Project Summary Phthalates are a type of plasticizer that are used to make rigid polyvinyl chloride (PVC) plastic flexible. In medical devices, phthalate levels have been reported to be between 20-80% of a product’s weight depending on the type of device; however, questions have arisen over their safety. The most common phthalate plasticizer used in PVC medical devices is di(2-ethylhexyl) phthalate (DEHP). Patients undergoing cardiac surgery involving the use of a cardiopulmonary bypass (CPB) circuit are exposed to significant levels of DEHP from blood products, circuitry tubing, bypass cannulas, and endotracheal tubes. Despite the immeasurable benefits of plastics – there is increasing concern over the potential health risks of phthalate chemical exposures. Accordingly, there is an urgent need to develop and adopt safer alternatives to be used in pediatric CPB. The proposed research project will address this need by evaluating the cardiotoxic effects of DEHP on the pediatric heart and investigating potential mitigation strategies to reduce exposure to toxic phthalate chemicals. Aim 1 will assess the direct effects of phthalate plasticizers on human pediatric cardiac electrophysiology and contractility. Aim 2 will determine the efficacy of potential mitigation strategies to reduce phthalate exposure and improve cardiac outcomes. The latter will include investigating the cardiac safety profile of commercially available DEHP- free alternatives and the utility of using cell washing to remove phthalate plasticizers from cardiopulmonary bypass fluids. The results of this proposal will largely be applicable to the fields of cardiology, with the potential to inform regulatory decision making over the use of phthalate plasticizers in medical device manufacturing. This is particularly important for medical devices that are used to treat vulnerable neonates and infants undergoing cardiopulmonary bypass. This application contains a three-year training plan that will further my scientific development, by building upon the expertise of my Sponsor (Dr. Posnack with expertise in cardiac electrophysiology and cardiotoxicity) and co-Sponsor (Dr. Ishibashi with experience in preclinical models and pediatric cardiac surgery). I will also benefit from a broader group of collaborators, who will provide insight into clinical relevance and experimental techniques. This training proposal will expand my scientific understanding of pediatric cardiovascular physiology, plasticizer toxicity, and clinically relevant models while supporting my future goal to lead a translational research laboratory at a top children’s hospital.