfluoroalkyl substances which share structural and functional properties, they have different toxicological effects (27). The experiments performed in the present study demonstrated that PFOA promoted RD cell proliferation by regulating different cell cycle-related proteins.…”