In vivo models are the most represetative, but due to 3Rs application, I recomend you to use in vitro models. According to your previous answer indicating that the routes are oral and respiratory, I recomend you to use intestinal model based on CaCo-2 cells cultured on transwells for absorption and toxicity. You can also co-culture them with endothelial cells and mimic the crossing towards the blood vessels. For inhalation toxicity, MucilAir model from Epitheliz Sarl (http://www.epithelix.com/content/view/6/5/) is a good alternative to in vivo testing.
there are many models that you could use for nanotoxicity assay, eg: zebrafish model, mussels, but don't forget to build your own objectives and what is your goal from this studies because you will find a very big debated discusses espeacially between toxicologists and medecin (scientists would apply nanotechnology in medecine).