Statement of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on the design and conduct of groundwater monitoring studies supporting groundwater exposure assessments of pesticides.

Groundwater monitoring is the highest tier in the leaching assessment of plant protection products in the EU. The European Commission requested EFSA for a review by the PPR Panel of the scientific paper of Gimsing et al. (2019) on the design and conduct of groundwater monitoring studies. The Panel concludes that this paper provides many recommendations; however, specific guidance on how to design, conduct and evaluate groundwater monitoring studies for regulatory purposes is missing. The Panel notes that there is no agreed specific protection goal (SPG) at EU level. Also, the SPG has not yet been operationalised in an agreed exposure assessment goal (ExAG). The ExAG describes which groundwater needs to be protected, where and when. Because the design and interpretation of monitoring studies depends on the ExAG, development of harmonised guidance is not yet possible. The development of an agreed ExAG must therefore be given priority. A central question in the design and interpretation of groundwater monitoring studies is that of groundwater vulnerability. Applicants must demonstrate that the selected monitoring sites represent realistic worst-case conditions as specified in the ExAG. Guidance and models are needed to support this step. A prerequisite for the regulatory use of monitoring data is the availability of complete data on the use history of the products containing the respective active substances. Applicants must further demonstrate that monitoring wells are hydrologically connected to the fields where the active substance has been applied. Modelling in combination with (pseudo)tracer experiments would be the preferred option. The Panel concludes that well-conducted monitoring studies provide more realistic exposure assessments and can therefore overrule results from lower tier studies. Groundwater monitoring studies involve a high workload for both regulators and applicants. Standardised procedures and monitoring networks could help to reduce this workload.

Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.

Development of adverse outcome pathways (AOPs) for uterine adenocarcinoma can provide a practical tool to implement the EFSA-ECHA Guidance (2018) for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. AOPs can give indications about the strength of the relationship between an adverse outcome (intended as a human health outcome) and chemicals (pesticides but not only) affecting the pathways. In this scientific opinion, the PPR Panel explored the development of AOPs for uterine adenocarcinoma. An evidence-based approach methodology was applied, and literature reviews were produced using a structured framework assuring transparency, objectivity, and comprehensiveness. Several AOPs were developed; these converged to a common critical node, that is increased estradiol availability in the uterus followed by estrogen receptor activation in the endometrium; therefore, a putative AOP network was considered. An uncertainty analysis and a probabilistic quantification of the weight of evidence have been carried out via expert knowledge elicitation for each set of MIEs/KEs/KERs included in individual AOPs. The collected data on the AOP network were evaluated qualitatively, whereas a quantitative uncertainty analysis for weight of the AOP network certainty has not been performed. Recommendations are provided, including exploring further the uncertainties identified in the AOPs and putative AOP network; further methodological developments for quantifying the certainty of the KERs and of the overall AOPs and AOP network; and investigating of NAMs applications in the context of some of the MIEs/KEs currently part of the putative AOP network developed.

Statement on the active substance flupyradifurone.

