Matched molecular pairs-driven read-across for the prediction of genotoxicity of plant protection product residues

Abstract

In dietary risk assessment of plant protection products, residues of active ingredients and their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. To characterise similarity, a matched molecular pairs approach has been developed and applied to datasests of sulphonylurea herbicides, strobilurins fungicides and α-chloroacetamide herbicides for which either Ames, chromosomal aberration or micronucleus test results are publicly available. The approach is exemplified with four case studies illustrating how matched molecular pairs analysis can be used to identify analogues that cover the structural domain of the chemical for which a data-gap exists. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing.