Nanomaterials (NMs) are a class of materials with at least one dimension in nanoscale that their application and production has increased over the past decades. Subsequently, the presence of NMs in the environments is steadily increasing, leading to questions over the potential influence they present to ecosystems. In the context of water monitoring and risk assessment, traditional ‘spot’ or ‘grab’ sampling approaches are increasingly supplemented by effect-based methods, which, however, may overlook important factors such as biota. A potential solution lies in integrating modern approaches, such as those employed in predictive ecotoxicology and adverse outcome pathway (AOP) frameworks, which utilize model species like Daphnia magna to assess the effects of nanomaterials and offer critical insights into their toxicity mechanisms and biological interactions. In this thesis, a holistic approach is employed by utilizing in vivo (daphnids) to better evaluate nanomaterial toxicity mechanisms as well as their impact on aquatic life. Silver nanoparticle impact was assessed using a range of phenotypic markers such as mortality, feeding rate, enzyme kinetics and metabolomics, which consistently showed significant impact on exposed individuals. Furthermore, significant findings were discovered in the context of the daphnia model experimental design, as well as metabolite coronas of silver nanoparticles that could improve and optimize toxicity testing for nanomaterials. Specifically, the feasibility of a miniaturized daphnia setup, as well as the importance of vessel geometry, animal crowding and nanocorona presence are discussed in their respective chapters.