This is a copy of the slides presented at the meeting but not formally written up for the volume.

Manipulation of the physicochemical properties of materials at the nanoscale has the potential to revolutionize electronic, diagnostic, and therapeutic applications. Because of the potential large-scale use of nanomaterials, it is important to determine if there is any unique toxicity of the nanoscale materials as compared to the bulk. It is essential for the purposes of interpreting results from cell culture and animal models that the nanomaterials are thoroughly characterized and that correlations are made between observed toxicological responses and the physicochemical characteristics of the materials. We hypothesize that nanomaterials by virtue of their size and surface activity can induce oxidative stress following exposures in cells or tissues and that they can move beyond the site of original deposition. To test this hypothesis, we use acellular assays (e.g. reactive oxygen species; dissolution; agglomeration analyses) to both identify potential benchmark nanomaterials and to predict responses in cells or tissues. Using in vitro (lung epithelial, endothelial cells) and in vivo assay systems, we have characterized responses, including cellular uptake and tissue distribution, of nanomaterials as a function of shape (using Pt), surface coating (using semiconductor quantum dots), size, and chemical composition. From these studies, it is clear that a dose metric other than mass is required to accurately predict response in acellular, in vitro, or in vivo systems and that surface area is a better predictor, at least within a given particle type. Other factors contribute to reactivity, though, including crystal phase, chemical composition, mode of synthesis, surface coating, and agglomeration state.