Cumulative Risk Assessment of Pesticide Residues in Food

There is increasing need to address the potential risks of combined exposures to multiple residues frompesticides in the diet. The available evidence suggests that the main concern is fromdose addition of thosecompounds that act by the same mode of action. The possibility of synergy needs to be addressed on acase-by-case basis, where there is a biologically plausible hypothesis that it may occur at the levels ofresidues occurring in the diet.Cumulative risk assessment is a resource-intense activity and hence a tiered approach to both toxicologicalevaluation and intake estimation is recommended, and the European Food Safety Authority (EFSA)has recently published such a proposal. Where assessments have already been undertaken by some otherauthority, full advantage should be taken of these, subject of course to considerations of quality andrelevance.Inclusion of compounds in a cumulative assessment group (CAG) should be based on defined criteria,which allow for refinement in a tiered approach. These criteria should include chemical structure,mechanism of pesticidal action, target organ and toxic mode of action.A number of methods are available for cumulating toxicity. These are all inter-related, but some aremathematically more complex than others. The most useful methods, in increasing levels of complexityand refinement, are the hazard index, the reference point index, the Relative Potency Factor method andphysiologically based toxicokinetic modelling, although this lastmethodwould only be considered shoulda highly refined assessment be necessary.Four possible exposure scenarios are of relevance for cumulative risk assessment, acute and chronicexposure in the context of maximum residue level (MRL)-setting, and in relation to exposures from theactual use patterns, respectively. Each can be addressed either deterministically or probabilistically. Strategiesfor dealing with residues belowthe limit of detection, limit of quantification or limit of reporting needto be agreed.A number of probabilistic models are available, but some of there are geographically constrained dueto the underlying datasets used in their construction. Guidance on probabilistic modelling needs to befinalised.Cumulative risk assessments have been performed in a number of countries, on organophosphate insecticidesalone (USA) or together with carbamates (UK, DK, NL), triazines, chloroacetanilides, carbamatesalone (USA), and all pesticides (DE).