Genotoxicity assessment of chemical mixtures

Simon More; Vasileios Bampidis; Diane Benford; Jos Boesten; Claude Bragard; Thorhallur Halldorsson; Antonio Hernandez-Jerez; Susanne Hougaard-Bennekou; Kostas Koutsoumanis; Hanspeter Naegeli; Søren Saxmose Nielsen; Dieter Schrenk; Vittorio Silano; Dominique Turck; Maged Younes; Gabriele Aquilina; Riccardo Crebelli; Rainer Gürtler; Karen Ildico Hirsch-Ernst; Pasquale Mosesso; Elsa Nielsen; Roland Solecki; Maria Carfì; Carla Martino; Daniela Maurici; Juan Parra Morte; Josef Schlatter

doi:10.2903/j.efsa.2019.5519

Genotoxicity assessment of chemical mixtures

Simon More, Vasileios Bampidis, Diane Benford, Jos Boesten, Claude Bragard, Thorhallur Halldorsson, Antonio Hernandez-Jerez, Susanne Hougaard-Bennekou, Kostas Koutsoumanis, Hanspeter Naegeli, Søren Saxmose Nielsen, Dieter Schrenk, Vittorio Silano, Dominique Turck, Maged Younes, Gabriele Aquilina, Riccardo Crebelli, Rainer Gürtler, Karen Ildico Hirsch-Ernst, Pasquale MosessoElsa Nielsen, Roland Solecki, Maria Carfì, Carla Martino, Daniela Maurici, Juan Parra Morte, Josef Schlatter

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Abstract

The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow-up study should be considered. For negative results in the in vivo follow-up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow-up test(s), it can be concluded that the mixture does raise a concern about genotoxicity.

Original language	English
Article number	e05519
Journal	EFSA Journal
Volume	17
Issue number	1
Number of pages	11
ISSN	1831-4732
DOIs	https://doi.org/10.2903/j.efsa.2019.5519
Publication status	Published - 1 Jan 2019

Keywords

genotoxicity assessment
chemical mixtures
uncertainty analysis

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10.2903/j.efsa.2019.5519Licence: CC BY-ND

Genotoxicity assessment of chemical mixturesFinal published version, 1.19 MBLicence: CC BY-ND

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More, S., Bampidis, V., Benford, D., Boesten, J., Bragard, C., Halldorsson, T., Hernandez-Jerez, A., Hougaard-Bennekou, S., Koutsoumanis, K., Naegeli, H., Nielsen, S. S., Schrenk, D., Silano, V., Turck, D., Younes, M., Aquilina, G., Crebelli, R., Gürtler, R., Hirsch-Ernst, K. I., ... Schlatter, J. (2019). Genotoxicity assessment of chemical mixtures. EFSA Journal, 17(1), [e05519]. https://doi.org/10.2903/j.efsa.2019.5519

More, S, Bampidis, V, Benford, D, Boesten, J, Bragard, C, Halldorsson, T, Hernandez-Jerez, A, Hougaard-Bennekou, S, Koutsoumanis, K, Naegeli, H, Nielsen, SS, Schrenk, D, Silano, V, Turck, D, Younes, M, Aquilina, G, Crebelli, R, Gürtler, R, Hirsch-Ernst, KI, Mosesso, P, Nielsen, E, Solecki, R, Carfì, M, Martino, C, Maurici, D, Parra Morte, J & Schlatter, J 2019, 'Genotoxicity assessment of chemical mixtures', EFSA Journal, vol. 17, no. 1, e05519. https://doi.org/10.2903/j.efsa.2019.5519

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abstract = "The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow-up study should be considered. For negative results in the in vivo follow-up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow-up test(s), it can be concluded that the mixture does raise a concern about genotoxicity.",

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AU - Bampidis, Vasileios

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AU - Boesten, Jos

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AU - Halldorsson, Thorhallur

AU - Hernandez-Jerez, Antonio

AU - Hougaard-Bennekou, Susanne

AU - Koutsoumanis, Kostas

AU - Naegeli, Hanspeter

AU - Nielsen, Søren Saxmose

AU - Schrenk, Dieter

AU - Silano, Vittorio

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 - Solecki, Roland

AU - Carfì, Maria

AU - Martino, Carla

AU - Maurici, Daniela

AU - Parra Morte, Juan

AU - Schlatter, Josef

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N2 - The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow-up study should be considered. For negative results in the in vivo follow-up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow-up test(s), it can be concluded that the mixture does raise a concern about genotoxicity.

AB - The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow-up study should be considered. For negative results in the in vivo follow-up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow-up test(s), it can be concluded that the mixture does raise a concern about genotoxicity.

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KW - uncertainty analysis

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DO - 10.2903/j.efsa.2019.5519

M3 - Journal article

C2 - 32626066

SN - 1831-4732

VL - 17

JO - E F S A Journal

JF - E F S A Journal

IS - 1

M1 - e05519

ER -

Genotoxicity assessment of chemical mixtures

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