Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures

Contaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenon...

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Main Authors: Błażej Kudłak, Natalia Jatkowska, Wen Liu, Michael J. Williams, Damia Barcelo, Helgi B. Schiöth
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/10/3260
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author Błażej Kudłak
Natalia Jatkowska
Wen Liu
Michael J. Williams
Damia Barcelo
Helgi B. Schiöth
author_facet Błażej Kudłak
Natalia Jatkowska
Wen Liu
Michael J. Williams
Damia Barcelo
Helgi B. Schiöth
author_sort Błażej Kudłak
collection DOAJ
description Contaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenone derivatives (oxybenzone, OXYB), cinnamates (2-ethylhexyl 4-methoxycinnamate, EMC) and camphor derivatives (4-methylbenzylidene-camphor, 4MBC). Furthermore, in numerous water sources, these UV filters have been detected together with Bisphenols (BPs), which are commonly used in plastics and can be physiologically detrimental. We utilized bioluminescent bacteria (Microtox assay) to monitor these CEC mixtures at environmentally relevant doses, and performed the first systematic study involving three sunscreen components (OXYB, 4MBC and EMC) and three BPs (BPA, BPS or BPF). Moreover, a breast cell line and cell viability assay were employed to determine the possible effect of these mixtures on human cells. Toxicity modeling, with concentration addition (CA) and independent action (IA) approaches, was performed, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. The results show that UV filter sunscreen constituents and BPs interact at environmentally relevant concentrations. Of notable interest, mixtures containing any pair of three BPs (e.g., BPA + BPS, BPA + BPF and BPS + BPF), together with one sunscreen component (OXYB, 4MBC or EMC), showed strong synergy or overadditive effects. On the other hand, mixtures containing two UV filters (any pair of OXYB, 4MBC and EMC) and one BP (BPA, BPS or BPF) had a strong propensity towards concentration dependent underestimation. The three-component mixtures of UV filters (4MBC, EMC and OXYB) acted in an antagonistic manner toward each other, which was confirmed using a human cell line model. This study is one of the most comprehensive involving sunscreen constituents and BPs in complex mixtures, and provides new insights into potentially important interactions between these compounds.
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spelling doaj.art-5d6d4b925ab647b58a4d37bf1b41b22e2023-11-23T12:23:37ZengMDPI AGMolecules1420-30492022-05-012710326010.3390/molecules27103260Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component MixturesBłażej Kudłak0Natalia Jatkowska1Wen Liu2Michael J. Williams3Damia Barcelo4Helgi B. Schiöth5Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233 Gdańsk, PolandDepartment of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233 Gdańsk, PolandFunctional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, SwedenFunctional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, SwedenCatalan Institute for Water Research (ICRA), Parc Científic i Tecnològic de la Universitat de Girona, C/Emili Grahit, 101 Edifici H2O, E-17003 Girona, SpainFunctional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, SwedenContaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenone derivatives (oxybenzone, OXYB), cinnamates (2-ethylhexyl 4-methoxycinnamate, EMC) and camphor derivatives (4-methylbenzylidene-camphor, 4MBC). Furthermore, in numerous water sources, these UV filters have been detected together with Bisphenols (BPs), which are commonly used in plastics and can be physiologically detrimental. We utilized bioluminescent bacteria (Microtox assay) to monitor these CEC mixtures at environmentally relevant doses, and performed the first systematic study involving three sunscreen components (OXYB, 4MBC and EMC) and three BPs (BPA, BPS or BPF). Moreover, a breast cell line and cell viability assay were employed to determine the possible effect of these mixtures on human cells. Toxicity modeling, with concentration addition (CA) and independent action (IA) approaches, was performed, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. The results show that UV filter sunscreen constituents and BPs interact at environmentally relevant concentrations. Of notable interest, mixtures containing any pair of three BPs (e.g., BPA + BPS, BPA + BPF and BPS + BPF), together with one sunscreen component (OXYB, 4MBC or EMC), showed strong synergy or overadditive effects. On the other hand, mixtures containing two UV filters (any pair of OXYB, 4MBC and EMC) and one BP (BPA, BPS or BPF) had a strong propensity towards concentration dependent underestimation. The three-component mixtures of UV filters (4MBC, EMC and OXYB) acted in an antagonistic manner toward each other, which was confirmed using a human cell line model. This study is one of the most comprehensive involving sunscreen constituents and BPs in complex mixtures, and provides new insights into potentially important interactions between these compounds.https://www.mdpi.com/1420-3049/27/10/3260bisphenol Abisphenol A analoguessunscreenstoxicity of mixturesacute toxicityenvironmental pollution
spellingShingle Błażej Kudłak
Natalia Jatkowska
Wen Liu
Michael J. Williams
Damia Barcelo
Helgi B. Schiöth
Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
Molecules
bisphenol A
bisphenol A analogues
sunscreens
toxicity of mixtures
acute toxicity
environmental pollution
title Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
title_full Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
title_fullStr Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
title_full_unstemmed Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
title_short Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures
title_sort enhanced toxicity of bisphenols together with uv filters in water identification of synergy and antagonism in three component mixtures
topic bisphenol A
bisphenol A analogues
sunscreens
toxicity of mixtures
acute toxicity
environmental pollution
url https://www.mdpi.com/1420-3049/27/10/3260
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