Flupyradifurone is a novel butenolide insecticide, first approved as an active substance for use in plant protection products by Commission Implementing Regulation (EU) 2015/2084. Following concerns that this substance may pose high risks to humans and the environment, the French authorities, in November 2020, asked the Commission to restrict its uses under Article 69 of Regulation (EC) No 1107/2009. To support this request, competent Authorities from France cited a series of literature papers investigating its hazards and/or exposure to humans and the environment. In addition, in June 2020, the Dutch Authorities notified the Commission, under Article 56 of Regulation (EC) No 1107/2009, of new information on flupyradifurone on the wild bee species Megachile rotundata. This notification is also referred to in the French notification on flupyradifurone. Consequently, the EFSA PPR Panel was mandated to quantify the likelihood of this body of evidence constituting proof of serious risks to humans or the environment. Therefore, the EFSA PPR Panel evaluated the likelihood of these studies indicating new or higher hazards and exposure to humans and the environment compared to previous EU assessments. A stepwise methodology was designed, including: (i) the initial screening; (ii) data extraction and critical appraisal based on the principles of OHAT/NTP; (iii) weight of evidence, including consideration of the previous EU assessments; (iv) uncertainty analysis, followed, whenever relevant, by an expert knowledge elicitation process. For the human health, only one study was considered relevant for the genotoxic potential of flupyradifurone in vitro. These data did not provide sufficient information to overrule the EU assessment, as in vivo studies already addressed the genotoxic potential of flupyradifurone. Environment: All available data investigated hazards in bee species. For honey bees, the likelihood of the new data indicating higher hazards than the previous EU assessment was considered low or moderate, with some uncertainties. However, among solitary bee species - which were not addressed in the previous EU assessment - there was evidence that Megachile rotundata may be disproportionately sensitive to flupyradifurone. This sensitivity, which may partially be explained by the low bodyweight of this species, was mechanistically linked to inadequate bodily metabolisation processes.

Statement on the active substance acetamiprid.

Acetamiprid is a pesticide active substance with insecticidal action currently under the third renewal (AIR3) of the Commission implementing regulation (EU) No 844/2012. Following concerns that this substance may pose high risks to humans and the environment, the French authorities asked the Commission to restrict its uses under Article 69 of Regulation (EC) No 1107/2009. To support this request, competent Authorities from France cited a series of literature papers investigating its hazards and/or exposure to humans and the environment. Consequently, the EFSA PPR Panel was mandated to advise on the likelihood that body of evidence would constitute proof of serious risks to humans or the environment. Therefore, the EFSA PPR Panel evaluated the likelihood of these studies indicating new or higher hazards and exposure to humans and the environment compared to previous EU assessments.A stepwise methodology was designed, including: (i) the initial screening; (ii) the data extraction and critical appraisal based on the principles of OHAT/NTP; (iii) the weight of evidence, including consideration of the previous EU assessments; (iv) the uncertainty analysis, followed, whenever relevant, by an expert knowledge elicitation process. For human health, no conclusive evidence of higher hazards compared to previous assessment was found for genotoxicity, developmental toxicity, neurotoxicity including developmental neurotoxicity and immunotoxicity. However, due to the lack of adequate assessment of the current data set, the PPR Panel recommends conducting an assessment of endocrine disrupting properties for acetamiprid in line with EFSA/ECHA guidance document for the identification of endocrine disruptors. For environment, no conclusive, robust evidence of higher hazards compared to the previous assessment was found for birds, aquatic organisms, bees and soil organisms. However, the potential of high inter-species sensitivity of birds and bees towards acetamiprid requires further consideration.

Statement of the PPR Panel on a framework for conducting the environmental exposure and risk assessment for transition metals when used as active substances in plant protection products (PPP).

The European Commission asked the European Food Safety Authority (EFSA) to prepare a statement on a framework for the environmental risk assessment (ERA) of transition metals (e.g. iron and copper) used as active substances in plant protection products (PPPs). Non-degradability, essentiality and specific conditions affecting fate and behaviour as well as their toxicity are distinctive characteristics possibly not covered in current guidance for PPPs. The proposed risk assessment framework starts with a preliminary phase, in which monitoring data on transition metals in relevant environmental compartments are provided. They deliver the metal natural background and anthropogenic residue levels to be considered in the exposure calculations. A first assessment step is then performed assuming fully bioavailable residues. Should the first step fail, refined ERA can, in principle, consider bioavailability issues; however, non-equilibrium conditions need to be taken into account. Simple models that are fit for purpose should be employed in order to avoid unnecessary complexity. Exposure models and scenarios would need to be adapted to address environmental processes and parameters relevant to the fate and behaviour of transition metals in water, sediment and soils (e.g. speciation). All developments should follow current EFSA guidance documents. If refined approaches have been used in the risk assessment of PPPs containing metals, post-registration monitoring and controlled long-term studies should be conducted and assessed. Utilisation of the same transition metal in other PPPs or for other uses will lead to accumulation in environmental compartments acting as sinks. In general, it has to be considered that the prospective risk assessment of metal-containing PPPs can only cover a defined period as there are limitations in the long-term hazard assessment due to issues of non-degradability. It is therefore recommended to consider these aspects in any risk management decisions and to align the ERA with the goals of other overarching legislative frameworks.

