Nanomaterials are acclaimed for their novel properties, for which broad new uses are being discovered with increasing frequency. It is obvious that, as the properties change, unwanted properties (toxicity) are to be expected as well. Current toxicology, however, is already overwhelmed with the challenge of addressing new chemicals, not to mention the enormous number of old chemicals never properly assessed. Limitations of traditional approaches range from animal welfare issues, which were a strong driving force for alternative approaches (the 3Rs concept) over the last two decades, to aspects of throughput and accuracy of the predicted toxicities. The latter has prompted discussion about a revolutionary change in chemical safety assessment, now known as Toxicology for the 21st Century (Tox-21c). The multitude of possible formulations of nanomaterials to be assessed for novel toxic properties makes these alternative approaches especially attractive, given the well recognized limitations of traditional animal-based approaches--limitations that might be even more pronounced for nanomaterials, which have notably altered biokinetics.