Abstract Perinatal exposure to lead remains a highly relevant pediatric environmental health problem, despite tremendous awareness and remediation efforts. Even at low levels, exposure to lead adversely impacts neurodevelopment; however, children are not exposed to lead in isolation. Most children are chronically exposed to hundreds of chemicals. Recent studies have found that pregnant women and children living in some areas of Durham, NC have elevated exposures to both lead and cadmium. Our preliminary data demonstrate that lead and cadmium are also elevated in surface soils in some areas of Durham, as are the levels of polycyclic aromatic hydrocarbons (PAHs). Metals and PAHs also commonly co-occur in contaminated sites (e.g., Superfund Sites and Brownfields). Therefore, people living near these sites are exposed to mixtures of metals and PAHs simultaneously. While lead is a well-studied neurotoxicant, little research has been conducted to understand co- exposure to these compounds and their potential developmental impacts. The Duke University Superfund Research Center (DUSRC) seeks to better address this data gap and contribute new information and resources to better address potential health risks. Here we propose a biomedical project (Project 1) within the DUSRC to address prenatal exposure to mixtures of PAHs and metals in a community with known co-exposure. We hypothesize that prenatal exposure to metals and PAHs is associated with neurodevelopmental changes that are greater than the impacts of lead alone. We will first characterize exposures in a cohort of 400 pregnant women, leveraging resources available from an ongoing longitudinal study. Metals will be measured in maternal blood samples collected during prenatal care visits, while PAHs (and other organic contaminants) will be measured in silicone wristbands worn for a week in each trimester of pregnancy. Cognitive and behavioral assessments will be carried out with children during the first three years of life using a novel personal monitor and standard clinical assessments. Furthermore, we will use a novel geochemical isotopic tracing approach to identify the primary sources of lead in a subgroup of the cohort that has the highest levels of exposures. This project directly addresses Superfund Mandates 1, 2 and 3. It will use advanced techniques to investigate the effects of hazardous substances on human health, while also developing new methods to evaluate lead exposure risks and identifying the primary exposure pathway to support targeted exposure mitigation strategies.