The Role of Behavioral Ecotoxicology in Environmental Protection.

For decades, we have known that chemicals affect human and wildlife behavior. Moreover, due to recent technological and computational advances, scientists are now increasingly aware that a wide variety of contaminants and other environmental stressors adversely affect organismal behavior and subsequent ecological outcomes in terrestrial and aquatic ecosystems. There is also a groundswell of concern that regulatory ecotoxicology does not adequately consider behavior, primarily due to a lack of standardized toxicity methods. This has, in turn, led to the exclusion of many behavioral ecotoxicology studies from chemical risk assessments. To improve understanding of the challenges and opportunities for behavioral ecotoxicology within regulatory toxicology/risk assessment, a unique workshop with international representatives from the fields of behavioral ecology, ecotoxicology, regulatory (eco)toxicology, neurotoxicology, test standardization, and risk assessment resulted in the formation of consensus perspectives and recommendations, which promise to serve as a roadmap to advance interfaces among the basic and translational sciences, and regulatory practices.

Application of General Unified Threshold Models of Survival Models for Regulatory Aquatic Pesticide Risk Assessment Illustrated with an Example for the Insecticide Chlorpyrifos.

Mathematical models within the General Unified Threshold models of Survival (GUTS) framework translate time-variable chemical exposure information into expected survival of animals. The GUTS models are species and compound specific and explicitly describe the internal exposure dynamics in an organism (toxicokinetics) and the related damage and effect dynamics (toxicodynamics), thereby connecting the external exposure concentration dynamics with the simulated mortality or immobility over time. In a recent scientific opinion on toxicokinetic-toxicodynamic (TKTD) models published by the European Food Safety Authority (EFSA), the GUTS modeling framework was considered ready for use in the aquatic risk assessment for pesticides and aquatic fauna. The GUTS models are suggested for use in risk assessment, if they are sufficiently validated for a specific substance-species combination. This paper aims to illustrate how they can be used in the regulatory environmental risk assessment for pesticides for a specific type of refinement, that is, when risks are triggered by lower tiers in acute as well as in chronic risk assessment and mortality or immobility is the critical endpoint. This approach involves the evaluation of time-variable exposure regimes in a so-called "Tier-2C" assessment. The insecticide chlorpyrifos was selected as an example compound because a large data set was available. The GUTS models for 13 different freshwater arthropods and 8 different theoretical aquatic exposure profiles were used to calculate a series of GUTS-based risk estimates, including exposure profile-specific multiplication factors leading to 50% mortality or immobility at the end of the tested profile (LP50/EP50) as "margins of safety." To put the use of GUTS models within the tiered aquatic risk assessment into perspective, GUTS models for the 13 aquatic arthropods were also used to predict the environmental risks of a measured chlorpyrifos exposure profile from an experimental ditch study (Tier-3 approach), and the results are discussed in the context of calibration of the tiered approach. Integr Environ Assess Manag 2021;17:243-258. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Mechanistic Effect Modeling of Earthworms in the Context of Pesticide Risk Assessment: Synthesis of the FORESEE Workshop.

