OVERALL: SUMMARY The UC Berkeley Superfund Research Center, in consultation with the Center’s key stakeholders and advisory boards, has identified six complex and intractable problems associated with hazardous waste sites, namely how to: 1) better assess risks to pregnant women, the fetus and young children; 2) protect disadvantaged communities; 3) understand the totality of chemicals communities are exposed to; 4) account for interactions between mixtures of chemicals; 5) perform on site in situ remediation without depleting valuable resources or transporting contaminated soil to other locations; and, 6) destroy persistent chemicals that are resistant to remediation. Four interactive projects (2 biomedical and 2 engineering) and 4 required cores are proposed to address these six problems though original research. Our proposed research and community engagement efforts aim to provide information and tools that will help solve these complex problems associated with Superfund contaminants and address the four mandates of the Superfund Research Program (SRP). The proposed interdisciplinary projects and cores of the UC Berkeley Center are all designed to address one or more of the four mandates as applied to chemicals high on ATSDR’s Superfund priority list, of importance to the US EPA’s Programs, and of concern to other stakeholders, including arsenic, chromium and other metals, PFAS and other halogenated contaminants. Our overall goal is to improve the remediation and understanding of the health effects of mixtures of Superfund contaminants. To achieve this, we propose to take a systems approach, a problem-solving paradigm grounded in public health concepts. Together with our Stakeholders, we will collectively form an understanding of some of the issues they face and create a bidirectional dialogue between us. We will attempt to perform basic research that informs action, learning and refining as we go. This ‘systems’ approach is central to improving public health. It is an approach that has been widely used in many public health settings and will be used as the central paradigm within our Center. Biomedical Projects 1 and 2 with the DMAC will study the effects of mixtures of contaminants on perinatal outcomes and the developing immune system. Engineering Projects 3 and 4 will develop a complementary treatment approach consisting of in situ chemical treatment in combination with biological radical systems to remediate a broad range of PFAS and other highly persistent halogenated pollutants. With Core A they will also assess the fate of the transformation products generated by the treatment process and their potential for toxicity. Core B in collaboration with Projects 1, 4 and the DMAC will address drinking water quality problems in California that exist despite sophisticated statewide water infrastructure and federal water quality laws. Core C (DMAC) will manage, store and share data from all projects and cores using FAIR guidelines and assist in...