Synergistic effects of perfluoroalkyl acids mixtures with J-shaped concentration–responses on viability of a human liver cell line

Some perfluoroalkyl acids (PFAAs) are highly persistent and bioaccumulative, resulting in their broad coexisting distribution in humans and the environment. Our aim was to investigate the individual and joint effects of PFAAs on cellular viability of a human liver cell line (HL-7702) using the MTT assay. Equipartition ray design and equivalent-effect concentration ratio (EECR) mixtures were used to investigate the binary and multiple effects of PFAAs, respectively. All tested PFAAs mixtures and the individuals (except perfluorododecanoic acid (PFDoDA) and perfluorotetradecanoic acid (PFTeDA)) showed obvious non-monotonic J-shaped concentration-response curves (CRC) on HL-7702. The inhibitory effect of individual PFAAs increased with the elongation of the carbon chain and was dominated by their molecular volume. The three binary mixtures (PFOA/S, PFHxA/S and PFBA/S) showed that synergistic effects occurred under effective inhibitory concentrations (IC) of IC0, IC10, and IC50 in mixtures, while for IC-20 the synergistic effect only occurred under higher PFSA proportion in mixtures. Furthermore, EECR mixtures of the nine individual PFAAs with J-shaped CRC also showed synergistic effects. However, mixtures of the eleven individual PFAAs including those with S-shaped CRC resulted in partial addition effects on HL-7702. Our results indicated that the individual stimulatory responses of HL-7702 to PFAA may produce adverse effects in mixtures at relevant dose levels.