TiO ₂ -ZnO Nanomaterial Interactions: Emerging Evidence of Co-Exposure Toxicity and Safety Implications

Titanium dioxide (TiO 2 ) and zinc oxide (ZnO) nanoparticles are some of the most common metal oxide nanoparticles in cosmetics, sunscreens, biomedical products and environmental applications. They commonly occur together and have the potential for co-occurrence, but there is limited understanding about the toxicological effects of their combination. In recent studies, it has been demonstrated that the physicochemical behavior of nanoparticles may be changed by interaction with TiO 2 and ZnO nanoparticles, including heteroaggregation, surface complexation and the adsorption of Zn 2+ ions, which can affect their biological activity and toxicity. Emerging evidence from experimental, environmental, and human-relevant studies indicates that co-exposure may induce enhanced oxidative stress, genotoxicity, reproductive dysfunction, and organ-specific damage compared with individual nanoparticle exposure. In some environmental settings, however, antagonistic effects are also reported, making the interaction of nanoparticles mixtures complex. The present review critically explores the existing knowledge about the interaction between TiO 2 and ZnO nanomaterials and implications for combined toxicity. Specific focus is given to the physicochemical mechanisms affecting the behavior of nanoparticles, the biological pathway involved in adverse outcomes, and a review of the limited but increasing evidence from co-exposure studies. There are also key research gaps, such as the lack of chronic exposure investigations, limited human data and the need for standardized approaches to the assessment of nanomaterial mixtures, discussed. Taken together, the existing evidence highlights the importance of developing interaction-aware safety assessment strategies for the sustainable development and safe use of TiO 2 –ZnO nanomaterials.