Identification of Hydrocarbon Sulfonates as Previously Overlooked Transthyretin Ligands in the Environment

Abstract

Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (∼1%) of in vitro human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein A ffinity P urification with N ontargeted A nalysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T4 displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants (e.g., dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4′-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC50 of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92–17.0 and 5.74–54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.