Application of the transthyretin binding assay in effect-directed analysis of sediments: identification of thyroid hormone disrupting compounds

In Effect-Directed Analysis (EDA) studies, various bioassays have been implemented that have an endpoint related to endocrine disruption, with the emphasis on estrogenic and androgenic effects. To extend the scope of EDA, we have used the radioligand T4*-TTR binding assay (shortly, TTR assay) to determine the thyroid hormone like (TH-like) activity to direct our fractionation for the identification of unknown thyroid hormone disrupting environmental contaminants. From a human and animal health perspective, the thyroid function is vital for the normal development of the central nervous system of the fetus. To assess what classes of environmental toxicants are capable of interfering with the thyroid hormone system, an inventory of the different classes of compounds with reported TH-like activities was made. Compounds that are known to influence the thyroid system are, among others, hydroxylated polybrominated diphenyl ethers, hydroxylated polychlorinated biphenyls and triclosan. More recently, also polyfluorinated compounds were shown to have moderate TH-like activities. In the framework of the EU funded Modelkey project we have carried out EDA studies at several locations connected with European river systems using a variety of bioassays. Sediment extracts were fractionated using sequential reversed and normal phase liquid chromatography. In the course of this project, we identified several different classes of environmental toxicants in fractions of the responsive sediment extracts, by conventional gas chromatography coupled with mass spectrometric detection as well as liquid chromatography coupled with high resolution mass spectrometry. A selection of these compounds was tested in the TTR assay in order to assess whether they were responsible for the observed TH-like activity in the fractions of the sediment extracts.JRC.DDG.H.5-Rural, water and ecosystem resource