Functional toxicology of emerging contaminants: translating zebrafish models to ecological risk prediction

Zebrafish (Danio rerio) serve as a foundational mechanistic platform for investigating the toxicity of contaminants of emerging concern (CECs), including nanomaterials, rare earth elements, micro/nanoplastics, per- and polyfluoroalkyl substances (PFAS), and pharmaceuticals and personal care products (PPCPs). As a model organism, zebrafish offer unparalleled potential to elucidate complex biological processes ranging from toxicokinetics and organ-scale development to neurotoxicity and transgenerational effects. Such data facilitate the identification of effect pathways and biomarkers essential for environmental monitoring, risk assessment, and the development of intervention strategies. Equally vital is a thorough understanding of zebrafish genetics, physiology, and inherent limitations, which collectively dictate the accuracy of causal inferences. Despite their importance, these factors are rarely discussed in the context of ecological relevance, cross-species extrapolation, or their applicability to real-world risk predictions. In this perspective, I synthesize the current state of zebrafish functional toxicology and highlight recent technological advances for assessing CECs. I discuss the limitations and methodological considerations of the zebrafish model and propose a strategic path forward that integrates functional characterization and systems toxicology with ecological validation to bridge the gap between laboratory molecular perturbations and real-world regulatory risk assessment.