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Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles
A growing body of experimental evidence indicates that the in vitro effects of mixtures of estrogenic chemicals can be well predicted from the estrogenicity of their components by the concentration addition (CA) concept. However, some studies have observed small deviations from CA. Factors affecting...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422259/ https://www.ncbi.nlm.nih.gov/pubmed/22912892 http://dx.doi.org/10.1371/journal.pone.0043606 |
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author | Evans, Richard Mark Scholze, Martin Kortenkamp, Andreas |
author_facet | Evans, Richard Mark Scholze, Martin Kortenkamp, Andreas |
author_sort | Evans, Richard Mark |
collection | PubMed |
description | A growing body of experimental evidence indicates that the in vitro effects of mixtures of estrogenic chemicals can be well predicted from the estrogenicity of their components by the concentration addition (CA) concept. However, some studies have observed small deviations from CA. Factors affecting the presence or observation of deviations could include: the type of chemical tested; number of mixture components; mixture design; and assay choice. We designed mixture experiments that address these factors, using mixtures with high numbers of components, chemicals from diverse chemical groups, assays with different in vitro endpoints and different mixture designs and ratios. Firstly, the effects of mixtures composed of up to 17 estrogenic chemicals were examined using estrogenicity assays with reporter-gene (ERLUX) and cell proliferation (ESCREEN) endpoints. Two mixture designs were used: 1) a ‘balanced’ design with components present in proportion to a common effect concentration (e.g. an EC(10)) and 2) a ‘non-balanced’ design with components in proportion to potential human tissue concentrations. Secondly, the individual and simultaneous ability of 16 potential modulator chemicals (each with minimal estrogenicity) to influence the assay outcome produced by a reference mixture of estrogenic chemicals was examined. Test chemicals included plasticizers, phthalates, metals, PCBs, phytoestrogens, PAHs, heterocyclic amines, antioxidants, UV filters, musks, PBDEs and parabens. In all the scenarios tested, the CA concept provided a good prediction of mixture effects. Modulation studies revealed that chemicals possessing minimal estrogenicity themselves could reduce (negatively modulate) the effect of a mixture of estrogenic chemicals. Whether the type of modulation we observed occurs in practice most likely depends on the chemical concentrations involved, and better information is required on likely human tissue concentrations of estrogens and of potential modulators. Successful prediction of the effects of diverse chemical combinations might be more likely if chemical profiling included consideration of effect modulation. |
format | Online Article Text |
id | pubmed-3422259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34222592012-08-21 Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles Evans, Richard Mark Scholze, Martin Kortenkamp, Andreas PLoS One Research Article A growing body of experimental evidence indicates that the in vitro effects of mixtures of estrogenic chemicals can be well predicted from the estrogenicity of their components by the concentration addition (CA) concept. However, some studies have observed small deviations from CA. Factors affecting the presence or observation of deviations could include: the type of chemical tested; number of mixture components; mixture design; and assay choice. We designed mixture experiments that address these factors, using mixtures with high numbers of components, chemicals from diverse chemical groups, assays with different in vitro endpoints and different mixture designs and ratios. Firstly, the effects of mixtures composed of up to 17 estrogenic chemicals were examined using estrogenicity assays with reporter-gene (ERLUX) and cell proliferation (ESCREEN) endpoints. Two mixture designs were used: 1) a ‘balanced’ design with components present in proportion to a common effect concentration (e.g. an EC(10)) and 2) a ‘non-balanced’ design with components in proportion to potential human tissue concentrations. Secondly, the individual and simultaneous ability of 16 potential modulator chemicals (each with minimal estrogenicity) to influence the assay outcome produced by a reference mixture of estrogenic chemicals was examined. Test chemicals included plasticizers, phthalates, metals, PCBs, phytoestrogens, PAHs, heterocyclic amines, antioxidants, UV filters, musks, PBDEs and parabens. In all the scenarios tested, the CA concept provided a good prediction of mixture effects. Modulation studies revealed that chemicals possessing minimal estrogenicity themselves could reduce (negatively modulate) the effect of a mixture of estrogenic chemicals. Whether the type of modulation we observed occurs in practice most likely depends on the chemical concentrations involved, and better information is required on likely human tissue concentrations of estrogens and of potential modulators. Successful prediction of the effects of diverse chemical combinations might be more likely if chemical profiling included consideration of effect modulation. Public Library of Science 2012-08-17 /pmc/articles/PMC3422259/ /pubmed/22912892 http://dx.doi.org/10.1371/journal.pone.0043606 Text en © 2012 Evans et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Evans, Richard Mark Scholze, Martin Kortenkamp, Andreas Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title | Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title_full | Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title_fullStr | Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title_full_unstemmed | Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title_short | Additive Mixture Effects of Estrogenic Chemicals in Human Cell-Based Assays Can Be Influenced by Inclusion of Chemicals with Differing Effect Profiles |
title_sort | additive mixture effects of estrogenic chemicals in human cell-based assays can be influenced by inclusion of chemicals with differing effect profiles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422259/ https://www.ncbi.nlm.nih.gov/pubmed/22912892 http://dx.doi.org/10.1371/journal.pone.0043606 |
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