Evaluation of endocrine disruptome and virtualToxLab for predicting per- and polyfluoroalkyl substances binding to nuclear receptors

Franko, Nina (author), Vetrih, Manca (author), Sollner Dolenc, Marija (author)

This study investigated whether the Endocrine Disruptome and VirtualToxLab in silico platforms are suitable for predicting the endocrine disrupting effects of per- and polyfluoroalkyl substances (PFASs)—in particular, for interactions with oestrogen receptors (ERs) and androgen receptor (AR). Compounds included in the U.S. Environmental Protection Agency’s PFAS working list were analysed with both models, and the results were compared with the available in vitro data regarding their modulation of nuclear receptors. Based on the identified prediction parameters, such as sensitivity, specificity, accuracy, and Mathews’ correlation coefficient, VirtualToxLab was found to be a reliable model for predicting the reactivity of PFASs with AR, while a positive consensus approach of both platforms provided reliable predictions of the PFAS reactivity with ERα and ERβ. This study provides the evidence that Endocrine Disruptome and VirtualToxLab can be used as a tier 1 screening tool for assessment of the endocrine disrupting effect of PFASs. Furthermore, it demonstrates that the likelihood of endocrine disrupting properties increases with the lipophilicity of PFASs and identifies the understudied PFHpS, PFNS, PFDS, 9-Cl, NMeFOSAA, NEtFOSAA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 6:2 monoPAP, 8:2 monoPAP, and 5:3 acid as potential ligands of AR and/or ERs.

• Language: English
• Keywords: PFAS, endocrine disruptome, VirtualToxLab, endocrine disruption, androgen receptor, estrogen receptor, glucocorticoid receptor, in silico, new approach methods, hormonski motilci, imunomodulacija
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 21 str.
• Numbering: Vol. 15, iss. 5, [article no.] 136
• PID: 20.500.12556/RUL-171388
• UDC: 616.4
• ISSN on article: 2039-4713
• DOI: 10.3390/jox15050136
• COBISS.SI-ID: 246382595
• Publication date in RUL: 25.08.2025

Record is a part of a journal

• Title: Journal of xenobiotics
• Shortened title: J. xenobiotics
• Publisher: PagePress Publications
• ISSN: 2039-4713
• COBISS.SI-ID: 520181017

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: PFAS, endokrine motnje, VirtualToxLab, endokrine motnje, androgeni receptor, estrogenski receptor, glukokortikoidni receptor, in silico, nove metode pristopa

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin