This chapter will start from the end of Chapter 2. Here we will advance and describe the improvements and adaptations of integrated methods based on weight-of-evidence (WoE) approaches used to address the impact and adverse effects of CO2 acidification in aquatic environments. Different set of data (already published or not) will be used to model and integrate the cause of the pollution (increase of CO2, increase of protons, changes in chemical equilibrium, etc.) with the consequence, the biological adverse effect (toxicity set of data obtained under laboratory conditions, adverse effects measured under in situ conditions, mesocosms, etc.). The main objective is to describe how this kind of integrative approach is capable to distinguish the cause related to the adverse effects measured in the aquatic ecosystem: (a) increase in the concentration of protons, (b) increase in the pCO2, (c) changes in the chemical equilibrium increasing the bioavailability of existing contaminants not associated with adverse effects till the CO2 acidification impact, and (d) mixture of the mentioned processes above. © 2022 Elsevier Inc. All rights reserved.