Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.chemosphere.2023.140611
Licence creative commons licence
Title (Primary) In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors
Author Kühne, R. ORCID logo ; Hilscherová, K.; Smutna, M.; Leßmöllmann, F.; Schüürmann, G.
Source Titel Chemosphere
Year 2024
Department EXPO
Volume 348
Page From art. 140611
Language englisch
Topic T9 Healthy Planet
Keywords In silico assessment; Thyroid hormone disruptors; Retinoid; Bioavailability; Absorption; Penetration; Permeation; Blood/brain partitioning
UFZ wide themes ERGO
Abstract Among endocrine disruption, interference with the thyroid hormone (TH) regulation is of increasing concern. Respective compounds encode through their structural features both the potential for TH disruption, and the bioavailability mitigating the toxicological effect. The aim of this study is to provide a substructure-based screening-level QSAR (quantitative structure-activity relationship) that discriminates bioavailable TH disruptors from not bioavailable counterparts, covering both direct and indirect (retinoid- and AhR-mediated) modes of action. The QSAR has been derived from literature data for 1642 compounds, and takes into account Lipinski's rule-of-five and the brain/blood partition coefficient Kbrain/blood. For its validation, an external test set of 145 substances has been used. For 1787 compounds meeting the model application domain, the model yields only one false negative. The discussion addresses the mechanistic meaning of the bioavailability triggers molecular weight, H-bond donor and acceptor, hydrophobicity (log Kow), and the physicochemical properties underlying log Kbrain/blood. The model may serve as bioavailability-screening step within a decision support system for the predictive assessment of chemicals regarding their potential to disrupt thyroid hormone function in a direct or indirect manner.
Persistent UFZ Identifier
Kühne, R., Hilscherová, K., Smutna, M., Leßmöllmann, F., Schüürmann, G. (2024):
In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors
Chemosphere 348 , art. 140611 10.1016/j.chemosphere.2023.140611