20.500.12556/RUL-141905 Triclocarban, triclosan, bromochlorophene, chlorophene, and climbazole effects on nuclear receptors an in silico and in vitro study 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. luciferase inhibition effects of preservatives triclocarban preservatives toksičnost kozmetičnih izdelkov toksikološki testi kozmetični izdelki toksičnost androgeni true false true Angleški jezik Slovenski jezik 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) Članek v reviji 2022-10-11 10:40:45 2022-10-11 10:40:48 2025-05-16 14:59:44 0000-00-00 00:00:00 2020 0 0 17 str. iss. 10, art. 107005 Vol. 128 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.9:665.58 1552-9924 10.1289/EHP6596 33050371 kenda-et-al-2020-triclocarban-triclosan-bromochlorophene-chlorophene-and-climbazole-effects-on-nuclear-receptors-an-in.pdf kenda-et-al-2020-triclocarban-triclosan-bromochlorophene-chlorophene-and-climbazole-effects-on-nuclear-receptors-an-in.pdf 1 76E487DDDDB1C24EBCAC7AD07B0B6B7A 72bcf08b2c1db7999d676bb0f532060a9321eaeabfd4f7ab75d24fc381bf86c7 56e0dd6c-151d-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=201586 https://ehp.niehs.nih.gov/doi/10.1289/EHP6596 1 602d41c7-4940-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=163075 Fakulteta za farmacijo 0 0 0