The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and theirResidues (PPR) to develop an opinion on approaches to evaluate the toxicological relevance ofmetabolites and degradates of pesticide active substances in dietary risk assessment. This opinionidentifies the threshold of toxicological concern (TTC) concept as an appropriate screening tool. TheTTC values for genotoxic and toxic compounds were found to be sufficiently conservative for chronicexposure, as a result of a validation study with a group of pesticides belonging to different chemicalclasses. Three critical steps were identified in the application of a TTC scheme: 1) the estimate of thelevel of the metabolite, 2) the evaluation of genotoxicity alerts and 3) the detection of neurotoxicmetabolites. Tentative TTC values for acute exposure were established by the PPR Panel by analysisof the lowest 5th percentiles of No Observed Adverse Effect Levels (NOAELs) used to establish theAcute Reference Doses (ARfD) for the EFSA pesticide data set. Assessment schemes for chronic andacute dietary risk assessment of pesticide metabolites, using the TTC approach and combined (Q)SARand read across, are proposed. The opinion also proposes how the risk assessment of pesticidemetabolites that are stereoisomers should be addressed due to isomer ratio changes reflected in thecomposition of metabolites. The approach is ready for use, but it is anticipated that on many occasionsthe outcome of the assessment scheme will be that further testing is needed to reach a firm conclusionon the toxicological relevance of the metabolite. However, the benefit of applying the approach is thatit will allow prioritisation of metabolites for subsequent testing.EFSA will develop a Guidance Document based on the results in this opinion.