Anti-androgenic activity of novel flame retardants in mixtures: Newly identified contribution from tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F23%3A00134410" target="_blank" >RIV/00216224:14310/23:00134410 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045653523022737" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045653523022737</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chemosphere.2023.140004" target="_blank" >10.1016/j.chemosphere.2023.140004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Anti-androgenic activity of novel flame retardants in mixtures: Newly identified contribution from tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO)

Popis výsledku v původním jazyce

In recent decades, male infertility has been on the rise, largely attributed to exposure to chemicals with endocrine-disrupting properties. The adverse effects of disrupting androgen actions on the development and reproductive health of children and adolescents have been extensively studied. Flame retardants (FRs), used in consumer products to delay flammability, have been identified as antagonists of the androgen receptor (AR), potentially leading to adverse outcomes in male reproductive health later in life. This study examined the interaction of eight novel FRs with the AR, employing an in vitro AR-dependent luciferase reporter gene assay utilizing MDA-kb2 cells. The investigation revealed the anti-androgenic activity of tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), a frequently detected FR in the environment. Furthermore, TDBP-TAZTO contributed to anti-androgenic activity when combined with six other anti-androgenic FRs. The mixture effects were predicted by three commonly employed models: concentration addition (CA), generalized CA, and independent action, with the CA model showcasing the highest accuracy. This suggests that all FRs act through a similar mechanism, as further confirmed by in silico molecular docking, indicating limited synergy or antagonism. Importantly, in the mixtures, each FR contributed to the induction of anti-androgenic effects at concentrations below their individual effective concentrations in single exposures. This raises concern for public health, especially considering the co-detection of these FRs and their potential co-occurrence with other anti-androgenic chemicals like bisphenols. Therefore, our findings, along with previous research, strongly support the incorporation of combined effects of mixtures in risk assessment to efficiently safeguard population health.

Název v anglickém jazyce

Anti-androgenic activity of novel flame retardants in mixtures: Newly identified contribution from tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO)

Popis výsledku anglicky

In recent decades, male infertility has been on the rise, largely attributed to exposure to chemicals with endocrine-disrupting properties. The adverse effects of disrupting androgen actions on the development and reproductive health of children and adolescents have been extensively studied. Flame retardants (FRs), used in consumer products to delay flammability, have been identified as antagonists of the androgen receptor (AR), potentially leading to adverse outcomes in male reproductive health later in life. This study examined the interaction of eight novel FRs with the AR, employing an in vitro AR-dependent luciferase reporter gene assay utilizing MDA-kb2 cells. The investigation revealed the anti-androgenic activity of tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), a frequently detected FR in the environment. Furthermore, TDBP-TAZTO contributed to anti-androgenic activity when combined with six other anti-androgenic FRs. The mixture effects were predicted by three commonly employed models: concentration addition (CA), generalized CA, and independent action, with the CA model showcasing the highest accuracy. This suggests that all FRs act through a similar mechanism, as further confirmed by in silico molecular docking, indicating limited synergy or antagonism. Importantly, in the mixtures, each FR contributed to the induction of anti-androgenic effects at concentrations below their individual effective concentrations in single exposures. This raises concern for public health, especially considering the co-detection of these FRs and their potential co-occurrence with other anti-androgenic chemicals like bisphenols. Therefore, our findings, along with previous research, strongly support the incorporation of combined effects of mixtures in risk assessment to efficiently safeguard population health.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemosphere

ISSN

0045-6535

e-ISSN

1879-1298

Svazek periodika

341

Číslo periodika v rámci svazku

November 2023

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1-11

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85170091323