Selected bisphenols and phthalates screened for estrogen and androgen disruption by in silico and in vitro methods

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F18%3A43917593" target="_blank" >RIV/00216208:11120/18:43917593 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/75010330:_____/18:00012508

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Selected bisphenols and phthalates screened for estrogen and androgen disruption by in silico and in vitro methods

Popis výsledku v původním jazyce

OBJECTIVES: The aim of this study was to detect endocrine disruption potential of selected bisphenols and phthalates, compare in silico prediction with results from two in vitro methods and bring up-to-date information on development of EU legislation, available in vitro methods and biomechanisms involved in endocrine disruption. MATERIAL AND METHODS: In silico approach based on the OECD QSAR Toolbox was used for prediction of estrogen receptor α binding. OECD TG 455 assay and a yeast-based YES/YAS assay was used to determine the interactions with human estrogen (ERα) and androgen receptors. RESULTS: In silico results predicted the screened phthalates as non binders and bisphenols as very strong binders of the ERα. In vitro results differed from in silico prediction in several cases but exhibited concordance mainly for strong binders of ERα. Most of the substances exhibited parallel activity (agonist-antagonist) on both estrogen and androgen receptors. Agonistic studies showed the effective concentration of 10% activity (EC10) from 5.0E-07 for strong agonists (e.g. BPC, BPTMC). Cytotoxicity was observed after 48 h exposure of S. cerevisiae to BPFL, BPG, BPM, BPTMC in concentrations starting at 3.6E-05 mol/l. CONCLUSION: Our results suggest multiple parallel interactions of tested compounds and emphasize the importance of determination of an appropriate battery of in vitro methods that will include more receptors and will be appropriate to target specific molecular mechanisms involved in endocrine disruption. Results in agonistic studies indicate agonistic potential and are supported by results of antagonistic studies with consideration of possible multiple interactions.

Název v anglickém jazyce

Selected bisphenols and phthalates screened for estrogen and androgen disruption by in silico and in vitro methods

Popis výsledku anglicky

OBJECTIVES: The aim of this study was to detect endocrine disruption potential of selected bisphenols and phthalates, compare in silico prediction with results from two in vitro methods and bring up-to-date information on development of EU legislation, available in vitro methods and biomechanisms involved in endocrine disruption. MATERIAL AND METHODS: In silico approach based on the OECD QSAR Toolbox was used for prediction of estrogen receptor α binding. OECD TG 455 assay and a yeast-based YES/YAS assay was used to determine the interactions with human estrogen (ERα) and androgen receptors. RESULTS: In silico results predicted the screened phthalates as non binders and bisphenols as very strong binders of the ERα. In vitro results differed from in silico prediction in several cases but exhibited concordance mainly for strong binders of ERα. Most of the substances exhibited parallel activity (agonist-antagonist) on both estrogen and androgen receptors. Agonistic studies showed the effective concentration of 10% activity (EC10) from 5.0E-07 for strong agonists (e.g. BPC, BPTMC). Cytotoxicity was observed after 48 h exposure of S. cerevisiae to BPFL, BPG, BPM, BPTMC in concentrations starting at 3.6E-05 mol/l. CONCLUSION: Our results suggest multiple parallel interactions of tested compounds and emphasize the importance of determination of an appropriate battery of in vitro methods that will include more receptors and will be appropriate to target specific molecular mechanisms involved in endocrine disruption. Results in agonistic studies indicate agonistic potential and are supported by results of antagonistic studies with consideration of possible multiple interactions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/EF16_019%2F000860" target="_blank" >EF16_019/000860: Mezinárodní konkurenceschopnost SZÚ ve výzkumu, vývoji a vzdělávání v alternativních toxikologických metodách.</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Neuroendocrinology Letters

ISSN

0172-780X

e-ISSN

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Svazek periodika

39

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

SE - Švédské království

Počet stran výsledku

8

Strana od-do

409-416

Kód UT WoS článku

000457550600009

EID výsledku v databázi Scopus

2-s2.0-85062587305