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

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

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.

• Language: English
• Keywords: luciferase inhibition, effects of preservatives triclocarban, preservatives
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 17 str.
• Numbering: Vol. 128, iss. 10, art. 107005
• PID: 20.500.12556/RUL-141905
• UDC: 615.9:665.58
• ISSN on article: 1552-9924
• DOI: 10.1289/EHP6596
• COBISS.SI-ID: 33050371

Copyright

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)

• Publication date in RUL: 11.10.2022

Record is a part of a journal

• Title: Environmental health perspectives
• Shortened title: Environ. health perspect.
• Publisher: EHP Publishing, National Institute of Environmental Health Sciences
• ISSN: 1552-9924
• COBISS.SI-ID: 520597017

Licences

• License: CC0 1.0, Creative Commons CC0 1.0 Universal
• Link: https://creativecommons.org/publicdomain/zero/1.0/deed.en
• Description: CC Zero enables scientists, educators, artists and other creators and owners of copyright- or database-protected content to waive those interests in their works and thereby place them as completely as possible in the public domain, so that others may freely build upon, enhance and reuse the works for any purposes without restriction under copyright or database law.

Secondary language

• Language: Slovenian
• Keywords: toksičnost kozmetičnih izdelkov, toksikološki testi, kozmetični izdelki, toksičnost, androgeni

Projects

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Young researchers

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