Dataset Information

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study.

ABSTRACT:

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 1μM and antagonist activity on GR at 5μM and TR at 1μM. Triclosan showed antagonist effects on AR, ERα, GR at 10μM and TR at 5μM, and bromochlorophene at 1μM (AR and TR) and at 10μM (ERα and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC₅₀) IC50=2.4μM], as for its substantial ERα agonist at >5μM and TR antagonist activity at 10μM. Climbazole showed AR antagonist (IC50=13.6μM), ERα agonist at >10μM, and TR antagonist activity at 10μM.

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. https://doi.org/10.1289/EHP6596.

SUBMITTER: Kenda M

PROVIDER: S-EPMC7567334 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An <i>in Silico</i> and <i>in Vitro</i> Study.

Kenda Maša M Karas Kuželički Nataša N Iida Mitsuru M Kojima Hiroyuki H Sollner Dolenc Marija M

Environmental health perspectives 20201016 10

<h4>Background</h4>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 <i>in vivo</i> testing is now banned completely in the European Union.<h4>Objectives</h4>The aim was to identify candidate preservatives as endocrine disruptors by <i>in silico</ ...[more]

PMID: 33064576

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