Metal Mixtures & Children's Health

Harvard School of Public Health  

Metal Mixtures And Children's Health
Joe Brain, Sc.D.
brain@hsph.harvard.edu
http://www.hsph.harvard.edu/niehs/children/index.html

Project Description

The Center for Children's Environmental Health and Disease Prevention Research addresses the concerns of a community living in the Tar Creek Superfund site of Oklahoma - an area highly contaminated by metals (lead, cadmium, iron, manganese, and others) in mining waste and populated by many residents of Native American descent. The overall goal of the Center is to take a highly innovative and integrated approach to addressing a "real world" problem, i.e., the potential of the mixtures of metals that are present in "chat" (mining waste) to interact with each other in terms of exposure, absorption, dose, and adverse effects on the development of children. The Center pursues four Research Projects with the support of four Cores. Project 1 is a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions. Project 2 assesses the utility of size fractionation and sequential extraction studies for characterizing chat, conduct a nested case-control study of the determinants of high versus low burdens of metals amongst children participating in Project 1, and produces standardized "homogenized chat" for Projects 3 and 4. Project 3 investigates the expression of binding and transporter molecules for metal transport and the corresponding pharmacokinetics of metals from the lung and gut to the blood, CNS and other organs as they relate to pregnant rats and their weanlings. Project 4 examines the effect of pre- and neo-natal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats. The effect of simple mixtures of metals is being compared with the effect of "homogenized chat" in both Projects 3 and 4. The potential effect of stress from living near toxic waste is being explored in Project 1 and the potential modifying effect of stress on metals neurotoxicity is also being explored in Project 4. The Administrative, Analytical Chemistry, and Biostatistics Cores enables Center investigators to integrate and support fully research. The Community Outreach and Translation Core utilizes an innovative portfolio of outreach activities developed in conjunction with a broadly-based Community Advisory Board to develop awareness and influence behaviors and health practices in order to prevent adverse health effects in children from exposure to metals in mining waste.

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Project Highlights

In the Center’s initial experimental studies in which investigators administered ⁵⁴MnCl² and ⁵⁹FeCl³ to rats, investigators found that the absorbed dose of metals depends on route of entry and duration with results indicating that the importance of uptake from the nose and lungs may be under-appreciated.  These data will be useful in assessing the relative risks for metal toxicity of various exposures to metals.  Center investigators have also provided the first detailed analysis of the expression pattern and regulation of proteins involved in iron transport in the lungs.

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