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

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

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.

• Jezik: Angleški jezik
• Ključne besede: PFAS, endocrine disruptome, VirtualToxLab, endocrine disruption, androgen receptor, estrogen receptor, glucocorticoid receptor, in silico, new approach methods, hormonski motilci, imunomodulacija
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 21 str.
• Številčenje: Vol. 15, iss. 5, [article no.] 136
• PID: 20.500.12556/RUL-171388
• UDK: 616.4
• ISSN pri članku: 2039-4713
• DOI: 10.3390/jox15050136
• COBISS.SI-ID: 246382595
• Datum objave v RUL: 25.08.2025

Gradivo je del revije

• Naslov: Journal of xenobiotics
• Skrajšan naslov: J. xenobiotics
• Založnik: PagePress Publications
• ISSN: 2039-4713
• COBISS.SI-ID: 520181017

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: PFAS, endokrine motnje, VirtualToxLab, endokrine motnje, androgeni receptor, estrogenski receptor, glukokortikoidni receptor, in silico, nove metode pristopa

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin