Advancing Soil Risk Assessment: A Novel Earthworm Cocoon Test with a Complementary Toxicokinetic-Toxicodynamic Modeling Approach.

In the current European Union pesticide risk assessment for soil organisms, effect endpoints from laboratory studies (Tier 1) and field studies (higher-tier risk assessment) are compared with predicted environmental concentrations in soil, derived from the proposed use pattern. The simple but conservative initial Tier 1 risk assessment considers a range of worst-case assumptions. In contrast, the higher-tier assessment focuses on specific conditions tested in the corresponding field study. Effect modeling, such as toxicokinetic-toxicodynamic (TKTD) modeling, is considered a promising future tool to address uncertainties in soil risk assessment, such as extrapolation to different ecological, pedo-climatical, or agronomical situations, or to serve as an intermediate tier for potential refinement of the risk assessment. For the implementation of TKTD modeling in soil organism risk assessment, data on earthworm growth and reproduction over time are required, which are not provided by the standard Organisation for Economic Co-operation and Development (OECD) 222 laboratory test. The underlying study with carbendazim presents a new earthworm cocoon test design, based on the OECD 222 test, to provide the necessary data as input for TKTD modeling. This proposed test design involves destructive samplings at days 7, 14, 21, and 28, enabling the determination of growth, cocoon number, and the number of juveniles hatched per cocoon in 7-day intervals. The new cocoon test allowed the disentanglement of the toxic effect of carbendazim in earthworms: At the highest concentration prominent effects on growth and reproductive output were observed, and the number of cocoons was significantly reduced compared to control. The results highlighted different physiological modes of action: effect on growth via higher maintenance costs as a primary mode of action as well as a reduced number of cocoons (effect on reproduction) and a lower number of juveniles hatching from each cocoon (hazard during oogenesis) as a secondary mode of action. We provide an example of how this new test's data can be used to feed a dynamic energy budget theory-TKTD model of Eisenia fetida. We also validate it against the original OECD 222 test design, outlining its potential future use in soil risk assessment. Environ Toxicol Chem 2024;43:2377-2386. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

SolBeePopecotox: A Population Model for Pesticide Risk Assessments of Solitary Bees.

In agricultural landscapes, solitary bees occur in a large diversity of species and are important for crop and wildflower pollination. They are distinguished from honey bees and bumble bees by their solitary lifestyle as well as different nesting strategies, phenologies, and floral preferences. Their ecological traits and presence in agricultural landscapes imply potential exposure to pesticides and suggest a need to conduct ecological risk assessments for solitary bees. However, assessing risks to the large diversity of managed and wild bees across landscapes and regions poses a formidable challenge. Population models provide tools to estimate potential population-level effects of pesticide exposures, can support field study design and interpretation, and can be applied to expand study data to untested conditions. We present a population model for solitary bees, SolBeePopecotox, developed for use in the context of ecological risk assessments. The trait-based model extends a previous version with the explicit representation of exposures to pesticides from relevant routes. Effects are implemented in the model using a simplified toxicokinetic-toxicodynamic model, BeeGUTS (GUTS = generalized unified threshold model for survival), adapted specifically for bees. We evaluated the model with data from semifield studies conducted with the red mason bee, Osmia bicornis, in which bees were foraging in tunnels over control and insecticide-treated oilseed rape fields. We extended the simulations to capture hypothetical semifield studies with two soil-nesting species, Nomia melanderi and Eucera pruinosa, which are difficult to test in empirical studies. The model provides a versatile tool for higher-tier risk assessments, for instance, to estimate effects of potential exposures, expanding available study data to untested species, environmental conditions, or exposure scenarios. Environ Toxicol Chem 2024;00:1-17. © 2024 SETAC.

Comparing Sensitivity of Different Bee Species to Pesticides: A TKTD modeling approach.

Risk assessment for bees is mainly based on data for honey bees; however, risk assessment is intended to protect all bee species. This raises the question of whether data for honey bees are a good proxy for other bee species. This issue is not new and has resulted in several publications in which the sensitivity of bee species is compared based on the values of the 48-h median lethal dose (LD50) from acute test results. When this approach is used, observed differences in sensitivity may result both from differences in kinetics and from inherent differences in species sensitivity. In addition, the physiology of the bee, like its overall size, the size of the honey stomach (for acute oral tests), and the physical appearance (for acute contact tests) also influences the sensitivity of the bee. The recently introduced Toxicokinetic-Toxicodynamic (TKTD) model that was developed for the interpretation of honey bee tests (Bee General Uniform Threshold Model for Survival [BeeGUTS]) could integrate the results of acute oral tests, acute contact tests, and chronic tests within one consistent framework. We show that the BeeGUTS model can be calibrated and validated for other bee species and also that the honey bee is among the more sensitive bee species. In addition, we found that differences in sensitivity between species are smaller than previously published comparisons based on 48-h LD50 values. The time-dependency of the LD50 and the specifics of the bee physiology are the main causes of the wider variation found in the published literature. Environ Toxicol Chem 2024;43:1431-1441. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Evaluating and Explaining the Variability of Honey Bee Field Studies across Europe Using BEEHAVE.

