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Triclocarban, triclosan, bromochlorophene, chlorophene, and climbazole effects on nuclear receptors : an in silico and in vitro study
ID
Kenda, Maša
(
Avtor
),
ID
Karas Kuželički, Nataša
(
Avtor
),
ID
Iida, Mitsuru
(
Avtor
),
ID
Kojima, Hiroyuki
(
Avtor
),
ID
Sollner Dolenc, Marija
(
Avtor
)
URL - Izvorni URL, za dostop obiščite
https://ehp.niehs.nih.gov/doi/10.1289/EHP6596
Galerija slik
Izvleček
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.
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:
Str. 107005-1 - 077002-17
Številčenje:
Vol. 128, no. 10
PID:
20.500.12556/RUL-141905
UDK:
615.9:665.58
ISSN pri članku:
1552-9924
DOI:
10.1289/EHP6596
COBISS.SI-ID:
33050371
Datum objave v RUL:
11.10.2022
Število ogledov:
421
Število prenosov:
21
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Objavi na:
Gradivo je del revije
Naslov:
Environmental health perspectives
Skrajšan naslov:
Environ. health perspect.
Založnik:
National Institute of Environmental Health Sciences, National Institutes of Health, Dept. of Health, Education and Welfare
ISSN:
1552-9924
COBISS.SI-ID:
520597017
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
toksičnost kozmetičnih izdelkov
,
toksikološki testi
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P1-0208-2015
Naslov:
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Young Researchers Programme
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