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Clarification of some aspects related to genotoxicity assessment
The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow‐up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly i...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009892/ https://www.ncbi.nlm.nih.gov/pubmed/32625393 http://dx.doi.org/10.2903/j.efsa.2017.5113 |
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author | Hardy, Anthony Benford, Diane Halldorsson, Thorhallur Jeger, Michael Knutsen, Helle Katrine More, Simon Naegeli, Hanspeter Noteborn, Hubert Ockleford, Colin Ricci, Antonia Rychen, Guido Silano, Vittorio Solecki, Roland Turck, Dominique Younes, Maged Aquilina, Gabriele Crebelli, Riccardo Gürtler, Rainer Hirsch‐Ernst, Karen Ildico Mosesso, Pasquale Nielsen, Elsa van Benthem, Jan Carfì, Maria Georgiadis, Nikolaos Maurici, Daniela Parra Morte, Juan Schlatter, Josef |
author_facet | Hardy, Anthony Benford, Diane Halldorsson, Thorhallur Jeger, Michael Knutsen, Helle Katrine More, Simon Naegeli, Hanspeter Noteborn, Hubert Ockleford, Colin Ricci, Antonia Rychen, Guido Silano, Vittorio Solecki, Roland Turck, Dominique Younes, Maged Aquilina, Gabriele Crebelli, Riccardo Gürtler, Rainer Hirsch‐Ernst, Karen Ildico Mosesso, Pasquale Nielsen, Elsa van Benthem, Jan Carfì, Maria Georgiadis, Nikolaos Maurici, Daniela Parra Morte, Juan Schlatter, Josef |
collection | PubMed |
description | The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow‐up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight‐of‐evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health‐based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re‐assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight‐of‐evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight‐of‐evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health‐based guidance values may be established. However, if concerns for genotoxicity remain, establishing health‐based guidance values is not considered appropriate. |
format | Online Article Text |
id | pubmed-7009892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70098922020-07-02 Clarification of some aspects related to genotoxicity assessment Hardy, Anthony Benford, Diane Halldorsson, Thorhallur Jeger, Michael Knutsen, Helle Katrine More, Simon Naegeli, Hanspeter Noteborn, Hubert Ockleford, Colin Ricci, Antonia Rychen, Guido Silano, Vittorio Solecki, Roland Turck, Dominique Younes, Maged Aquilina, Gabriele Crebelli, Riccardo Gürtler, Rainer Hirsch‐Ernst, Karen Ildico Mosesso, Pasquale Nielsen, Elsa van Benthem, Jan Carfì, Maria Georgiadis, Nikolaos Maurici, Daniela Parra Morte, Juan Schlatter, Josef EFSA J Scientific Opinion The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow‐up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight‐of‐evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health‐based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re‐assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight‐of‐evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight‐of‐evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health‐based guidance values may be established. However, if concerns for genotoxicity remain, establishing health‐based guidance values is not considered appropriate. John Wiley and Sons Inc. 2017-12-18 /pmc/articles/PMC7009892/ /pubmed/32625393 http://dx.doi.org/10.2903/j.efsa.2017.5113 Text en © 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. |
spellingShingle | Scientific Opinion Hardy, Anthony Benford, Diane Halldorsson, Thorhallur Jeger, Michael Knutsen, Helle Katrine More, Simon Naegeli, Hanspeter Noteborn, Hubert Ockleford, Colin Ricci, Antonia Rychen, Guido Silano, Vittorio Solecki, Roland Turck, Dominique Younes, Maged Aquilina, Gabriele Crebelli, Riccardo Gürtler, Rainer Hirsch‐Ernst, Karen Ildico Mosesso, Pasquale Nielsen, Elsa van Benthem, Jan Carfì, Maria Georgiadis, Nikolaos Maurici, Daniela Parra Morte, Juan Schlatter, Josef Clarification of some aspects related to genotoxicity assessment |
title | Clarification of some aspects related to genotoxicity assessment |
title_full | Clarification of some aspects related to genotoxicity assessment |
title_fullStr | Clarification of some aspects related to genotoxicity assessment |
title_full_unstemmed | Clarification of some aspects related to genotoxicity assessment |
title_short | Clarification of some aspects related to genotoxicity assessment |
title_sort | clarification of some aspects related to genotoxicity assessment |
topic | Scientific Opinion |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009892/ https://www.ncbi.nlm.nih.gov/pubmed/32625393 http://dx.doi.org/10.2903/j.efsa.2017.5113 |
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