Metabolites in the regulatory risk assessment of pesticides in the EU

A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. In the pharmaceutical arena, metabolism and metabolites are being studied from the very early stages of drug development and they are of significance in pharmacokinetics and the definition of first-drug in man, drug-drug interactions and drug-induced adversities. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of toxicological studies, assessing pesticide-associated issues in (eco)toxicology for hazard characterization and One Health risk assessment purposes. This is of particular relevance to pesticide metabolites that are unique or disproportionate in humans in comparison with metabolites found in in vitro or in vivo animal studies, underlying potential toxicological concerns. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both kinetics and dynamics. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.

PELKONEN Olavi;  ABASS Khaled;  PARRA MORTE Juan;  PANZAREA Martina;  TESTAI Emanuela;  RUDAZ Serge;  LOUISSE Jochem;  GUNDERT-REMY Ursula;  WOLTERINK Gerrit;  DORNE Jean-Lou;  COECKE Sandra;  BERNASCONI Camilla; 

2024-11-06

FRONTIERS MEDIA SA

JRC136165

2673-3080 (online),   

https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2023.1304885,    https://publications.jrc.ec.europa.eu/repository/handle/JRC136165,   

10.3389/ftox.2023.1304885 (online),