Population models are now recognized as useful tools to solve the issue of extrapolating toxicological effects measured at the organism level to potential impacts on populations. Nevertheless, the environmental realism of models employed in predictive approaches could be improved in order to yield a more pertinent risk assessment taking into account variability in population vulnerability and applicable with native species. Morevover, this could allow transferring the population extrapolation approach to the diagnostic framework. This work considers two phylogenetically and ecologically contrasted species (the Crustacean Amphipod Gammarus and the Mollusk Gastropod Potamopyrgus), widely present in European rivers and for which ecotoxicological (sub)individual biomarkers are available. First, we present how we developed environmentally realistic population models by using in situ caging methodologies. These Leslie models, which consider size-structured populations, link mechanistically individual-level demographic parameters (survival, growth, reproductive activity, fecundity, size at maturity) and the dynamics of reference native populations all along a year. Second, we illustrate with the case study of a wastewater treatment plant impact, how our modelling methodology coupled with in situ water quality biotests can propose population level assessment of water quality, and how the mechanistic analysis of population indicators sensibility could help to improve assessment of potential contamination impacts on ecologically relevant biological levels.