Metabolites in the regulatory risk assessment of pesticides in the EU
Pelkonen, Olavi; Abass, Khaled; Parra Morte, Juan Manuel; Panzarea, Martina; Testai, Emanuela; Rudaz, Serge; Louisse, Jochem; Gundert-Remy, Ursula; Wolterink, Gerrit; Jean-Lou CM, Dorne; Coecke, Sandra; Bernasconi, Camilla (2023-12-19)
Frontiers Media
19.12.2023
Pelkonen O, Abass K, Parra Morte JM, Panzarea M, Testai E, Rudaz S, Louisse J, Gundert-Remy U, Wolterink G, Jean-Lou CM D, Coecke S and Bernasconi C (2023), Metabolites in the regulatory risk assessment of pesticides in the EU. Front. Toxicol. 5:1304885. doi: 10.3389/ftox.2023.1304885.
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© 2023 Pelkonen, Abass, Parra Morte, Panzarea, Testai, Rudaz, Louisse, Gundert-Remy, Wolterink, Jean-Lou CM, Coecke and Bernasconi. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
© 2023 Pelkonen, Abass, Parra Morte, Panzarea, Testai, Rudaz, Louisse, Gundert-Remy, Wolterink, Jean-Lou CM, Coecke and Bernasconi. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202401121200
https://urn.fi/URN:NBN:fi:oulu-202401121200
Tiivistelmä
Abstract
A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities. This is of particular relevance to pesticide metabolites that are unique to humans in comparison with metabolites found in in vitro or in vivo animal studies, but also to disproportionate metabolites (quantitative differences) between humans and mammalian species. Presence of unique or disproportionate metabolites may underlie potential toxicological concerns. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for hazard and risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.
A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities. This is of particular relevance to pesticide metabolites that are unique to humans in comparison with metabolites found in in vitro or in vivo animal studies, but also to disproportionate metabolites (quantitative differences) between humans and mammalian species. Presence of unique or disproportionate metabolites may underlie potential toxicological concerns. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for hazard and risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.
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