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The toxicological effects of nanoparticles mixtures in aquatic organisms are poorly understood. The purpose of this study was to examine the tissue metal loadings and sublethal effects of silver (nAg), cerium oxide (nCeO), copper oxide (nCuO) and zinc oxide (nZnO) nanoparticles individually at 50 &micro, g/L and in two mixtures to freshwater mussels Dreissena bugensis. The mixtures consisted of 12.5 &micro, g/L of each nanoparticle (Mix50) and 50 &micro, g/L of each nanoparticles (Mix200). After a 96-h exposure period, mussels were analyzed for morphological changes, air time survival, bioaccumulation, inflammation (cyclooxygenase or COX activity), lipid peroxidation (LPO), DNA strand breaks, labile Zn, acetylcholinesterase (AChE) and protein&ndash, ubiquitin levels. The data revealed that mussels accumulated the nanoparticles with nCeO and nAg were the least and most bioavailable, respectively. Increased tissue metal loadings were observed for nCeO and nCuO in mixtures, while no mixture effects were observed for nAg and nZnO. The weight loss during air emersion was lower in mussels exposed to nCuO alone but not by the mixture. On the one hand, labile Zn levels was increased with nZnO but returned to control values with the Mix50 and Mix200, suggesting antagonism. On the other hand, DNA strand breaks were reduced for both mixtures compared to controls or to the nanoparticles individually, suggesting potentiation of effects. The same was found for protein&ndash, ubiquitin levels, which were decreased by nCeO and nCuO alone but not when in mixtures, which increased their levels. In conclusion, the data revealed that the behavior and effects of nanoparticles were influenced by other nanoparticles where antagonist and potentiation interactions were identified.