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Nanoparticles are used in many different applications because of their small size and unique properties. The usage is increasing rapidly, which will increase the nanoparticle exposure to the environment. Up till now, environmental behavior and ecotoxicology of nanoparticles have only been studied to a certain extent and because of the increasing usage, research should focus more on nanoparticle behavior and ecotoxicology. An effective way of studying nanoparticles in aqueous environments is to use mathematical models. In this study, the In vitro Sedimentation, Diffusion, and Dosimetry (ISDD) model was investigated and applied to copper, manganese, and zinc oxide nanoparticles to determine their sedimentation velocity in 1 mM NaClO4(aq). The results show that the simulated sedimentation of nanoparticles in solution, i.e. the output from the ISDD model, can vary a lot depending on some of the input parameters in the model. The fact that some of these parameters have to be estimated increases the uncertainty of the ISDD model, although it is possible to yield results in great agreement with experimentally determined sedimentation velocities for the studied systems. The simulation results could always be explained by the theory behind it, which increases the reliability of the ISDD model. The possibility of measuring the effective density of nanoparticle agglomerates using the volumetric centrifugation method was also investigated. This method makes it possible to avoid estimating the fractal dimension, an input parameter with great uncertainty in the ISDD model. The results look promising, although further investigation is needed. The ISDD model seems to be a promising model for future simulation work. The model should be investigated further in order to minimize the uncertainties due to estimations. The possibility to predict nanoparticle sedimentation using a mathematical model will save a lot of time and money, and it can be a helpful tool in the extensive work of identifying the behavior of nanoparticles in aqueous environments.