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Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals
Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Institute of Environmental Health Sciences
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546348/ https://www.ncbi.nlm.nih.gov/pubmed/23052129 http://dx.doi.org/10.1289/ehp.1205065 |
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author | Rotroff, Daniel M. Dix, David J. Houck, Keith A. Knudsen, Thomas B. Martin, Matthew T. McLaurin, Keith W. Reif, David M. Crofton, Kevin M. Singh, Amar V. Xia, Menghang Huang, Ruili Judson, Richard S. |
author_facet | Rotroff, Daniel M. Dix, David J. Houck, Keith A. Knudsen, Thomas B. Martin, Matthew T. McLaurin, Keith W. Reif, David M. Crofton, Kevin M. Singh, Amar V. Xia, Menghang Huang, Ruili Judson, Richard S. |
author_sort | Rotroff, Daniel M. |
collection | PubMed |
description | Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S). Objective: In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays. Method: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance. Results: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data. Conclusions: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays. |
format | Online Article Text |
id | pubmed-3546348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-35463482013-02-12 Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals Rotroff, Daniel M. Dix, David J. Houck, Keith A. Knudsen, Thomas B. Martin, Matthew T. McLaurin, Keith W. Reif, David M. Crofton, Kevin M. Singh, Amar V. Xia, Menghang Huang, Ruili Judson, Richard S. Environ Health Perspect Review Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S). Objective: In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays. Method: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance. Results: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data. Conclusions: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays. National Institute of Environmental Health Sciences 2012-09-28 2013-01 /pmc/articles/PMC3546348/ /pubmed/23052129 http://dx.doi.org/10.1289/ehp.1205065 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Review Rotroff, Daniel M. Dix, David J. Houck, Keith A. Knudsen, Thomas B. Martin, Matthew T. McLaurin, Keith W. Reif, David M. Crofton, Kevin M. Singh, Amar V. Xia, Menghang Huang, Ruili Judson, Richard S. Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title | Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title_full | Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title_fullStr | Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title_full_unstemmed | Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title_short | Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals |
title_sort | using in vitro high throughput screening assays to identify potential endocrine-disrupting chemicals |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546348/ https://www.ncbi.nlm.nih.gov/pubmed/23052129 http://dx.doi.org/10.1289/ehp.1205065 |
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