Scientific Opinion on Evaluation of the Toxicological Relevance of Pesticide Metabolites for Dietary Risk Assessment


Panel on Plant Protection Products and their Residues
EFSA Journal
EFSA Journal 2012;10(7):2799 [187 pp.].
Possible conflict of interest
One member of the Panel did not participate in parts of the discussion on the subject referred to above because of potential conflicts of interest identified in accordance with the EFSA policy on declarations of interests.
Panel Members
Jos Boesten, Claudia Bolognesi, Theo Brock, Ettore Capri, Anthony Hardy, Andrew Hart, Karen Ildico Hirsch-Ernst, Susanne Hougaard Bennekou, Michael Klein, Robert Luttik, Kyriaki Machera, Angelo Moretto (until January 2011), Bernadette Ossendorp, Annette Petersen, Yolanda Pico, Andreas Schäffer, Paulo Sousa, Walter Steurbaut, Anita Strömberg, Maria Tasheva, Ton van der Linden, Christiane Vleminckx.

EFSA wishes to thank the members of the Working Group on Toxicological Relevance of Pesticide Metabolites: Susan Barlow, Emilio Benfenati, Claudia Bolognesi, Alan Boobis, Karen Ildico Hirsch-Ernst, Susanne Hougaard Bennekou, Kyriaki Machera, Otto Meyer, Angelo Moretto (until January 2011), Andre Muller, Markus Müller, Bernadette Ossendorp, Yolanda Pico, Rebecca Scrivens, Anita Strömberg, Maria Tasheva and Christiane Vleminckx, the hearing experts Albert Bergmann, Ian Dewhurst and Andrew Worth and the EFSA staff Lazlo Bura, Edgars Felkers (until March 2012), Miriam Jacobs, István Sebestyén (until May 2012), Hans Steinkellner and Manuela Tiramani for the support provided to this scientific opinion.

Opinion of the Scientific Committee/Scientific Panel
On request from
Question Number
21 June 2012
Published in the EFSA Journal
26 July 2012
Last Updated
2 August 2012. This version replaces the previous one/s.
European Food Safety Authority (EFSA), Parma, Italy

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

EFSA will develop a Guidance Document based on the results in this opinion.

Pesticide metabolites, dietary exposure, endocrine disruptor, Quantitative Structure Activity Relationship, (Q)SAR, read-across, stereoisomer , Threshold of Toxicological Concern (TTC)
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