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Metal Mixtures and Children’s Health
EPA Grant Number: R831725Center: Harvard Center for Children’s Environmental Health and Disease Prevention Research
Center Director: Hu, Howard
Title: Metal Mixtures and Children’s Health
Investigators: Hu, Howard
Current Investigators: Hu, Howard , Backus, Ann , Brain, Joseph D. , Hatley, Earl , Jim, Rebecca , Schwartz, Joel , Shine, James P. , Spengler, John D.
Institution: Harvard School of Public Health
EPA Project Officer: Fields, Nigel
Project Period: April 1, 2004 through March 31, 2009
Project Amount: $7,894,185
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:We have proposed to establish a Center for Children’s Environmental Health and Disease Prevention Research that 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.
Approach:Our overall goal 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. Our Center will pursue four Research Projects with the support of four Cores. Project 1 will be 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 will assess 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 produce standardized “homogenized chat” for Projects 3 and 4. Project 3 will investigate 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 will examine 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 will be compared with the effect of “homogenized chat” in both Projects 3 and 4. The potential effect of stress from living near toxic waste will be explored in Project 1 and the potential modifying effect of stress on metals neurotoxicity will also be explored in Project 4. Our Administrative, Analytical Chemistry, and Biostatistics Cores will enable us to fully integrate and support our research, and our Community Outreach and Translation Core will utilize 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.
Expected Results:We expect to better understand (1) the interaction between toxic metals in terms of migration from sources; absorption from the respiratory and gastrointestinal tracts; and neurotoxicity in both experimental animals and children participating in our community-based epidemiologic study; (2) the potential modifying effect of stress on the toxicity of metals; (3) the major environmental and lifestyle determinants of high metal burdens amongst community residents; and (4) periods of vulnerability to metals toxicity during pregnancy. We will also expect that (5) the nutritional and lifestyle intervention we develop and test in a quasi-experimental design in Project 1 will result in significant lowering of toxic metals exposure. Finally, we expect that (6) the activities of our Community Outreach and Translation Core will result in a public that is better-informed and prepared to mitigate the toxic effects of metals.
Journal Articles: 16 Displayed | Download in RIS Format
| Other center views: | All 22 publications | 16 publications in selected types | All 16 journal articles |
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Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 2006;34(3):330-337. |
R831725 (2005) R831725C003 (2005) |
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Heilig EA, Thompson KJ, Molina RM, Ivanov AR, Brain JD, Wessling-Resnick M. Manganese and iron transport across pulmonary epithelium. American Journal of Physiology–Lung Cellular and Molecular Physiology 2006;290(6):L1247-L1259. |
R831725 (2005) R831725C003 (2005) |
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Heilig E, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats. American Journal of Physiology–Lung Cellular and Molecular Physiology 2005;288(5):L887-L893. |
R831725C003 (2005) |
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Heilig E, Molina R, Ivanov A, Brain JD, Wessling-Resnick M. Manganese transport across pulmonary epithelium. American Journal of Physiology Lung Cellular and Molecular Physiology 2006;290:1247-1259. |
R831725 (2005) |
not available |
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Hu H, Tellez-Rojo MM, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, Schwartz J, Schnaas L, Mercado-Garca A, Hernandez-Avila M. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environmental Health Perspectives 2006;114:1730-1735. |
R831725 (2005) |
not available |
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Hu H, Shine J, Wright RO. The challenge posed to children’s health by mixtures of toxic waste: the Tar Creek Superfund Site as a case-study. Pediatric Clinics of North America 2007;54(1):155-75. |
R831725 (2005) |
not available |
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Lanphear BP, Wright RO, Dietrich KN. Environmental neurotoxins. Pediatrics in Review 2005;26(6):191-198. |
R831725C001 (2005) R829389 (2003) R829389 (2004) R829389 (2005) |
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Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu H, Rich-Edwards JW, Gillman MW. Maternal fish consumption, hair mercury, and infant cognition in a U.S. cohort. Environmental Health Perspectives 2005;113(10):1376-1380. |
R831725C001 (2005) |
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Schaider LA, Senn DB, Brabander DJ, McCarthy KD and JP Shine. Characterization of zinc, lead and cadmium in mine waste: Implications for transport, exposure, and bioavailability. Environmental Science & Technology 2007;41(11):4164-4171. |
R831725 (2005) |
not available |
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Tellez-Rojo MM, Bellinger DC, Lamadrid-Figueroa H, Schaas-Arrieta,L, Arroyo-Quiroz C, Mercado-Garcia A, Wright RO, Hernandez-Avila M, Hu H. Longitudinal associations between blood lead concentration <10 μg/dL and neurobehavioral development in environmentally-exposed children in Mexico City. Pediatrics 2006;118(2):e323-30. |
R831725 (2005) |
not available |
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Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. Journal of Nutrition 2006;136(12):3010-3014. |
R831725 (2005) |
not available |
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Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicology and Applied Pharmacology 2006;210(1-2):17-23. |
R831725 (2005) R831725C003 (2005) |
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Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. American Journal of Physiological Gastrointestinal and Liver Physiology 2007;293:G640-644. |
R831725 (2005) |
not available |
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Thompson K, Molina R, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. Federation of American Societies for Experimental Biology Journal 2007;21(1):223-30. |
R831725 (2005) |
not available |
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Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. Neurotoxicology 2006;27(2):210-216. |
R831725 (2005) R831725C001 (2005) |
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Wright RO, Baccarelli A. Metals and neurotoxicology. Journal of Nutrition 2007; 137(12):2809-13. |
R831725 (2005) |
not available |
children, Native American, tribal, mixtures, lead, PBPK, community, Superfund, intervention,
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ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, Arsenic, Risk Assessment, Health Risk Assessment, Epidemiology, Immunology, Children's Health, Biochemistry, Environmental Chemistry, neurodevelopmental toxicity, developmental toxicity, children's environmental health, mining waste, community-based intervention, biological markers, metals
Progress and Final Reports:
2004 Progress Report
2005 Progress Report
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831725C001 Metals, Nutrition, and Stress in Child Development
R831725C002 Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport, and Exposure Patterns
R831725C003 Manganese, Iron, Cadmium, and Lead Transport from the Environment to Critical Organs During Gestation and Early Development in a Rat Model
R831725C004 Metals Neurotoxicity Research Project