Evaluation of the applicability of existing (Q)SAR models for predicting the genotoxicity of pesticides and similarity analysis related with genotoxicity of pesticides for facilitating of grouping and read across

dietaryrisk assessment, genotoxicity, in silico, metabolite, pesticide active substance, (Q)SAR, Read Across
First published in EFSA Supporting Publications
21 March 2019
12 March 2019
External Scientific Report

The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.


To facilitate the practical implementation of the guidance on the residue definition for dietary risk assessment, EFSA has organized an evaluation of applicability of existing in silico models for predicting the genotoxicity of pesticides and their metabolites, including analysis of the impact on genotoxicity of the metabolic structural changes. The prediction ability of (Q)SARs for in vitro and in vivo tests were evaluated. For the Ames test, all (Q)SAR models generated statistically significant predictions, comparable with the experimental variability of the test; instead, the reliability of the (Q)SAR models for assays / endpoints different from in vitro bacterial mutagenicity appears to be quite far from optimality. Secondly, two new Read Across approaches were applied to predict Ames mutagenicity and in vitro Chromosomal Aberrations: Read Across was largely successful for predicting the Ames test results, but much less for in vitro Chromosomal Aberrations. The worse results for endpoints different from Ames may be attributable to the several revisions of experimental protocols and evaluation criteria of results that have made the databases qualitatively non‐homogeneous, and poorly suitable for modelling. A third dimension of this research is the evaluation of the impact of the structural changes‐in result of metabolic or degradation processes‐on the genotoxic potential of the substances. Parent/Metabolite structural differences (beyond the known Structural Alerts) that may, or may not cause changes in the Ames mutagenicity were identified and catalogued. In addition, Structural Alerts analysis applied under human expert supervision permitted the rationalization of the large majority of the changes of patterns of genotoxicity. The findings from this work are suitable for being integrated into Weight‐of‐Evidence and Tiered evaluation schemes. The importance of the human expert knowledge is particularly emphasized.

pesticides.peerreview [at] efsa.europa.eu
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