Use of the Fischer rat thyroid follicular cell (FRTL-5) iodide uptake assay as a secondary screen of per- and polyfluoroalkyl substances (PFAS) previously identified as potential human sodium-iodide symporter (hNIS) inhibitors.
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Based on the increasing number of PFAS in the environment that have the potential to disrupt thyroid hormone function and developmental health outcomes, the U.S. EPA selected a representative set of PFAS for thyroid specific high throughput screening (HTS) targeting synthesis, transport, or clearance. One well known thyroid target of environmental chemicals is the sodium iodide symporter (NIS) that regulates iodide uptake into the thyroid gland initiating the first step of thyroid hormone synthesis. Our laboratory recently screened the ToxCast library of 149 unique PFAS substances for inhibition of NIS using a stably transduced human NIS (hNIS) cell line (hNIS-293T-EPA) in a radioactive iodide uptake (RAIU) assay. The most active PFAS chemicals identified in this hNIS screening assay included 38 of the 149 PFAS chemicals tested based on a unique ranking system based on cytotoxic interference, potency, and normalization to perchlorate response. Here, we evaluated these high ranked PFAS chemicals using a secondary FTRL-5 cell line that endogenously express the NIS, providing both a more biologically relevant screen with a cross-species comparison of NIS inhibition.