To assess the effect of plant protection products on pollinator colonies, the higher tier of environmental risk assessment (ERA), for managed honey bee colonies and other pollinators, is in need of a mechanistic effect model. Such models are seen as a promising solution to the shortcomings, which empirical risk assessment can only overcome to a certain degree. A recent assessment of 40 models conducted by the European Food Safety Authority (EFSA) revealed that BEEHAVE is currently the only publicly available mechanistic honey bee model that has the potential to be accepted for ERA purposes. A concern in the use of this model is a lack of model validation against empirical data, spanning field studies conducted in different regions of Europe and covering the variability in colony and environmental conditions. We filled this gap with a BEEHAVE validation study against 66 control colonies of field studies conducted across Germany, Hungary, and the United Kingdom. Our study implements realistic initial colony size and landscape structure to consider foraging options. Overall, the temporal pattern of colony strength is predicted well. Some discrepancies between experimental data and prediction outcomes are explained by assumptions made for model parameterization. Complementary to the recent EFSA study using BEEHAVE, our validation covers a large variability in colony conditions and environmental impacts representing the Northern and Central European Regulatory Zones. Thus we believe that BEEHAVE can be used to serve the development of specific protection goals as well as the development of simulation scenarios for the European Regulatory Zone. Subsequently, the model can be applied as a standard tool for higher tier ERA of managed honey bees using the mechanistic ecotoxicological module for BEEHAVE, BEEHAVEecotox . Environ Toxicol Chem 2023;42:1839-1850. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

The BEEHAVEecotox Model-Integrating a Mechanistic Effect Module into the Honeybee Colony Model.

Mechanistic effect models are powerful tools for extrapolating from laboratory studies to field conditions. For bees, several good models are available that can simulate colony dynamics. Controlled and reliable experimental systems are also available to estimate the inherent toxicity of pesticides to individuals. However, there is currently no systematic and mechanistic way of linking the output of experimental ecotoxicological testing to bee models for bee risk assessment. We introduce an ecotoxicological module that mechanistically links exposure with the hazard profile of a pesticide for individual honeybees so that colony effects emerge. This mechanistic link allows the translation of results from standard laboratory studies to relevant parameters and processes for simulating bee colony dynamics. The module was integrated into the state-of-the-art honeybee model BEEHAVE. For the integration, BEEHAVE was adapted to mechanistically link the exposure and effects on different cohorts to colony dynamics. The BEEHAVEecotox model was tested against semifield (tunnel) studies, which were deemed the best study type to test whether BEEHAVEecotox predicted realistic effect sizes under controlled conditions. Two pesticides used as toxic standards were chosen for this validation to represent two different modes of action: acute mortality of foragers and chronic brood effects. The ecotoxicological module was able to predict effect sizes in the tunnel studies based on information from standard laboratory tests. In conclusion, the BEEHAVEecotox model is an excellent tool to be used for honeybee risk assessment, interpretation of field and semifield studies, and exploring the efficiency of different mitigation measures. The principles for exposure and effect modules are portable and could be used for any well-constructed honeybee model. Environ Toxicol Chem 2022;41:2870-2882. © 2022 Bayer AG & Sygenta, et al. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Integrating earthworm movement and life history through dynamic energy budgets.

Earthworms are considered ecosystem engineers and, as such, they are an integral part of the soil ecosystem. The movement of earthworms is significantly influenced by environmental factors such as temperature and soil properties. As movement may directly be linked to food ingestion, especially of endogeic species like Aporrectodea caliginosa, changes in those environmental factors also affect life history traits such as growth and reproduction. In our laboratory studies, earthworms showed a decrease in burrowing activity with decreasing moisture levels and, to some extent, the organic matter content. The burrowing activity of earthworms was also affected by temperature, for which the casts produced per earthworm was used as a proxy in laboratory experiments. We integrated changes in earthworm movement and life histories in response to temperature, soil organic matter content and the moisture level, as observed in our experiment and reported in the literature, through dynamic energy budget (DEB) modelling. The joint parametrization of a DEB model for A. caliginosa based on movement and life history data revealed that food ingestion via movement is an integral part of the earthworms' energy budgets. Our findings highlight the importance of soil properties to be considered in the model development for earthworms. Furthermore, by understanding and incorporating the effect of environmental factors on the physiology, this mechanistic approach can help assess the impact of environmental changes such as temperature rise or drought.

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.

Towards a spatiotemporally explicit toxicokinetic-toxicodynamic model for earthworm toxicity.

The aim of the environmental risk assessment of chemicals is the prevention of unacceptable adverse effects on the environment. Therefore, the risk assessment for in-soil organisms, such as earthworms, is based on two key elements: the exposure assessment and the effect assessment. In the current risk assessment scheme, these two elements are not linked. While for the exposure assessment, advanced exposure models can take the spatial and temporal scale of substances into account, the effect assessment in the lower tiers considers only a limited temporal and spatial variability. However, for soil organisms, such as earthworms, those scales play a significant role as species move through the soil in response to environmental factors. To overcome this gap, we propose a conceptual integration of pesticide exposure, ecology, and toxicological effects on earthworms using a modular modeling approach. An essential part of this modular approach is the environment module, which utilizes exposure models to provide spatially and temporally explicit information on environmental variables (e.g., temperature, moisture, organic matter content) and chemical concentrations. The behavior module uses this information and simulates the feeding and movement of different earthworm species using a trait-based approach. The resulting exposure can be processed by a toxicokinetic-toxicodynamic (TKTD) module. TKTD models are particularly suitable to make effect predictions for time-variable exposure situations as they include the processes of uptake, elimination, internal distribution, and biotransformation of chemicals and link the internal concentration to an effect at the organism level. The population module incorporates existing population models of different earthworm species. The modular approach is illustrated using a case study with an insecticide. Our results emphasize that using a modular model approach will facilitate the integration of exposure and effects and thus enhance the risk assessment of soil organisms.