Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F17%3A00095509" target="_blank" >RIV/00216224:14310/17:00095509 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0048969717305478?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0048969717305478?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.scitotenv.2017.03.043" target="_blank" >10.1016/j.scitotenv.2017.03.043</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells

Popis výsledku v původním jazyce

2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on transEHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25 mu g mL(-1). trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25 mu g mL(-1). The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and transEHMC was detected at the concentration 25 pg mL-1. The No observed adverse effect level (NOAEL, mg kg lbw day I) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL(trans-EHMC) = 3.07, NOAEL(cis-EHMC) = 0.30 for TK-6 and NOAEL(trans-EHMC) = 26.46, NOAEL(cis-EHMC) = 20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RID, mg kg(-1) bw day(-1)) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HIcis-EHMC was 7 times higher than HItrans-EHMC In terms of CDI, relative contributions were; dermal exposure route &gt; oral &gt; inhalation. According to our results we recommend the RfD(trans-EHMC) = 0.20 and RfD(cis-EHMC) = 0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs.

Název v anglickém jazyce

Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells

Popis výsledku anglicky

2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on transEHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25 mu g mL(-1). trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25 mu g mL(-1). The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and transEHMC was detected at the concentration 25 pg mL-1. The No observed adverse effect level (NOAEL, mg kg lbw day I) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL(trans-EHMC) = 3.07, NOAEL(cis-EHMC) = 0.30 for TK-6 and NOAEL(trans-EHMC) = 26.46, NOAEL(cis-EHMC) = 20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RID, mg kg(-1) bw day(-1)) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HIcis-EHMC was 7 times higher than HItrans-EHMC In terms of CDI, relative contributions were; dermal exposure route &gt; oral &gt; inhalation. According to our results we recommend the RfD(trans-EHMC) = 0.20 and RfD(cis-EHMC) = 0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10511 - Environmental sciences (social aspects to be 5.7)

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)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Science of the Total Environment

ISSN

0048-9697

e-ISSN

—

Svazek periodika

593

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

18-26

Kód UT WoS článku

000401201800003

EID výsledku v databázi Scopus

—