Earthworms are important ecosystem engineers, and assessment of the risk of plant protection products toward them is part of the European environmental risk assessment (ERA). In the current ERA scheme, exposure and effects are represented simplistically and are not well integrated, resulting in uncertainty when the results are applied to ecosystems. Modeling offers a powerful tool to integrate the effects observed in lower tier laboratory studies with the environmental conditions under which exposure is expected in the field. This paper provides a summary of the (In)Field Organism Risk modEling by coupling Soil Exposure and Effect (FORESEE) Workshop held 28-30 January 2020 in Düsseldorf, Germany. This workshop focused on toxicokinetic-toxicodynamic (TKTD) and population modeling of earthworms in the context of ERA. The goal was to bring together scientists from different stakeholder groups to discuss the current state of soil invertebrate modeling and to explore how earthworm modeling could be applied to risk assessments, in particular how the different model outputs can be used in the tiered ERA approach. In support of these goals, the workshop aimed at addressing the requirements and concerns of the different stakeholder groups to support further model development. The modeling approach included 4 submodules to cover the most relevant processes for earthworm risk assessment: environment, behavior (feeding, vertical movement), TKTD, and population. Four workgroups examined different aspects of the model with relevance for risk assessment, earthworm ecology, uptake routes, and cross-species extrapolation and model testing. Here, we present the perspectives of each workgroup and highlight how the collaborative effort of participants from multidisciplinary backgrounds helped to establish common ground. In addition, we provide a list of recommendations for how earthworm TKTD modeling could address some of the uncertainties in current risk assessments for plant protection products. Integr Environ Assess Manag 2021;17:352-363. © 2020 SETAC.

Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative in vitro metabolism studies.

EFSA asked the Panel on Plant Protection Products and their residues to deliver a Scientific Opinion on testing and interpretation of comparative in vitro metabolism studies for both new active substances and existing ones. The main aim of comparative in vitro metabolism studies of pesticide active substances is to evaluate whether all significant metabolites formed in the human in vitro test system, as a surrogate of the in vivo situation, are also present at comparable level in animal species tested in toxicological studies and, therefore, if their potential toxicity has been appropriately covered by animal studies. The studies may also help to decide which animal model, with regard to a particular compound, is the most relevant for humans. In the experimental strategy, primary hepatocytes in suspension or culture are recommended since hepatocytes are considered the most representative in vitro system for prediction of in vivo metabolites. The experimental design of 3 × 3 × 3 (concentrations, time points, technical replicates, on pooled hepatocytes) will maximise the chance to identify unique (UHM) and disproportionate (DHM) human metabolites. When DHM and UHM are being assessed, test item-related radioactivity recovery and metabolite profile are the most important parameters. Subsequently, structural characterisation of the assigned metabolites is performed with appropriate analytical techniques. In toxicological assessment of metabolites, the uncertainty factor approach is the first alternative to testing option, followed by new approach methodologies (QSAR, read-across, in vitro methods), and only if these fail, in vivo animal toxicity studies may be performed. Knowledge of in vitro metabolites in human and animal hepatocytes would enable toxicological evaluation of all metabolites of concern, and, furthermore, add useful pieces of information for detection and evaluation of metabolites in different matrices (crops, livestock, environment), improve biomonitoring efforts via better toxicokinetic understanding, and ultimately, develop regulatory schemes employing physiologically based or physiology-mimicking in silico and/or in vitro test systems to anticipate the exposure of humans to potentially hazardous substances in plant protection products.

Statement on the translocation potential by Pseudomonas chlororaphis MA342 in plants after seed treatment of cereals and peas and assessment of the risk to humans.

