Combined Modeling of Multiple Exposure Routes for Terrestrial Arthropods Using the Toxicokinetic–Toxicodynamic BufferGUTS Model

Pesticide applications in agricultural landscapes pose significant risks to nontarget arthropods (NTAs), which are vital for maintaining ecological functions such as pollination and pest control. Effective risk assessment is made challenging by the complexity of terrestrial exposure, which is highly variable and event-driven. Unlike in aquatic settings, NTAs experience pesticide exposure through multiple routes, such as overspray, ingestion, or contact. To integrate such multiple exposure routes into a unified framework, this study proposes an extension to the toxicokinetic-toxicodynamic (TKTD) and time-resolved BufferGUTS model that can be applied to a broad range of NTAs without species-specific adaptations. Our model extension draws on principles from mixture toxicity and allows for individual effect contributions and effect kinetics per uptake route, providing further insight into the substance effect dynamics. We tested the model using honeybee (Apis mellifera) data for topical and oral exposures to five insecticides. Among the insecticides tested, only one exhibited different kinetics between topical and oral applications, while three exhibited nonsimilar effects from the two routes. We recommend the integration of such TKTD models into environmental risk assessment practices to combine uptake route effects, model field-relevant exposure scenarios, and identify the most relevant routes for each substance. This will enable more informed decision-making, thereby enhancing ecological management and protection efforts.