* We thank the Co-Editor Mark Broadie and an anonymous referee for comments that led to substantial improvements in this paper.

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. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. As a third deliverable of this mandate, the PPR Panel is asked to develop a Scientific Opinion describing the state of the art of Toxicokinetic/Toxicodynamic (TKTD) models for aquatic organisms and prospective environmental risk assessment (ERA) for pesticides with the main focus on: (i) regulatory questions that can be addressed by TKTD modelling, (ii) available TKTD models for aquatic organisms, (iii) model parameters that need to be included and checked in evaluating the acceptability of regulatory relevant TKTD models, and (iv) selection of the species to be modelled.Chapter 2 presents the underlying concepts, terminology, application domains and complexity levels of three different classes of TKTD models intended to be used in risk assessment, viz., (i) the 'General Unified Threshold models of Survival' (GUTS), (ii) toxicity models derived from the Dynamic Energy Budget theory (DEBtox models), and (iii) models for primary producers. All ...

Summary 1.Monitoring of exposure to pesticides in many countries shows extensive exposure of predators to anticoagulant rodenticides, which are used to control rats. Many predators and scavengers are declining in numbers, and exposure to rodenticides might therefore be of importance in conservation biology. 2. Predators and scavengers of poisoned rats are at most risk of secondary poisoning. However, several predatory species of conservation concern rarely eat rats, implicating non-target small mammals as the major route of exposure. For the first time, this research investigated the importance of non-target small mammals as routes of exposure to rodenticide for predators and scavengers in the UK. 3. Exposure studies of non-target small mammals were carried out alongside routine rat control at five sites, around agricultural buildings ( n = 2) and feed hoppers for game birds ( n = 3). 4. Three non-target rodent species fed on rodenticide from bait boxes during routine rat control treatments. A large proportion (48·6%) of individuals in local populations ate the bait: woodmice Apodemus sylvaticus were most exposed, followed by bank voles Clethrionomys glareolus then field voles Microtus agrestis . 5. Local populations of non-target small mammals declined significantly following rodenticidal rat control but their relative proportions did not change significantly. Populations recovered partially after 3 months, depending on the time of the year relative to the breeding cycle. 6. Synthesis and applications. Our results clearly demonstrate that routine rat control reduced local populations of non-target small mammals. This may limit the food supply of some specialist predators. Most importantly, this demonstrates a significant route of exposure of predators and scavengers of small mammals to secondary poisoning. Rodenticides are applied on farms and game estates across the UK. Hence the results of this study are indicative of non-target rodenticide exposure nationally. Mitigation requires a shift from the current reliance on rodenticides to ecologically based rodent management, involving improvements in site management and the adoption of good farming practice.

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Citation for published item:oppingD ghris tF nd grigD eter F nd de tongD prnk nd uleinD wihel nd vskowskiD yszrd nd wnhiniD frr nd ieperD ilvi nd mithD o nd ousD tos¡ e ulo nd treisslD prnz nd wrowskyD ulus nd iktkD eldrik nd vn der vindenD on @PHISA 9owrds lndspe sle mngement of pestiides X ie using hnges in modelled oupny nd undne to ssess longEterm popultion impts of pestiidesF9D iene of the totl environmentFD SQU F ppF ISWEITWF Further information on publisher's website: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractPesticides are regulated in Europe and this process includes an environmental risk assessment (ERA) for non-target arthropods (NTA). Traditionally a non-spatial or field trial assessment is used. In this study we exemplify the introduction of a spatial context to the ERA as well as suggest a way in which the results of complex models, necessary for proper inclusion of spatial aspects in the ERA, can be presented and evaluated easily using abundance and occupancy ratios (AOR). We used an agent-based simulation system and an existing model for a widespread carabid beetle (Bembidion lampros), to evaluate the impact of a fictitious highly-toxic pesticide on population density and the distribution of beetles in time and space. Landscape structure and field margin management were evaluated by comparing scenario-based ERAs for the beetle. Source-sink dynamics led to an off-crop impact even when no pesticide was present off-crop. In addition, the impacts increased with multi-year application of the pesticide whereas current ERA considers only maximally one year. These results further indicated a complex interaction between landscape structure and pesticide effect in time, both in-crop and off-crop, indicating the need for NTA ERA to be conducted at landscape-and multi-season temporal-scales. Use of AOR indices to compare ERA outputs facilitated easy comparison of scenarios, allowing simultaneous evaluation of impacts and planning of mitigation measures. The landscape and population ERA approach also demonstrates that there is a potential to change from regulation of a pesticide in isolation, towards the consideration of pesticide management at landscape scales and provision of biodiversity benefits via inclusion and testing of mitigation measures in authorisation procedures.

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Summary 1.Norway rat Rattus norvegicus populations are usually controlled with toxic baits, but this approach is increasingly recognized as having negative welfare and environmental impacts. An integrated strategy that relies less on rodenticides is therefore required. Here we investigate the possibility of using a resource-based approach to rat population management. 2. Structurally complex habitats provide rat populations with nest sites and opportunities to avoid predators; modifying habitats to reduce structural complexity might reduce their potential to support rat populations. As part of an integrated approach, this could be more sustainable than relying exclusively on lethal control. However, in order to target habitat management efforts most effectively with minimum impact on other species, an understanding of habitat utilization by Norway rats is required. 3. In this study, rat populations on farms in the north-east of England were monitored by radiotracking and population counts before and after a single phase of habitat modification. Rats living near farm buildings utilized areas with high levels of cover; habitat modification reduced the survival rate and size of these rat populations. Rats living in field margins also preferred areas with high levels of cover, but they had significantly bigger home ranges than rats living near farm buildings and were largely unaffected by small-scale habitat management. 4. Synthesis and applications . Our results indicate that habitat management near farm buildings has the potential to reduce the size of rat populations. As part of an integrated approach, this technique offers a way of reducing reliance on rodenticides. Habitat use by rats within the wider farm landscape suggests that land management practices have the potential to influence the size and distribution of rat populations; many game-rearing practices and environmental policies designed to create habitats for 'desirable' farm wildlife, inadvertently create desirable habitats for rats.