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Clarification of some aspects related to genotoxicity assessment

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Clarification of some aspects related to genotoxicity assessment. / Hardy, Anthony; Benford, Diane; Halldorsson, Thorhallur et al.
In: EFSA Journal, Vol. 15, No. 12, 05113, 12.2017.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Hardy, A, Benford, D, Halldorsson, T, Jeger, M, Knutsen, HK, More, S, Naegeli, H, Noteborn, H, Ockleford, C, Ricci, A, Rychen, G, Silano, V, Solecki, R, Turck, D, Younes, M, Aquilina, G, Crebelli, R, Gürtler, R, Hirsch-Ernst, KI, Mosesso, P, Nielsen, E, van Benthem, J, Carfì, M, Georgiadis, N, Maurici, D, Parra Morte, J & Schlatter, J 2017, 'Clarification of some aspects related to genotoxicity assessment', EFSA Journal, vol. 15, no. 12, 05113. https://doi.org/10.2903/j.efsa.2017.5113

APA

Hardy, A., Benford, D., Halldorsson, T., Jeger, M., Knutsen, H. K., More, S., Naegeli, H., Noteborn, H., Ockleford, C., Ricci, A., Rychen, G., Silano, V., Solecki, R., Turck, D., Younes, M., Aquilina, G., Crebelli, R., Gürtler, R., Hirsch-Ernst, K. I., ... Schlatter, J. (2017). Clarification of some aspects related to genotoxicity assessment. EFSA Journal, 15(12), Article 05113. https://doi.org/10.2903/j.efsa.2017.5113

Vancouver

Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S et al. Clarification of some aspects related to genotoxicity assessment. EFSA Journal. 2017 Dec;15(12):05113. Epub 2017 Dec 18. doi: 10.2903/j.efsa.2017.5113

Author

Hardy, Anthony ; Benford, Diane ; Halldorsson, Thorhallur et al. / Clarification of some aspects related to genotoxicity assessment. In: EFSA Journal. 2017 ; Vol. 15, No. 12.

Bibtex

@article{aa0e500c738d4ebba699fb4c40c51d06,
title = "Clarification of some aspects related to genotoxicity assessment",
abstract = "Abstract 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.",
keywords = "genotoxicity, in vivo UDS assay, micronucleus test, weight-of-evidence, bone marrow exposure",
author = "Anthony Hardy and Diane Benford and Thorhallur Halldorsson and Michael Jeger and Knutsen, {Helle Katrine} and Simon More and Hanspeter Naegeli and Hubert Noteborn and Colin Ockleford and Antonia Ricci and Guido Rychen and Vittorio Silano and Roland Solecki and Dominique Turck and Maged Younes and Gabriele Aquilina and Riccardo Crebelli and Rainer G{\"u}rtler and Hirsch-Ernst, {Karen Ildico} and Pasquale Mosesso and Elsa Nielsen and {van Benthem}, Jan and Maria Carf{\`i} and Nikolaos Georgiadis and Daniela Maurici and {Parra Morte}, Juan and Josef Schlatter",
year = "2017",
month = dec,
doi = "10.2903/j.efsa.2017.5113",
language = "English",
volume = "15",
journal = "EFSA Journal",
issn = "1831-4732",
publisher = "John Wiley & Sons, Ltd",
number = "12",

}

RIS

TY - JOUR

T1 - Clarification of some aspects related to genotoxicity assessment

AU - Hardy, Anthony

AU - Benford, Diane

AU - Halldorsson, Thorhallur

AU - Jeger, Michael

AU - Knutsen, Helle Katrine

AU - More, Simon

AU - Naegeli, Hanspeter

AU - Noteborn, Hubert

AU - Ockleford, Colin

AU - Ricci, Antonia

AU - Rychen, Guido

AU - Silano, Vittorio

AU - Solecki, Roland

AU - Turck, Dominique

AU - Younes, Maged

AU - Aquilina, Gabriele

AU - Crebelli, Riccardo

AU - Gürtler, Rainer

AU - Hirsch-Ernst, Karen Ildico

AU - Mosesso, Pasquale

AU - Nielsen, Elsa

AU - van Benthem, Jan

AU - Carfì, Maria

AU - Georgiadis, Nikolaos

AU - Maurici, Daniela

AU - Parra Morte, Juan

AU - Schlatter, Josef

PY - 2017/12

Y1 - 2017/12

N2 - Abstract 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.

AB - Abstract 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.

KW - genotoxicity

KW - in vivo UDS assay

KW - micronucleus test

KW - weight-of-evidence

KW - bone marrow exposure

U2 - 10.2903/j.efsa.2017.5113

DO - 10.2903/j.efsa.2017.5113

M3 - Journal article

VL - 15

JO - EFSA Journal

JF - EFSA Journal

SN - 1831-4732

IS - 12

M1 - 05113

ER -