The European Commission requested EFSA to provide scientific advice on the translocation potential by Pseudomonas chlororaphis MA342 in plants after seed treatment of cereals and peas and, if applicable, for a revision of the assessment of the risk to humans by its metabolite 2,3-deepoxy-2,3-didehydro-rhizoxin (DDR) and this based on the evidence available in the dossier for renewal of the approval. The information from other P. chlororaphis strains than MA342 was taken into account with care, because the studies available in the dossier did not confirm the identity of the strain MA342 as belonging to the species P. chlororaphis. It has been concluded that there is a potential for translocation of P. chlororaphis MA342 to edible plant parts following seed treatment till an estimated concentration up to about 105 cfu/g and some exposure can be assumed by consumption of fresh commodities. Also, production of the metabolite DDR in the plant cannot be excluded. Regarding levels of DDR in the raw agricultural commodities, exposure estimates based on the limit of quantification (LOQ) for DDR in cereals cannot be further refined while there is no information on the levels of DDR in peas in the dossier. As regards genotoxicity, DDR induced chromosomal damage; however, it was not possible to conclude whether it is through an aneugenic or clastogenic mechanism. Hence, it is not possible to draw a reliable conclusion that DDR is producing an aneugenic effect nor to determine a threshold dose for aneugenicity. Thus, it is not possible to revise the human risk assessment as regards exposure to DDR. The concerns identified in the EFSA conclusion of 2017 remain.

Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on the genotoxic potential of triazine amine (metabolite common to several sulfonylurea active substances).

The Panel received a mandate from the European Commission to assess the genotoxic potential of triazine amine based on available information submitted by the applicants. Available information includes experimental genotoxicity data on triazine amine, Quantitative Structure-Activity Relationship (QSAR) analysis and read across with structurally similar compounds. Based on the overall weight of evidence, the Panel, in agreement with the cross-cutting Working Group Genotoxicity, concluded that there is no concern for the potential of triazine amine to induce gene mutations and clastogenicity; however, the potential to induce aneugenicity was not adequately investigated. For a conclusion, an in vitro micronucleus assay performed with triazine amine would be needed.

Better define beta-optimizing MDD (minimum detectable difference) when interpreting treatment-related effects of pesticides in semi-field and field studies.

The minimum detectable difference (MDD) is a measure of the difference between the means of a treatment and the control that must exist to detect a statistically significant effect. It is a measure at a defined level of probability and a given variability of the data. It provides an indication for the robustness of statistically derived effect thresholds such as the lowest observed effect concentration (LOEC) and the no observed effect concentration (NOEC) when interpreting treatment-related effects on a population exposed to chemicals in semi-field studies (e.g., micro-/mesocosm studies) or field studies. MDD has been proposed in the guidance on tiered risk assessment for plant protection products in edge of field surface waters (EFSA Journal 11(7):3290, 2013), in order to better estimate the robustness of endpoints from such studies for taking regulatory decisions. However, the MDD calculation method as suggested in this framework does not clearly specify the power which is represented by the beta-value (i.e., the level of probability of type II error). This has implications for the interpretation of experimental results, i.e., the derivation of robust effect values and their use in risk assessment of PPPs. In this paper, different methods of MDD calculations are investigated, with an emphasis on their pre-defined levels of type II error-probability. Furthermore, a modification is suggested for an optimal use of the MDD, which ensures a high degree of certainty for decision-makers.

Scientific Opinion on the setting of health-based reference values for metabolites of the active substance terbuthylazine.

The EFSA Panel on Plant Protection Products and their Residues was requested to establish health-based reference values for groundwater metabolites (LM2, LM3, LM4, LM5 and LM6) of the active substance terbuthylazine based on the available evidence, unless the evidence was considered insufficient to do so. The request was accepted under the explicit circumstance that the reassessment would be made according to a different methodology than the routine methodology currently applied for the assessment of metabolites in groundwater. While for metabolites LM2, LM4 and LM5, it was concluded that the reference values for terbuthylazine are applicable, substance-specific reference values could not be derived for metabolites LM3 and LM6. The applied threshold of toxicological concern (TTC) approach has shown that metabolites LM3 and LM6 are of potential concern for consumer health, since at least one representative groundwater leaching scenario results in exposure above the relevant threshold. Moreover, other sources of exposure to LM3 and LM6 could not be excluded with certainty. It is therefore recommended to address the specific toxicities of metabolites LM3 and LM6.

Scientific statement on the coverage of bats by the current pesticide risk assessment for birds and mammals.

