Developing potency factors for thyroid hormone disruption by PFASs using TTR-TRβ CALUX® bioassay and assessment of PFASs mixtures in technical products

•All PFASs here tested affected the T4 binding to TTR, an important plasma thyroid hormone transport protein.•In vitro toxicity potency factors were established for thyroid hormone disruption potential using the novel TTR-TRβ CALUX® bioassay for major PFASs.•Similar effect-based trigger values by applying in vitro and in vivo potency factors were observed for water (3.0 vs. 2.9 to 4.6 μg PFOA-EQ/L).•AFFF surfactants and CMS (with and without TOP assay) did show similar PFOA-EQ levels by chemical and biological analysis. Over the last decade, per- and polyfluoroalkyl substances (PFASs) have become one of the most heavily investigated persistent organohalogen compound class of environmental concern. However, knowledge about their toxicology is still scarce, although PFASs as individual compounds and their industrial mixtures were shown to exert effects on the thyroid hormone system. In vitro toxicity potency factors were established for thyroid hormone transport disruption potential using the novel TTR-TRβ CALUX® bioassay for major PFASs. We assessed technical PFASs mixtures, including aqueous film-forming foam (AFFF) surfactants and chromium mist suppressants (CMS) applications with and without total oxidizable precursor (TOP) by TTR-TRβ CALUX® assay for their thyroid hormone transport disrupting potential. All PFASs listed in the German guideline for drinking water (German Environment Agency, 2017) affected the T4 binding to TTR, an important plasma thyroid hormone transport protein. For all tested PFASs, potency factors based on PC80 values relative to PFOA could be obtained and ranged between PFBA (0.0018) and PFOS (2.0). Applying in vitro potency factors obtained from the present in vitro TTR-TRβ CALUX® assay study and recently reported in vivo potency factors (Zeilmaker et al., 2018; Bil et al., 2021) on the above-mentioned German guideline for PFAS in drinking water, showed that the cumulative effect-based trigger values (in vivo and in vitro) are comparable (3.0 vs. 2.9 to 4.6 μg PFOA-EQ/l). Additionally, AFFF surfactants and CMS with and without TOP assay were tested. Highest activities were found in the older AFFF surfactants (2013/2014) due to higher PFOS/PFOA levels, which were already substituted with 6:2 FTS in 2019, resulting in much lower PFOA-EQ levels. As expected also the PFOA-EQ levels increased in the samples with TOP treatment compared to the original AFFF surfactants and CMS as confirmed here by biological and chemical PFOA-equivalents