Triclocarban, triclosan, bromochlorophene, chlorophene, and climbazole effects on nuclear receptors : an in silico and in vitro study

Kenda, Maša (avtor), Karas Kuželički, Nataša (avtor), Iida, Mitsuru (avtor), Kojima, Hiroyuki (avtor), Sollner Dolenc, Marija (avtor)

BACKGROUND: Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because in vivo testing is now banned completely in the European Union. OBJECTIVES: The aim was to identify candidate preservatives as endocrine disruptors by in silico methods and to confirm endocrine receptors’ activities through nuclear receptors in vitro. METHODS: We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 in silico tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (ERα), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in vitro in AR-EcoScreen, hERα-HeLa-9903, MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition). RESULTS: Triclocarban had agonist activity on AR and ERα at 1 μM and antagonist activity on GR at 5 μM and TR at 1 μM. Triclosan showed antagonist effects on AR, ERα, GR at 10 μM and TR at 5 μM, and bromochlorophene at 1 μM (AR and TR) and at 10 μM (ERα and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC$_{50}$) IC$_{50}$ = 2.4 μM], as for its substantial ERα agonist at > 5 μM and TR antagonist activity at 10 μM. Climbazole showed AR antagonist (IC$_{50}$ = 13.6 μM), ERα agonist at > 10 μM, and TR antagonist activity at 10 μM. DISCUSSION: These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment.

• Jezik: Angleški jezik
• Ključne besede: luciferase inhibition, effects of preservatives triclocarban, preservatives
• 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: 2020
• Št. strani: 17 str.
• Številčenje: Vol. 128, iss. 10, art. 107005
• PID: 20.500.12556/RUL-141905
• UDK: 615.9:665.58
• ISSN pri članku: 1552-9924
• DOI: 10.1289/EHP6596
• COBISS.SI-ID: 33050371

Avtorske pravice

Revija Environmental health perspectives izhaja v odprtem dostopu (glej rubriko »Information and Authors« na zgoraj navedenem izvornem URL-ju) in zanjo velja licenca Creative Commons (glej zapis za revijo v DOAJ https://doaj.org/toc/0091-6765). (Datum opombe: 16. 5. 2025)

• Datum objave v RUL: 11.10.2022

Gradivo je del revije

• Naslov: Environmental health perspectives
• Skrajšan naslov: Environ. health perspect.
• Založnik: EHP Publishing, National Institute of Environmental Health Sciences
• ISSN: 1552-9924
• COBISS.SI-ID: 520597017

Licence

• Licenca: CC0 1.0, Creative Commons CC0 1.0 Univerzalna
• Povezava: https://creativecommons.org/publicdomain/zero/1.0/deed.sl
• Opis: CC Zero omogoča znanstvenikom, izobraževalcem, umetnikom in drugim ustvarjalcem ter lastnikom vsebin, zavarovanih z avtorsko pravico ali zbirko podatkov, da se odpovejo pravicam na svojih delih in jih tako čim bolj celovito predajo v javno domeno, da bodo drugi lahko prosto gradili, izboljševali in ponovno uporabljali dela za kakršne koli namene brez omejitev v skladu z zakonodajo o avtorskih pravicah ali zbirkah podatkov.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: toksičnost kozmetičnih izdelkov, toksikološki testi, kozmetični izdelki, toksičnost, androgeni

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Program financ.: Young researchers

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin