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Summary

The ACROPOLIS consortium

ACROPOLIS stands for Aggregate and Cumulative Risk Of Pesticides: an On-Line Integrated Strategy. The overall objective of the ACROPOLIS project is to improve risk assessment strategies in Europe. In this project a framework for cumulative and aggregate risk assessment of pesticides was developed that is scientifically sound and accessible for all actors involved in the European risk assessment and risk management. The specific objectives of the project were:

  1. Improving cumulative exposure assessment methodology;
  2. Devising new models for aggregate exposure assessment addressing different routes of exposure;
  3. Testing the feasibility of using in vitro methods to refine cumulative assessment groups and to assess the outcome of combined exposures. In particular to confirm or discount the dose-additivity hypothesis for compounds having a similar mode of action.
  4. Integrating single-compound, cumulative and aggregate risk models in a web-based tool, including accessible data for all stakeholders;
  5. Improving the understanding of cumulative and aggregated e risk assessment methodology by different stakeholders.

Cumulative exposure model

Within the ACROPOLIS project a model was developed to assess the dietary cumulative exposure to compounds belonging to a cumulative assessment group (CAG). In 2012 EFSA published a guidance in which the framework of performing probabilistic dietary exposure assessments (both single and multiple compound) has been set out. In this EFSA Guidance an optimistic and pessimistic model run are proposed aiming, respectively, at estimating the possible lower and upper range of exposures in a population. For assessing cumulative dietary exposures, both the EFSA Guidance methods as well as other more refined models have been implemented in the web-based Monte Carlo Risk Assessment (MCRA) system.

To test the implementation of the EFSA Guidance methods in the MCRA system, cumulative dietary exposure assessments were performed within the project. These assessments were performed to test both the implementation as well as the practicality of the EFSA Guidance methods. For this, the cumulative exposure to two CAGs of triazole pesticides was estimated using national food consumption and monitoring data of several European countries. The food consumption data were obtained from the EFSA Comprehensive database. Processing factors were obtained from the BfR (Bundesinstitut fur Risikobewertung) database and supplemented with additional information from Draft Assessment Reports. The observed gaps in concentration data were filled as required by the EFSA Guidance. It was concluded that the implementation worked very well and that application of the optimistic model run was feasible, resulting however in underestimates of the real exposure. The pessimistic model run, on the other hand, may severely overestimate the exposure. Especially the inclusion of maximum residue limits (MRLs) of unmeasured animal commodities seemed to result in unrealistic conclusions regarding the contribution of animal commodities to the dietary exposure. A conclusion may be that some kind of intermediate scenario, more realistic than either the optimistic or the pessimistic scenario, is needed. Such a ‘realistic’ scenario would combine the available optimistic and pessimistic options and possibly include some of the new options developed in ACROPOLIS to provide exposures that in case of missing information still can be argued to be conservative (precautionary principle) but not over-conservative, as now seems the case with the pessimistic model run.

Apart from practicalities to get external data connected and open issues for risk management, the cumulative ACROPOLIS model was well-received throughout Europe and many member states and stakeholders are presently making use of the model. Performing cumulative dietary exposure assessment, including uncertainty analyses, can be performed on-line, which is an innovation. Extensive drill-down information is available to check the realism of the performed calculations in relation to the modelling assumptions made. The current system works well with the currently available datasets, but may need further testing once CAGs become larger or when exposure to mixtures needs to be applied with the full European data collection on a routine basis.

Aggregate exposure

Aggregate exposure combines dietary and non-dietary sources of exposure, which is relevant for pesticide residues. Examples of non-dietary exposure to these chemicals are exposure through occupational farming activities, the use of consumer products, or incidental exposures experienced by residents of farms or bystanders. All these individuals are also exposed to pesticide residues via food. The conceptual framework of aggregated exposure was implemented in the MCRA system and tested addressing four different aggregated exposure scenarios in the form of case studies. Further testing and validation is recommended.

Both the cumulative and the aggregate models were validated, and are transparent and fully documented. Validation was performed against simulated data where the true outcome in known, and against the factor standard program used by the US-EPA, namely DEEM-FCID.

Testing of in vitro models

The ACROPOLIS project has delivered two useful in vitro test systems and two PB-PK (physiologically based pharmacokinetic) models to extrapolate external dose information from the MCRA system to internal dose effects based on the toxico-kinetics and toxico-dynamics of the compounds in the mixture. In vitro test were used to express the dose relationship and their combined effect for different compounds and mixtures of compounds belonging to the same CAG. To extrapolate these in vitro results to a potential hazardous effect in the human body, PB-PK modelling was used and found very useful. PB-PK modelling techniques are also helpful to extrapolate from animals to humans. In the context of cumulative risk assessment, in vitro studies as performed in the ACROPOLIS project have been proven extremely valuable for both refinement of grouping and confirmation of the dose-additivity assumption.

Stakeholders attitudes

Qualitative and quantitative analyses of stakeholders’ attitudes, understanding and willingness to accept new advanced models for cumulative and aggregate exposure was tested. The result of this analysis was that the relevance and expected outcomes of ACROPOLIS’ were perceived favourably. Stakeholders generally called for targeted information, dissemination and training programmes in relation to the proposed cumulative and aggregate pesticide exposure assessment methods and tools. The research defined barriers and challenges, which we have transferred into practice by providing training. Furthermore, we achieved a worldwide dissemination and interaction with relevant authorities in and outside Europe.

Acknowledgement: EU grant agreement EU-FP7 KBBE-2009 No. 245163.