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Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays
In next generation risk assessment (NGRA), the Dietary Comparator Ratio (DCR) can be used to assess the safety of chemical exposures to humans in a 3R compliant approach. The DCR compares the Exposure Activity Ratio (EAR) for exposure to a compound of interest (EAR(test)) to the EAR for an establish...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182946/ https://www.ncbi.nlm.nih.gov/pubmed/37087486 http://dx.doi.org/10.1007/s00204-023-03480-w |
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author | van Tongeren, Tessa C. A. Wang, Si Carmichael, Paul L. Rietjens, Ivonne M. C. M. Li, Hequn |
author_facet | van Tongeren, Tessa C. A. Wang, Si Carmichael, Paul L. Rietjens, Ivonne M. C. M. Li, Hequn |
author_sort | van Tongeren, Tessa C. A. |
collection | PubMed |
description | In next generation risk assessment (NGRA), the Dietary Comparator Ratio (DCR) can be used to assess the safety of chemical exposures to humans in a 3R compliant approach. The DCR compares the Exposure Activity Ratio (EAR) for exposure to a compound of interest (EAR(test)) to the EAR for an established safe exposure level to a comparator compound (EAR(comparator)), acting by the same mode of action. It can be concluded that the exposure to a test compound is safe at a corresponding DCR ≤ 1. In this study, genistein (GEN) was selected as a comparator compound by comparison of reported safe internal exposures to GEN to its BMCL(05), as no effect level, the latter determined in the in vitro estrogenic MCF7/Bos proliferation, T47D ER-CALUX, and U2OS ERα-CALUX assay. The EAR(comparator) was defined using the BMCL(05) and EC(50) values from the 3 in vitro assays and subsequently used to calculate the DCRs for exposures to 14 test compounds, predicting the (absence of) estrogenicity. The predictions were evaluated by comparison to reported in vivo estrogenicity in humans for these exposures. The results obtained support in the DCR approach as an important animal-free new approach methodology (NAM) in NGRA and show how in vitro assays can be used to define DCR values. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-023-03480-w. |
format | Online Article Text |
id | pubmed-10182946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-101829462023-05-15 Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays van Tongeren, Tessa C. A. Wang, Si Carmichael, Paul L. Rietjens, Ivonne M. C. M. Li, Hequn Arch Toxicol Regulatory Toxicology In next generation risk assessment (NGRA), the Dietary Comparator Ratio (DCR) can be used to assess the safety of chemical exposures to humans in a 3R compliant approach. The DCR compares the Exposure Activity Ratio (EAR) for exposure to a compound of interest (EAR(test)) to the EAR for an established safe exposure level to a comparator compound (EAR(comparator)), acting by the same mode of action. It can be concluded that the exposure to a test compound is safe at a corresponding DCR ≤ 1. In this study, genistein (GEN) was selected as a comparator compound by comparison of reported safe internal exposures to GEN to its BMCL(05), as no effect level, the latter determined in the in vitro estrogenic MCF7/Bos proliferation, T47D ER-CALUX, and U2OS ERα-CALUX assay. The EAR(comparator) was defined using the BMCL(05) and EC(50) values from the 3 in vitro assays and subsequently used to calculate the DCRs for exposures to 14 test compounds, predicting the (absence of) estrogenicity. The predictions were evaluated by comparison to reported in vivo estrogenicity in humans for these exposures. The results obtained support in the DCR approach as an important animal-free new approach methodology (NAM) in NGRA and show how in vitro assays can be used to define DCR values. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-023-03480-w. Springer Berlin Heidelberg 2023-04-22 2023 /pmc/articles/PMC10182946/ /pubmed/37087486 http://dx.doi.org/10.1007/s00204-023-03480-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Regulatory Toxicology van Tongeren, Tessa C. A. Wang, Si Carmichael, Paul L. Rietjens, Ivonne M. C. M. Li, Hequn Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title | Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title_full | Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title_fullStr | Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title_full_unstemmed | Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title_short | Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
title_sort | next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays |
topic | Regulatory Toxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182946/ https://www.ncbi.nlm.nih.gov/pubmed/37087486 http://dx.doi.org/10.1007/s00204-023-03480-w |
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