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;00:1-10. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Physiological Dependency Explains Temperature Differences in Sensitivity Towards Chemical Exposure.

In chemical risk assessment, extrapolations from laboratory tests to more realistic conditions are essential to address the toxic effects of pesticides on individuals and populations under field conditions. To transfer toxicological laboratory tests to differing temperature conditions, or outdoor field scenarios, the consideration of temperature dependence is essential and increases realism. Special consideration is given to the impact of temperature on direct sensitivity of organisms to pesticides, for which there are only few modelling approaches available so far. We present a concept for applying physiological temperature dependencies to toxicokinetic-toxicodynamic (TKTD) parameters in the General Uniformed Threshold model of Survival (GUTS). To test this approach in an exemplary study, temperature dependencies from studies on the developmental rate of the mayfly Cloeon dipterum were applied to the parameters of a previously parameterised TKTD model of this species after exposure to imidacloprid. Using a physiologically derived temperature correction for the TKTD rate constants, model predictions for independently conducted toxicology experiments with temperature ranges between 7.8 and 26.4 °C were performed for validation. Our approach demonstrates the successful transfer of a physiological observed temperature dependency on toxicity parameters and survival patterns for Cloeon dipterum and imidacloprid as a case study.

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.

Mechanistic Effect Modeling Approach for the Extrapolation of Species Sensitivity.

In the higher-tier environmental risk assessment of chemicals, species sensitivity distributions (SSDs) are used to statistically describe differences in sensitivity between species and derive community level endpoints. SSDs are usually based on the results from short-term laboratory experiments performed under constant environmental conditions. However, different species may be kept at different "optimal" temperatures, which influence their apparent sensitivity and thus the derivation of endpoints. Also, the extrapolation capacity of SSDs is largely limited to the tested species and conditions. Time-variable exposures and effects at higher levels of biological organization, including biological interactions, are not considered. The quantitative effect prediction at higher tiers would ultimately require the extrapolation of toxicokinetics and toxicodynamics to untested species and the involvement of population and community modeling. In this regard, we tested a toxicokinetic-toxicodynamic modeling approach to mechanistically consider and correct endpoints for ambient temperature and demonstrate the significance for SSDs. We explored correlations in toxicokinetic-toxicodynamic model parameters which would allow for the extrapolation of sensitivities to untested species. Finally, we illustrate the applicability of the approach for higher level effect predictions using an individual-based model. Our results suggest that mechanistic effect modeling approaches can reduce the uncertainties in higher tier effect assessments related to knowledge gaps.