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

Abstract 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 The Panel noted that the draft guidance could only be used by experienced users because there is no software tool that fully supports the work flow in the guidance document.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

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia

In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP’s informed Integrated Approach for Testing and Assessment (IATA)

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Non-target terrestrial arthropods in prospective environmental risk assessment for plant protection products : Specific protection goal options

In 2015 the PPR Panel of the European Food Safety Authority (EFSA) published a scientific opinion on the state of the science on environmental risk assessment (ERA) for plant protection products and non- target terrestrial arthropods (EFSA PPR, 2015). An EFSA guidance document for prospective ERA of non- target terrestrial arthropods has not yet been developed since specific protection goals (SPGs) have to be defined in concert between risk assessors and risk managers and finally approved by EU risk managers. In this document, the prospective risk assessment procedures for pesticides and non-target terrestrial arthropods as currently used in the EU and in The Netherlands are described. In addition, a short overview of the recommendations in the EFSA scientific opinion on non-target terrestrial arthropods is given. Finally, four specific protection goal options for regulatory ERA for pesticides and non-target terrestrial arthropods are proposed. These options serve to facilitate discussions between risk assessors and risk managers and hopefully are helpful to risk managers in selecting the specific protection goal(s) that could form the basis for developing new EFSA/EU Member State guidance on tiered risk assessment for plant protection products and non-target terrestrial arthropods. The current report has its focus on the environmental/ecological consequences of the specific protection goal options. Evaluation of the agronomic consequences of the proposed specific protection goal options needs further elaboration and research

Supporting the development of exposure assessment scenarios for Non‐Target Terrestrial Organisms to plant protection products : Development of Exposure Assessment Goals

EU Regulation 1107/2009 requires the risk assessment of several groups of non-target organism (NTOs). To operationalize the rather generally defined protection goals in sectorial legislation, the concept of Specific Protection Goals (SPGs) has been developed. SPGs allow for an unambiguous definition of which ecosystem services need to be protected where and when. The evaluation of the SPGs is operationalised with the aid of Effect Assessment Goals (EfAG) and Exposure Assessment Goals (ExAG) that are assessed in a tiered approach, moving from simple and conservative lower tiers to more complex and more realistic higher tiers. The effect tiers specify ecotoxicological effects (observed for the imposed exposure in the ecotoxicological laboratory or (semi-) field experiments) while the exposure tiers result in the exposure measured or simulated in the field. They are linked by the so-called Ecotoxicologically Relevant Exposure Quantity, i.e. the type of exposure quantity that gives the best correlation to the observed ecotoxicological effect.This document describes the relatively new concept of EfAG into detail, highlighting the importance of well defining the surrogate reference tier, that represents the highest, experimentally feasible tier of the effect assessment. The in regulatory science well known ExAGs have been defined for (small) mammals off-field and Non Target Arthropods (NTAs) for one of the SPG options for NTAs, and may serve as an example for future guidance documents in this area.In view of the evaluation of the SPGs that are currently defined for in-field and off-field situations, it is demonstrated that the area around the cropped treated field needs to be defined more precisely. Currently, the terms ‘in-field’ and ‘off-field’ are not sufficiently specific. This difference is important with respect to the estimation of spray drift deposition (often the main exposure route), which is based upon the distance to the last row of crop. Depending on the local setting, this distance can be similar or very different between an in-field uncropped strip and off-field. Such differences are not reflected adequately using the current distinction for ‘in-field’ and ‘off-field’. Therefore, we propose to introduce the terms of ‘in-crop in-field’, ‘off-crop in-field’, and ‘off-crop off-field’

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

Abstract 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

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)

Abstract 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

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

Abstract 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