** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MANY NANOPARTICLES (NPS) ARE DEVELOPED TO MEET THE EMERGING APPLICATIONS IN FOOD ADDITIVES, FOOD PACKAGING, AND NUTRIENT ENCAPSULATION. CURRENT TOXICITY STUDIES ARE MAINLY AVAILABLE FOR INORGANIC NPS SUCH AS THOSE OF TITANIUM DIOXIDE AND ZINC OXIDE. THE SAFETY OF MANY NEWLY DEVELOPED NPS IS THUS LIMITED, WHICH INCLUDE THE NPS DEVELOPED FROM ORGANIC ORIGINS, SUCH AS NPS OF CURCUMIN AND RESVERATROL. WE WILL FABRICATE NPS OF CURCUMIN AND RESVERATROL AS MODEL ENGINEERED FOOD NPS AND SYSTEMATICALLY EVALUATE THEIR HEALTH IMPACTS. WE WILL USE TECHNIQUES TO CHARACTERIZE AND EVALUATE THE NPS FOR THE EFFECTS OF PARTICLE SIZE, SURFACE CHARGE/CHEMISTRY, MORPHOLOGY, COLLOIDAL STABILITY, AND DISSOLUTION KINETICS ON THE TOXICITY OF THOSE NPS IN DIFFERENT FOOD SYSTEMS AND DIGESTIVE FLUIDS. METHODOLOGIES WILL BE ESTABLISHED TO UNDERSTAND THE BEHAVIOR OF VARIOUS NPS AND THEIR INTERACTION WITH FOOD COMPONENTS AND GASTROINTESTINAL FLUIDS AT DIFFERENT DISSOLUTION CONDITIONS (I.E. PH, IONIC STRENGTH, AND ENZYME). TO ENSURE RESPONSIBLE DEVELOPMENT AND DEPLOYMENT OF THE NPS, WE WILL EVALUATE THE FACTORS AND IDENTIFY MECHANISMS CONTRIBUTING TO THE NANOTOXICITIES OF THE NPS USING IN VITRO AND IN VIVO MULTI-ASSAY-BASED EVALUATION. RESULTS OF THIS PROJECT WILL ADVANCE THE IDENTIFICATION OF MULTIPLE FACTORS AND EXPOSURE LEVELS CONTRIBUTING TO TOXICITIES OF NPS TO ENSURE HUMAN, ANIMAL, AND ENVIRONMENTAL HEALTH, AND LAY DOWN THE FOUNDATION FOR SAFE DEVELOPMENT OF NANOTECHNOLOGY WITH SIGNIFICANT SOCIETAL, ENVIRONMENTAL, AND ECONOMIC IMPACTS.