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This report gives a complete description of the current information flow for pesticide related metabolism studies, the relevant terms and concepts, the tools that are used and the data collection system. Based on a critical analysis supported by a survey, the BfR developed proposals for short and long-term improvements of the information flow. The proposal contains ideas for improvement of the MetaPath software package and the use of it in the context of pesticide applications with IUCLID. This document is also a collection of user requirements, not necessarily formulated with one concrete technical solution. Different technical solutions are also proposed and BfR made an analysis of the pros and cons of these solutions. This document (available in pdf format and in zip file including attachments) is meant to support a decision process but should not be considered as defined action plan. For any question related to the report, please contact https://connect.efsa.europa.eu/RM/s/new-ask-efsa-request, DE; PDF; pesticides.mrl@efsa.europa.eu

Following a request from EFSA, the Panel on Plant Protection Products and their Residues developed an opinion on the science to support the potential development of a risk assessment scheme of plant protection products for amphibians and reptiles. The coverage of the risk to amphibians and reptiles by current risk assessments for other vertebrate groups was investigated. Available test methods and exposure models were reviewed with regard to their applicability to amphibians and reptiles. Proposals were made for specific protection goals aiming to protect important ecosystem services and taking into consideration the regulatory framework and existing protection goals for other vertebrates. Uncertainties, knowledge gaps and research needs were highlighted.

The Panel has interpreted the Terms of Reference by carrying out a stepwise evaluation of the BEEHAVE simulation model with a view to assessing its suitability for use in a regulatory context and for risk assessment of multiple stressors at the landscape level. The EFSA opinion on good modelling practice was used to evaluate the model and its documentation systematically. The overall conclusion is that BEEHAVE performs well in modelling honeybee colony dynamics, and the supporting documentation is generally good but does not fully meet the criteria of the good modelling opinion. BEEHAVE is not yet usable in a regulatory context primarily because it needs a pesticide module. BEEHAVE has a Varroa/virus module, although this seems to underestimate the impact of Varroa/virus on colony survival, and additional stressors (chemical and biological) would need to be added to allow investigation of the effects of interactions of pesticides with multiple stressors. BEEHAVE currently uses a very simple representation of a landscape and this should be extended. There is only one environmental scenario in the present version of BEEHAVE (European central zone-weather scenarios for Germany and the UK) and extension to other European zones would be needed. The supporting data and default parameter values should be further evaluated and justified. The modelling environment used by BEEHAVE (NetLogo) has an excellent user interface but provides limited opportunities for extending the model. The Panel recommends that BEEHAVE should be adopted as the basis for modelling the impact on honeybee colonies of pesticides and other stressors, but that further development should use a standard, object-oriented language rather than NetLogo.

Following a request from the European Food Safety Authority, the Panel on Plant Protection Products and their Residues developed an opinion on the science to support the development of a risk assessment scheme of plant protection products for non-target arthropods. The current risk assessment scheme is reviewed, taking into consideration recent workshops and progress in science. Proposals are made for specific protection goals which aim to protect important ecosystem services such as food web support, pest control and biodiversity. In order to address recovery and source-sink population dynamics, conducting a landscape-level risk assessment is suggested. A new risk assessment scheme is suggested which integrates modelling approaches. The main exposure routes for non-target arthropods are identified and proposals are made on how to integrate them in the risk assessment. The appropriateness of the currently used vegetation distribution factor was investigated. It is proposed that new tests be included in order to address exposure via oral uptake of residues and uncertainties related to differences in species sensitivity.

The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their Residues to prepare a scientific opinion on the Food and Environment Research Agency guidance proposal 'Guidance on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessments'. The Panel concluded that the experimental and modelling approaches described in the proposed guidance are reasonable compromises between the required effort and what is desirable from a theoretical point of view. However, the Panel has concerns about the interpretation of the experiments and how the results of the experiments should be used in the leaching assessment. The Panel investigated options for improvement, but could not complete its evaluation on these two topics because underlying data to test these options were not made available to the Panel. For this reason, the Panel prepared a statement instead of a scientific opinion. Therefore, the Panel cannot recommend the use of the guidance for the time being.

The Panel has interpreted the Terms of Reference as a stepwise analysis of issues relevant to both the development and the evaluation of models to assess ecological effects of pesticides. The regulatory model should be selected or developed to address the relevant specific protection goal. The basis of good modelling practice must be the knowledge of relevant processes and the availability of data of sufficient quality. The opinion identifies several critical steps in order to set models within risk assessment, namely: problem formulation, considering the specific protection goals for the taxa or functional groups of concern; model domain of applicability, which drives the species and scenarios to model; species (and life stage) selection, considering relevant life history traits and toxicological/toxicokinetics characteristics of the pesticide; selection of the environmental scenario, which is defined by a combination of abiotic, biotic and agronomic parameters to provide a realistic worst-case situation. Model development should follow the modelling cycle, in which every step has to be fully documented: (i) problem definition; (ii) model formulation, i.e. design of a conceptual model; (iii) model formalisation, in which variables and parameters are linked together into mathematical equations or algorithms; (iv) model implementation, in which a computer code is produced and verified; (v) model setup, including sensitivity analysis, uncertainty analysis and comparison with observed data, that delivers the regulatory model; (vi) prior to actual use in risk assessment, the regulatory model should be evaluated for relevance to the specific protection goals; (vii) feedback from risk assessor with possible recommendations for model improvement. Model evaluation by regulatory authorities should consider each step of the modelling cycle: the opinion identifies points of particular attention for the use of mechanistic effect models in pesticide risk assessment. It is recommended that models be documented in a complete and transparent way, that a feedback platform be established involving risk assessors and model developers, and that a set of agreed models be made available.

Following a request from the European Food Safety Authority, the Panel on Plant Protection Products and their Residues developed an opinion on the science to support the development of a risk assessment scheme of plant (crop) protection products on non-target terrestrial plants (NTTPs). This scientific opinion is largely a literature review on the most up-to-date knowledge of factors influencing phytotoxicity testing and risk assessment of NTTPs. Specific protection goals (SPGs) were defined for off-field, in-field and endangered species. SPGs are closely linked to ecosystem services and functions, and include maintaining provision of water regulation, food web support, aesthetic values, genetic resources and biodiversity. Gaps were identified in standard guidelines currently used in lower tier testing (tier I/II). In these guidelines, tests are conducted at the seedling/juvenile stage using mostly annual crops, and effects are recorded at the juvenile/vegetative stage under greenhouse conditions with plants grown individually or in monoculture. Endpoints measured do not include the overall effect on the whole life cycle (germinating seeds, seedling, juvenile stages, flowering, and seed production and germinability). It is also noted that it is unknown whether the following groups of organisms are covered by the plant risk assessment as it is carried out now: ferns, mosses, liverworts, hornworts, horsetails, lichens or woody species. In terms of exposure, droplet drift is considered to be the most important factor for off-field emissions to non-target areas. Models are available to calculate loadings from spray drift. Higher tier assessment is not required if the risk based on the tier II level can be managed by risk mitigation measures. When required, higher tier tests should be conducted under more realistic conditions. They may include additional laboratory/greenhouse tests (e.g. to measure reproductive endpoints or species interactions), microcosms or field experiments with experimentally or already established species. Other issues were considered, including exposure to mixtures, adjuvants, co-formulants and metabolites. Recommendations for the improvement of current guidelines and the elaboration of new guidelines and risk assessment schemes are provided.

Following a request from the European Commission, the Panel on Plant Protection Products and their Residues (PPR) was asked to deliver a scientific opinion on the report of the FOCUS groundwater working group (FOCUS, 2009) with respect to the higher tier leaching assessments. The PPR Panel is of the general opinion that, as suggested in the FOCUS report, substance parameter refinement can be applied in risk assessment. State of the art knowledge has developed to such an extent that scenario refinement is feasible as well, but will make assessment more complex unless embedded in basic tools and adequate guidance. The same is true for spatial modelling but establishment of adequate databases will require quite some effort. The Panel considers current knowledge on groundwater hydrology insufficient for implementation of monitoring as the highest tier of the assessment at the European level. The implementation of scenario refinement and spatial modelling requires clear criteria on the extent of arable surface areas with estimated leaching rates below the threshold level.

The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their Residues (PPR Panel) to develop a Scientific Opinion on the relevance of dissimilar mode of action and its appropriate application for cumulative risk assessment of pesticides residues in food. The present opinion was preceded by three previous opinions of the PPR Panel (EFSA, 2008, 2009, 2013). The purpose of the present opinion was to assess the relevance of dissimilar modes of action (MoA) for cumulative risk assessment, to evaluate the existing methods for assessing chemicals acting by dissimilar MoA and to identify which methods need to be considered. The PPR Panel restricted its considerations of pesticide combinations with dissimilar modes of action to substances that produce a common adverse effect on the same organ/system. The PPR Panel noted that there is no case documented in the scientific literature where independent action provided more conservative predictions of combination effects than dose addition, and where at the same time independent action also produced accurate predictions. The use of independent action as an assessment concept for combination effects requires demonstration that modes of action of individual substances in a mixture are strictly independent, a condition that can rarely be met in practice. The PPR Panel also noted that there is no cumulative risk assessment method derived from independent action. The PPR Panel therefore recommends using cumulative risk assessment methods derived from dose addition also for the assessment of mixtures of pesticides with dissimilar modes of action, provided they produce a common adverse outcome. Pesticides that produce common adverse outcomes on the same target organ/system should be grouped together in CAGs, and their combined effects assessed by using the concept of dose addition as a pragmatic and conservative default approach for the purpose of assessing cumulative risk in relation to MRL setting or risk assessment of chemical mixtures in practice.

