Bridging planarian bioassays and AOP-based environmental assessment: Toward mechanistic insights into pollutant-induced disruptions

Human activities have introduced a wide range of contaminants into aquatic ecosystems, posing substantial ecological and health risks. Robust bioindicators are essential for accurately predicting these impacts. Since the early 1980s, planarians—freshwater flatworms known for their remarkable regenerative ability and neurologically relevant system—have been used in ecotoxicology, witnessing renewed scientific interest post-2010. This critical review synthesizes and evaluates two decades of research on planarian toxicology, emphasizing behavioral and developmental endpoints upon exposure to metals, pharmaceuticals, pesticides, chemicals, nanomaterials, and biomaterials. Using an ecotoxicological Adverse Outcome Pathway (AOP) framework, we examine toxic mechanisms at the molecular, cellular, tissue/organ, organismal, and population-level. We also highlight recent advances in single-cell omics, metabolomics, and machine learning, and discuss their integration with automated high-throughput screening platforms to improve the predictive capacity of toxicological assessments. These approaches offer opportunities to address complex mixture toxicity and to better link laboratory findings with ecological effects. By combining multi-level biological organization with advanced analytical tools in an ecotoxicological AOP framework, this review provides a novel perspective that bridges classical toxicology with predictive environmental risk assessment, offering clear priorities for methodological standardization and expanded application in environmental monitoring.