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In the framework of the periodic update of the Sardinian River Basin Management and Water Protection Plans (Italian Law 152/2006, transposition of the 2000/60/EC Directive), we investigated the AQUATOX model feasibility as a tool for assessing the relationships between Driving forces, Pressures, States, Impacts and Responses (DPSIR scheme). To do this, we applied the AQUATOX model to forecast the response of a Sardinian (Italy) river quality status to a set of different environmental perturbations, including nutrient load and water flow variations. The final aim of this work is to study a feasible model, based on a DPSIR scheme, for identifying the necessary and sustainable measures to tackle the criticalities resulting from a set of known environmental perturbations on Sardinian rivers.