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Triclocarban, triclosan, bromochlorophene, chlorophene, and climbazole effects on nuclear receptors : an in silico and in vitro study
ID
Kenda, Maša
(
Author
),
ID
Karas Kuželički, Nataša
(
Author
),
ID
Iida, Mitsuru
(
Author
),
ID
Kojima, Hiroyuki
(
Author
),
ID
Sollner Dolenc, Marija
(
Author
)
URL - Source URL, Visit
https://ehp.niehs.nih.gov/doi/10.1289/EHP6596
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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 (ER[alpha]), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in vitro in AR-EcoScreen, hER[alpha]-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 ER[alpha] at 1[micro]M and antagonist activity on GR at 5[micro]M and TR at 1[micro]M. Triclosan showed antagonist effects on AR, ER[alpha], GR at 10[micro]M and TR at 5[micro]M, and bromochlorophene at 1[micro]M (AR and TR) and at 10[micro]M (ER[alpha] and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC50) IC50=2.4[micro]M], as for its substantial ER[alpha] agonist at >5[micro]M and TR antagonist activity at 10[micro]M. Climbazole showed AR antagonist (IC50=13.6[micro]M), ER[alpha] agonist at >10[micro]M, and TR antagonist activity at 10[micro]M.
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:
Str. 107005-1 - 077002-17
Numbering:
Vol. 128, no. 10
PID:
20.500.12556/RUL-141905
UDC:
615.9:665.58
ISSN on article:
1552-9924
DOI:
10.1289/EHP6596
COBISS.SI-ID:
33050371
Publication date in RUL:
11.10.2022
Views:
422
Downloads:
21
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Record is a part of a journal
Title:
Environmental health perspectives
Shortened title:
Environ. health perspect.
Publisher:
National Institute of Environmental Health Sciences, National Institutes of Health, Dept. of Health, Education and Welfare
ISSN:
1552-9924
COBISS.SI-ID:
520597017
Secondary language
Language:
Slovenian
Keywords:
toksičnost kozmetičnih izdelkov
,
toksikološki testi
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P1-0208-2015
Name:
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin
Funder:
Other - Other funder or multiple funders
Funding programme:
Young Researchers Programme
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