Guidance on aneugenicity assessment

Research output: Contribution to journal › Journal article › Research

Standard

Guidance on aneugenicity assessment. / EFSA Scientific Committee; More, Simon John; Bampidis, Vasileios; Bragard, Claude; Halldorsson, Thorhallur Ingi; Hernández-Jerez, Antonio F; Hougaard Bennekou, Susanne; Koutsoumanis, Kostas; Lambré, Claude; Machera, Kyriaki; Naegeli, Hanspeter; Nielsen, Søren Saxmose; Schlatter, Josef; Schrenk, Dieter; Turck, Dominique; Younes, Maged; Aquilina, Gabriele; Bignami, Margherita; Bolognesi, Claudia; Crebelli, Riccardo; Gürtler, Rainer; Marcon, Francesca; Nielsen, Elsa; Vleminckx, Christiane; Carfì, Maria; Martino, Carla; Maurici, Daniela; Parra Morte, Juan; Rossi, Annamaria; Benford, Diane.

In: EFSA Journal, Vol. 19, No. 8, e06770, 2021, p. 1-27.

Research output: Contribution to journal › Journal article › Research

Harvard

EFSA Scientific Committee, More, SJ, Bampidis, V, Bragard, C, Halldorsson, TI, Hernández-Jerez, AF, Hougaard Bennekou, S, Koutsoumanis, K, Lambré, C, Machera, K, Naegeli, H, Nielsen, SS, Schlatter, J, Schrenk, D, Turck, D, Younes, M, Aquilina, G, Bignami, M, Bolognesi, C, Crebelli, R, Gürtler, R, Marcon, F, Nielsen, E, Vleminckx, C, Carfì, M, Martino, C, Maurici, D, Parra Morte, J, Rossi, A & Benford, D 2021, 'Guidance on aneugenicity assessment', EFSA Journal, vol. 19, no. 8, e06770, pp. 1-27. https://doi.org/10.2903/j.efsa.2021.6770

APA

EFSA Scientific Committee, More, S. J., Bampidis, V., Bragard, C., Halldorsson, T. I., Hernández-Jerez, A. F., Hougaard Bennekou, S., Koutsoumanis, K., Lambré, C., Machera, K., Naegeli, H., Nielsen, S. S., Schlatter, J., Schrenk, D., Turck, D., Younes, M., Aquilina, G., Bignami, M., Bolognesi, C., ... Benford, D. (2021). Guidance on aneugenicity assessment. EFSA Journal, 19(8), 1-27. [e06770]. https://doi.org/10.2903/j.efsa.2021.6770

Vancouver

EFSA Scientific Committee, More SJ, Bampidis V, Bragard C, Halldorsson TI, Hernández-Jerez AF et al. Guidance on aneugenicity assessment. EFSA Journal. 2021;19(8):1-27. e06770. https://doi.org/10.2903/j.efsa.2021.6770

Author

EFSA Scientific Committee ; More, Simon John ; Bampidis, Vasileios ; Bragard, Claude ; Halldorsson, Thorhallur Ingi ; Hernández-Jerez, Antonio F ; Hougaard Bennekou, Susanne ; Koutsoumanis, Kostas ; Lambré, Claude ; Machera, Kyriaki ; Naegeli, Hanspeter ; Nielsen, Søren Saxmose ; Schlatter, Josef ; Schrenk, Dieter ; Turck, Dominique ; Younes, Maged ; Aquilina, Gabriele ; Bignami, Margherita ; Bolognesi, Claudia ; Crebelli, Riccardo ; Gürtler, Rainer ; Marcon, Francesca ; Nielsen, Elsa ; Vleminckx, Christiane ; Carfì, Maria ; Martino, Carla ; Maurici, Daniela ; Parra Morte, Juan ; Rossi, Annamaria ; Benford, Diane. / Guidance on aneugenicity assessment. In: EFSA Journal. 2021 ; Vol. 19, No. 8. pp. 1-27.

Bibtex

@article{56f2763e1d18490c93542f910a6e1c24,
title = "Guidance on aneugenicity assessment",
abstract = "Abstract The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment.",
keywords = "aneugenicity, micronucleus test, genotoxicity in vivo and in vitro",
author = "{EFSA Scientific Committee} and More, {Simon John} and Vasileios Bampidis and Claude Bragard and Halldorsson, {Thorhallur Ingi} and Hern{\'a}ndez-Jerez, {Antonio F} and {Hougaard Bennekou}, Susanne and Kostas Koutsoumanis and Claude Lambr{\'e} and Kyriaki Machera and Hanspeter Naegeli and Nielsen, {S{\o}ren Saxmose} and Josef Schlatter and Dieter Schrenk and Dominique Turck and Maged Younes and Gabriele Aquilina and Margherita Bignami and Claudia Bolognesi and Riccardo Crebelli and Rainer G{\"u}rtler and Francesca Marcon and Elsa Nielsen and Christiane Vleminckx and Maria Carf{\`i} and Carla Martino and Daniela Maurici and {Parra Morte}, Juan and Annamaria Rossi and Diane Benford",
year = "2021",
doi = "10.2903/j.efsa.2021.6770",
language = "English",
volume = "19",
pages = "1--27",
journal = "E F S A Journal",
issn = "1831-4732",
publisher = "European Food Safety Authority (E F S A)",
number = "8",

}

RIS

TY - JOUR

T1 - Guidance on aneugenicity assessment

AU - EFSA Scientific Committee, null

AU - More, Simon John

AU - Bampidis, Vasileios

AU - Bragard, Claude

AU - Halldorsson, Thorhallur Ingi

AU - Hernández-Jerez, Antonio F

AU - Hougaard Bennekou, Susanne

AU - Koutsoumanis, Kostas

AU - Lambré, Claude

AU - Machera, Kyriaki

AU - Naegeli, Hanspeter

AU - Nielsen, Søren Saxmose

AU - Schlatter, Josef

AU - Schrenk, Dieter

AU - Turck, Dominique

AU - Younes, Maged

AU - Aquilina, Gabriele

AU - Bignami, Margherita

AU - Bolognesi, Claudia

AU - Crebelli, Riccardo

AU - Gürtler, Rainer

AU - Marcon, Francesca

AU - Nielsen, Elsa

AU - Vleminckx, Christiane

AU - Carfì, Maria

AU - Martino, Carla

AU - Maurici, Daniela

AU - Parra Morte, Juan

AU - Rossi, Annamaria

AU - Benford, Diane

PY - 2021

Y1 - 2021

N2 - Abstract The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment.

AB - Abstract The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment.

KW - aneugenicity

KW - micronucleus test

KW - genotoxicity in vivo and in vitro

U2 - 10.2903/j.efsa.2021.6770

DO - 10.2903/j.efsa.2021.6770

M3 - Journal article

C2 - 34386097

VL - 19

SP - 1

EP - 27

JO - E F S A Journal

JF - E F S A Journal

SN - 1831-4732

IS - 8

M1 - e06770

ER -

ID: 275766020