title: Effect-directed analysis to explore the polar bear exposome: identification of thyroid hormone disrupting compounds in plasma.
abstract: Compounds with transthyretin (TTR)-binding potency in the blood plasma of polar bear cubs were identified with effect-directed analysis (EDA). This approach contributes to the understanding of the thyroid disrupting exposome of polar bears. The selection of these samples for in-depth EDA was based on the difference between the observed TTR-binding potency on the one hand and the calculated potency (based on known concentrations of TTR-binding compounds and their relative potencies) on the other. A library-based identification was applied to the liquid chromatography-time-of-flight-mass spectrometry (LC-ToF-MS) data by screening for matches between compound lists and the LC-ToF-MS data regarding accurate mass and isotope pattern. Then, isotope cluster analysis (ICA) was applied to the LC-ToF-MS data allowing specific screening for halogen isotope patterns. The presence of linear and branched nonylphenol (NP) was observed for the first time in polar bears. Furthermore, the presence of one di- and two monohydroxylated octachlorinated biphenyls (octaCBs) was revealed in the extracts. Linear and branched NP, 4'-OH-CB201 and 4,4'-OH-CB202 could be successfully confirmed with respect to their retention time in the analytical system. In addition, branched NP, mono- and dihydroxylated-octaCBs showed TTR-binding potencies and could explain another 32 ± 2% of the total measured activities in the extracts.
authors.affiliation: Institute for Environmental Studies (IVM), VU University Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
authors.forename: Eszter
authors.initials: E
authors.lastname: Simon
authors.forename: Martin
authors.initials: M
authors.lastname: van Velzen
authors.forename: Sicco H
authors.initials: SH
authors.lastname: Brandsma
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lie
authors.forename: Katharina
authors.initials: K
authors.lastname: Løken
authors.forename: Jacob
authors.initials: J
authors.lastname: de Boer
authors.forename: Jenny
authors.initials: J
authors.lastname: Bytingsvik
authors.forename: Bjørn M
authors.initials: BM
authors.lastname: Jenssen
authors.forename: Jon
authors.initials: J
authors.lastname: Aars
authors.forename: Timo
authors.initials: T
authors.lastname: Hamers
authors.forename: Marja H
authors.initials: MH
authors.lastname: Lamoree
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D052244:Endocrine Disruptors / Q000097:blood* / Q000633:toxicity; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood* / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D013058:Mass Spectrometry; D013963:Thyroid Hormones / Q000097:blood*; D001503:Ursidae
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D013963:Thyroid Hormones