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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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.
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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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