The U.S. Food and Drug Administration (FDA) heavily relies on animal models to predict the toxicity and efficacy of new drugs and other substances. Latest technological advances in synthetic biology, organ-on-a-chip, systems biology and bioinformatics have created new opportunities to improve FDA’s predictive ability, while reducing and/or refining animal testing. In this seminar, I will introduce a new alternative method, developed in our laboratory, for predicting the acute inhalation toxicity of nanoparticles and nano-enabled consumer products, including e-cigarette aerosols. This new animal-free and cell-free method is based on high-fidelity biophysical simulations of the pulmonary surfactant film at the air-water surface of the lung using a smart droplet technique. It will be shown that this droplet method is capable of mimicking the highly dynamic interfacial mechanics of the alveolar surface, and quantitatively predicting the toxicity of inhaled particles and aerosols. This method holds great promise to be developed into a new alternative method for studying nano-bio interactions in the lung.