Bats are an important group of mammals, frequently foraging in farmland and potentially exposed to pesticides. This statement considers whether the current risk assessment performed for birds and ground dwelling mammals exposed to pesticides is also protective of bats. Three main issues were addressed. Firstly, whether bats are toxicologically more or less sensitive than the most sensitive birds and mammals. Secondly, whether oral exposure of bats to pesticides is greater or lower than in ground dwelling mammals and birds. Thirdly, whether there are other important exposure routes relevant to bats. A large variation in toxicological sensitivity and no relationship between sensitivity of bats and bird or mammal test-species to pesticides could be found. In addition, bats have unique traits, such as echolocation and torpor which can be adversely affected by exposure to pesticides and which are not covered by the endpoints currently selected for wild mammal risk assessment. The current exposure assessment methodology was used for oral exposure and adapted to bats using bat-specific parameters. For oral exposure, it was concluded that for most standard risk assessment scenarios the current approach did not cover exposure of bats to pesticide residues in food. Calculations of potential dermal exposure for bats foraging during spraying operations suggest that this may be a very important exposure route. Dermal routes of exposure should be combined with inhalation and oral exposure. Based on the evidence compiled, the Panel concludes that bats are not adequately covered by the current risk assessment approach, and that there is a need to develop a bat-specific risk assessment scheme. In general, there was scarcity of data to assess the risks for bat exposed to pesticides. Recommendations for research are made, including identification of alternatives to laboratory testing of bats to assess toxicological effects.

Controlling Culex pipiens: antagonists are more efficient than a neonicotinoid insecticide.

Species vulnerability to pesticides depends on physiological sensitivity, the potential to recover, and the ecological context. We assessed the vulnerability of the mosquito Culex pipiens to a repeated treatment with thiacloprid in outdoor microcosms with and without antagonists (competitive and predatory invertebrates). Microcosms were treated repeatedly (three times) with thiacloprid at a concentration of 0.1, 1, or 10 µg/liter. In microcosms without antagonists, the abundance of Cx. pipiens larvae decreased moderately after the second and the third exposures to 10 µg/liter thiacloprid. In microcosms with antagonists, the abundance of Cx. pipiens larvae declined to approximately zero in the control group and the low concentration treatments during the five weeks of observation. By contrast, the abundance of Cx. pipiens larvae temporarily increased at 10 µg/liter thiacloprid after the second and third contamination. We explained this positive effect on the development of Cx. pipiens because of the decrease in competition due to the elimination of sensitive antagonists combined with the high recovery potential of Cx. pipiens. Based on these results, natural antagonists must be supported for the sustainable control of mosquitoes.

Scientific Opinion on the state of the science on pesticide risk assessment for amphibians and reptiles.

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.

Scientific opinion on pesticides in foods for infants and young children.

Following a request from the European Commission, the EFSA Panel on Plant Protection Products and their Residues (PPR Panel) prepared a scientific opinion to provide a comprehensive evaluation of pesticide residues in foods for infants and young children. In its approach to develop this scientific opinion, the EFSA PPR Panel took into account, among the others, (i) the relevant opinions of the Scientific Committee for Food setting a default maximum residue level (MRL) of 0.01 mg/kg for pesticide residues in foods for infants and young children; (ii) the recommendations provided by EFSA Scientific Committee in a guidance on risk assessment of substances present in food intended for infants below 16 weeks of age; (iii) the knowledge on organ/system development in infants and young children. For infants below 16 weeks of age, the EFSA PPR Panel concluded that pesticide residues at the default MRL of 0.01 mg/kg for food for infants and young children are not likely to result in an unacceptable exposure for active substances for which a health-based guidance value (HBGV) of 0.0026 mg/kg body weight (bw) per day or higher applies. Lower MRLs are recommended for active substances with HBGVs below this value. For infants above 16 weeks of age and young children, the established approach for setting HBGVs is considered appropriate. For infants below 16 weeks of age the approach may not be appropriate and the application of the EFSA guidance on risk assessment of substances present in food intended for infants below 16 weeks of age is recommended. The contribution of conventional food to the total exposure to pesticide residues is much higher than that from foods intended for infants and young children. Because of the increased intake of conventional food by young children, these have the highest exposure to pesticide residues, whereas infants 3-6 months of age generally have lower exposure. The impact of cumulative exposure to pesticide residues on infants and young children is not different from the general population and the EFSA cumulative risk assessment methodology is also applicable to these age groups. Residue definitions established under Regulation (EC) No 396/2005 are in general considered appropriate also for foods for infants and young children. However, based on a tier 1 analysis of the hydrolysis potential of pesticides simulating processing, the particular appropriateness of existing residue definitions for monitoring to cover processed food, both intended for infants and young children as well as conventional food, is questionable.

