Superfund Metal Mixtures, Biomarkers and Neurodevelopment

Metal mixtures, such as lead, arsenic and manganese, are common in Superfund sites. The health effects secondary to joint exposure to combinations of metals is a critical public health issue, as this exposure scenario is more reflective of the real-world situation. Children are particularly vulnerable to environmental contamination because of physical, behavioral, and biological factors. These factors both increase exposure levels and increase the toxic effects of chemicals after exposure. Genetic susceptibility to metals may be more pronounced in children due to changes in gene expression that correspond to developmental stages. Furthermore, metals are a special case of environmental contaminant as they do not degrade, but are sensitive to changing redox conditions, which alter their bioavailability. This makes modeling exposure difficult, particularly when time and human activity alter redox conditions in the environment. In this program, 6 research projects will conduct integrated research on environmental metals in water and soil, as well as biological research on metals and their mixtures in children. The effects of arsenic and manganese on neurodevelopment remain poorly understood, and critical questions also remain regarding individual differences in susceptibility to metals (even lead) and whether combinations of metals are synergistically toxic. Overall, our program consists of nonbiomedical studies on site characterization, soil metals and water metals, biomedical studies of toxicogenomics in cell cultures, and biomedical research in human populations on the joint effects of metals on neurodevelopment. We will also measure genetic susceptibility to metals in a state-of-the-art genome wide study integrated among 3 cohorts with similar design, pooling unique resources to overcome previous barriers to studying genetic susceptibility and mixed metal exposure.