Ultrafine Particle Generator and Scanning Mobility Particle Sizer Integrated System - ABSTRACT The University of Rochester has a long, internationally recognized history of research about the effects of airborne substances in the lungs and other organ systems. Indeed, Rochester is the birthplace of inhalation toxicology, as technology was developed here during the Manhattan Project to conduct studies on the effects of radionuclides. The infrastructure has grown over the decades into a dedicated Inhalation Exposure Facility (IEF) that supports basic and translational research about how airborne substances, by themselves or in combination with other stressors, contribute to cumulative health risk across the lifespan. Ambient air pollution is a mixture of particles, gases, and semi-volatile constituents that exhibits temporal and spatial variability in composition and concentration. It continues to be a significant threat to human health. Ambient pollutant fine and ultrafine (UFP, <100 nm in airborne diameter) particles are largely combustion- derived, e.g., from industrial and traffic sources, and have carbonaceous, inorganic salt, and metal/metal oxides compositional signatures. UFPs are of particular interest as drivers of adverse health effects due to their high number concentrations in air, large surface area-to-mass ratios, ability to deposit efficiently throughout the respiratory tract, and potential for transport to extrapulmonary tissues upon inhalation exposure. The study of UFP exposure-related health effects is an area of strength for the Rochester IEF. Its infrastructure has supported ground-breaking discoveries about the effects of UFP in the lung and extrapulmonary organ systems (cardiovascular, central nervous); transport of inhaled UFP to the brain via the olfactory system; perturbations in learning, memory, and impulsivity behaviors; and the mechanisms that lead to these adverse effects. The IEF tools for generating and characterizing UFP exposures are heavily utilized by multiple investigators who are funded by NIH and other agencies. To support these funded projects and to ensure that the research is conducted in a rigorous manner, replacement of and upgrades to the equipment that is used to generate, monitor, and characterize UFP-rich aerosols for inhalation exposures are urgently needed. Thus, this application seeks support to purchase a new integrated UFP aerosol generation and characterization system with modernized safety and monitoring features. This integrated system allows direct translation between species: knowledge about human exposures to UFP can be leveraged to conduct evidence-generating mechanistic studies in animal models or cell culture systems and, vice versa, health outcome data from basic science models can be translated to human-relevant exposures. Without this system that represents the state-of-the-art, the translatability of findings from UFP inhalation exposures is significantly weakened and, by extension, the impact of findings on evidence-based decision making.