Scientific Opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) effect models for regulatory risk assessment of pesticides for aquatic organisms.

Following a request from EFSA, the Panel on Plant Protection Products and their Residues (PPR) developed an opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) models and their use in prospective environmental risk assessment (ERA) for pesticides and aquatic organisms. TKTD models are species- and compound-specific and can be used to predict (sub)lethal effects of pesticides under untested (time-variable) exposure conditions. Three different types of TKTD models are described, viz., (i) the 'General Unified Threshold models of Survival' (GUTS), (ii) those based on the Dynamic Energy Budget theory (DEBtox models), and (iii) models for primary producers. All these TKTD models follow the principle that the processes influencing internal exposure of an organism, (TK), are separated from the processes that lead to damage and effects/mortality (TD). GUTS models can be used to predict survival rate under untested exposure conditions. DEBtox models explore the effects on growth and reproduction of toxicants over time, even over the entire life cycle. TKTD model for primary producers and pesticides have been developed for algae, Lemna and Myriophyllum. For all TKTD model calibration, both toxicity data on standard test species and/or additional species can be used. For validation, substance and species-specific data sets from independent refined-exposure experiments are required. Based on the current state of the art (e.g. lack of documented and evaluated examples), the DEBtox modelling approach is currently limited to research applications. However, its great potential for future use in prospective ERA for pesticides is recognised. The GUTS model and the Lemna model are considered ready to be used in risk assessment.

Scientific Opinion about the Guidance of the Chemical Regulation Directorate (UK) on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessments.

The EFSA Panel on Plant Protection Products and their Residues reviewed the guidance on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessment. The inclusion of aged sorption is a higher tier in the groundwater leaching assessment. The Panel based its review on a test with three substances taken from a data set provided by the European Crop Protection Association. Particular points of attention were the quality of the data provided, the proposed fitting procedure of aged sorption experiments and the proposed method for combining results obtained from aged sorption studies and lower-tier studies on degradation and adsorption. Aged sorption was a relevant process in all cases studied. The test revealed that the guidance could generally be well applied and resulted in robust and plausible results. The Panel considers the guidance suitable for use in the groundwater leaching assessment after the recommendations in this Scientific Opinion have been implemented, with the exception of the use of field data to derive aged sorption parameters. The Panel noted that the draft guidance could only be used by experienced users because there is no software tool that fully supports the work flow in the guidance document. It is therefore recommended that a user-friendly software tool be developed. Aged sorption lowered the predicted concentration in groundwater. However, because aged sorption experiments may be conducted in different soils than lower-tier degradation and adsorption experiments, it cannot be guaranteed that the higher tier predicts lower concentrations than the lower tier, while lower tiers should be more conservative than higher tiers. To mitigate this problem, the Panel recommends using all available higher- and lower-tier data in the leaching assessment. The Panel further recommends that aged sorption parameters for metabolites be derived only from metabolite-dosed studies. The formation fraction can be derived from parent-dosed degradation studies, provided that the parent and metabolite are fitted with the best-fit model, which is the double first-order in parallel model in the case of aged sorption.