**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS PROJECT ADDRESSES AN IMPORTANT CHALLENGE AREA OF NANOTOXICOLOGY- A DETAILED UNDERSTANDING OF THE MODE OF ACTIONS BY WHICH ENGINEERED NANOPARTICLES (NPS) INDUCE HEALTH RISKS. A LARGE NUMBER OF FOOD PRODUCTS CONTAIN ENGINEERED INORGANIC NPS, SUCH AS SILICON DIOXIDE NPS, DUE TO BOTH UNINTENTIONAL AND INTENTIONAL ADDITION. HOWEVER, A DETAILED UNDERSTANDING OF THE POTENTIAL ADVERSE EFFECTS OF FOODBORNE SILICON DIOXIDE NPS AND THE MOLECULAR MECHANISM INVOLVED IS NOT CURRENTLY AVAILABLE. OUR PRELIMINARY STUDIES DEMONSTRATED THAT ORAL INTAKE OF SILICON DIOXIDE NPS IN MICE RESULTED IN ACCUMULATION OF THE NPS IN THE LIVER AND KIDNEY, ADVERSE EFFECTS ON LIVER AND KIDNEY, TOXICITY IN REPRODUCTIVE SYSTEMS, AND DISRUPTION OF GUT MICROBIOTA. THESE ADVERSE EFFECTS OF SILICON DIOXIDE NPS TENDED TO BE STRONGER IN THE OBESE MICE THAN NON-OBESE MICE. THESE FINDINGS ARE CRITICALLY IMPORTANT BECAUSE THEY SUGGESTED A MODE OF ACTION BY WHICH FOODBORNE SILICON DIOXIDE NPS INDUCED ADVERSE HEALTH EFFECTS, AND IT ALSO DEMONSTRATED THAT CERTAIN POPULATIONS (SUCH AS THOSE WHO WERE OBESE) WERE MORE SUSCEPTIBLE TO THE SILICON DIOXIDE NPS-INDUCED ADVERSE EFFECTS. TO ADDRESS THE LACK OF KNOWLEDGE ON THE HEALTH RISKS OF FOODBORNE SILICON DIOXIDE NPS, BASED ON OUR PRELIMINARY DATA, THE OVERALL OBJECTIVE OF THIS PROJECT IS TO SYSTEMATICALLY DETERMINE THE ADVERSE EFFECTS OF FOODBORNE SILICON DIOXIDE NPS AND ELUCIDATE THE MOLECULAR MECHANISMS INVOLVED IN DIFFERENT POPULATIONS INCLUDING THOSE POTENTIALLY MORE SUSCEPTIBLE TO THE ADVERSE EFFECTS OF SILICON DIOXIDE NPS, SUCH AS CHILDREN AND OBESE INDIVIDUALS. THE KNOWLEDGE GAINED FROM THIS PROJECT IS CRITICALLY IMPORTANT FOR ENSURING THE SAFETY OF A WIDE RANGE OF FOOD PRODUCTS THAT MAY CONTAIN SILICON DIOXIDE NPS.