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Synergistic effects of chemical mixtures: how frequent is rare?

Martin, Olwenn V; (2023) Synergistic effects of chemical mixtures: how frequent is rare? Current Opinion in Toxicology , Article 100424. 10.1016/j.cotox.2023.100424. (In press). Green open access

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Abstract

Chemical pollution is characterised by sequential and simultaneous exposure to unintentional complex mixtures. The almost infinite number of real-life mixtures poses major challenges for investigations of all possible exposure scenarios through whole mixture or component-based approaches. As a pragmatic approach in data-poor situations, the application of a Mixture Assessment Factor to single substances assessments under REACH was announced in the European Chemicals Strategy for Sustainability. Current proposals for this factor are based on the assumption that mixtures behave additively, assuming that synergistic interactions are rare. This assumption is based on eight reviews published in the last 30 years. Synergistic deviations from additivity greater than 2-fold were reported in roughly 5% of investigated mixtures. This was more, rather than less, frequent in the handful of suitable studies of low dose mammalian mixture toxicity. This frequency is representative of mixtures toxicology studies in the literature and should not be interpreted as the frequency of synergisms in real world exposures. Understanding the frequency and likelihood of synergisms would entail detailed understanding of the co-occurrence of groups of substances giving rise to such interactions in relevant environmental media. Assumptions that synergistic interactions in real-life mixtures are rare appear to be premature. While further research is required, potential synergisms should not be omitted from debates on the conservatism or otherwise of mixture allocation factor or other regulatory approaches to protect people and environment from mixture effects.

Type: Article
Title: Synergistic effects of chemical mixtures: how frequent is rare?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cotox.2023.100424
Publisher version: https://doi.org/10.1016/j.cotox.2023.100424
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Chemical mixtures, synergism, mixture assessment factor, mixture allocation factor, MAF, interaction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL SLASH
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities > Arts and Sciences (BASc)
URI: https://discovery.ucl.ac.uk/id/eprint/10175578
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