In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths

Perfluorooctanoic acid (PFOA) is in use for the production of fluoropolymers (PFT). Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far. In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids (PFCA) with a carbon chain length ranging from four to twelve carbon atoms. By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity. There was, however, no indication of an apoptotic mechanism for cytotoxicity. All PFCA under investigation were negative in two independent genotoxicity assays. As PFOA, being a well-known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator-activated receptor alpha (PPARα) with PFOA having the highest potential of PPARα activation. Moreover, the compounds showed weak potential to activate PPARγ and hardly activated PPARδ. Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA.

► Cytotoxicity of PFCA increases with increasing carbon chain length.
► There is a positive correlation between the PFCA carbon chain length and its potency to induce cellular proliferation.
► PFCA are not genotoxic in vitro according to the Ames test and the micronucleus assay.
► PFCA activate PPARα with PFOA being the most potent agonist.
► PFCA are weak agonists of PPARγ and PPARδ.