Project Summary In the last decade, the use of engineered nanomaterials (NMs) (man-made materials with at least one dimension < 100 nm) has exponentially increased with their incorporation into new or developing technologies. More industries are using these NMs as components of sunscreens and cosmetics, drug delivery systems, structural materials, semiconductors, and sensors, as a result of their enhanced properties (strength, stiffness, electrical characteristics, and chemical and biological reactivity). However, these beneficial characteristics may also confer other detrimental properties once in contact with biological systems. Even though the number of NMs entering the market is increasing every year, there is a lack of information regarding the degree and conditions in which workers and consumers are exposed to these nanomaterials. Needed is a means to rapidly and reliably assess the toxicological properties of the increasing number of NMs, and to do so in a manner that can provide physiologically relevant toxicological information. Our project addresses this need with a novel approach for the direct exposure of air-liquid interface (ALI) cell cultures, both as monolayer and more complex cultures, to airborne NMs. Our approach is shown to be efficient and reproducible, providing results in minimal exposure times, even under environmentally realistic conditions. This project will carry this approach forward to provide a robust, versatile and compact device for exposing ALI cell cultures to aerosolized NMs. Together with rapid development of new methods and assays to cheaply and rapidly asses the biological effects of toxicants, our device will provide a new tool to study the mechanisms by which exposure to airborne NMs may lead to injury and/or disease, and improve our ability to examine and predict possible mechanisms of action of NMs.