The European Food Safety Authority asked the Panel on Plant Protection Products and their Residues to develop an Opinion on the identification of pesticides to be included in cumulative assessment groups (CAGs) on the basis of their toxicological profile. In 2008, the PPR Panel adopted an Opinion on the suitability of existing methodologies for cumulative risk assessment of pesticides and a tiered approach was proposed, which was applied to a selected group of triazole pesticides in 2009. The present Opinion suggests a methodology for grouping of pesticides based on phenomenological effects and provides CAGs for the thyroid and nervous system. This approach can be applied even when the underlying biochemical events mediating the effects are not understood, and is based on a standardised and thorough review of Draft Assessment Reports (DARs) supporting the approval of all pesticides in Europe, and on recommendations from the European Commission. Pesticidal active substances exhibiting neurotoxic properties were allocated to CAGs for acute effects on motor, sensory and autonomic divisions of the nervous system and neurochemical endpoints. Chronic effects across the same divisions/endpoints and neuropathological effects were collated. Active substances having adverse effects on the thyroid system were allocated to CAGs for effects either on C-cells/the calcitonin system or on follicular cells/the T3/T4 system. The PPR Panel notes that the resulting groups encompass many pesticides and also that individual pesticides could appear in several groups and therefore the data entries for performing cumulative risk assessment (CRA) are of considerable magnitude. Although some CAGs contain a large number of pesticides, little indication of cumulative risk may be inferred from the size of CAGs per se. The PPR Panel recommends that the methodology is implemented for all major organ/systems but the approach used should be considered specific for pesticides.

The European Food Safety Authority asked the Panel on Plant Protection Products (PPR) and their residues to deliver a Scientific Opinion on the developmental neurotoxicity (DNT) potential of the neonicotinoid insecticides acetamiprid and imidacloprid. An in vitro study (Kimura-Kuroda et al., 2012) suggested that excitation and/or desensitisation of nicotinic acetylcholine receptors (nAChRs) by these compounds might affect developing mammalian nervous systems as occurs with nicotine. To evaluate the DNT potential of acetamiprid and imidacloprid, the PPR Panel scrutinised the open literature, the draft assessments reports and dossiers submitted for approval. The Panel concludes that both compounds may affect neuronal development and function, although several methodological limitations have been identified. Considering the available DNT studies for imidacloprid and acetamiprid, important uncertainties still remain and further in vivo studies following OECD test guideline (TG) 426 are required to robustly characterise a DNT potential and dose-response relationships, particularly for acetamiprid. The Panel considers that current ARfDs may not be protective enough for the possible DNT of acetamiprid and imidacloprid and no reliable conclusion can be drawn as regards the ADI for acetamiprid. More conservative reference values are proposed based on the analysis of the existing toxicological data. However, the current ADI for imidacloprid is considered adequate to protect against its potential developmental neurotoxic effects. Limitations of the in vitro system used by Kimura-Kuroda et al. (2012) prevent its current use as a screening tool in the regulatory arena. The PPR Panel encourages the definition of clear and consistent criteria at EU level to trigger submission of mandatory DNT studies, which could include development of an integrated DNT testing strategy composed of robust, reliable and validated in vitro assays and other alternative methods complementary to the in vivo TG 426 for assessing the DNT potential of substances.

EFSA's Panel on Plant Protection Products and their Residues (PPR) was tasked to revise the Guidance Document (GD) on Aquatic Ecotoxicology under Council Directive 91/414/EEC (SANCO/3268/2001 rev.4 (final), 17 October 2002). This Guidance of the PPR Panel is the first of three requested deliverables within this mandate. It has its focus on tiered acute and chronic effect assessment schemes with detailed guidance on tier 1 and higher tier effect assessments for aquatic organisms in edge-of-field surface waters and on proposals regarding how to link effects to exposure estimates. The exposure assessment methodology was not reviewed and it is assumed that the current FOCUS surface water exposure assessment methodology will continue to be used for exposure assessment at EU level. The current GD is intended to be used for authorisation of active substances at EU level as well as for plant protection products at Member State level. The effect assessment schemes in this GD allow for the derivation of regulatory acceptable concentrations (RACs) on the basis of two options: (1) the ecological threshold option (ETO), accepting negligible population effects only, and (2) the ecological recovery option (ERO), accepting some population-level effects if ecological recovery takes place within an acceptable time period. In the tiered effect assessment schemes, in principle, all tiers (1, 2 and 3) are able to address the ETO, while the model ecosystem approach (tier 3), under certain conditions, is able to also address the ERO. The GD provides the scientific background for the risk assessment to aquatic organisms in edge-of-field surface waters and is structured to give detailed guidance on all assessment steps. An executive summary joining all parts of the guidance and decision schemes in a concise way is provided and is intended to help applicants and regulatory authorities in day-to-day use.

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