Harvard School of Public Health
Superfund Research Program
Superfund Metal Mixtures, Biomarkers and Neurodevelopment
Center Director: David C. Bellinger
Grant Number: P42ES016454
Funding Period: 2010-2014
Metal mixtures, such as lead, arsenic and manganese, are common in Superfund sites and 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. 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 which 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, six research projects are conducting 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, the 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. Researchers are also measuring genetic susceptibility to metals in a state-of-the-art genome-wide study integrated among three cohorts with similar design, pooling unique resources to overcome previous barriers to studying genetic susceptibility and mixed metal exposure.