2004 Progress Report: Metal Mixtures and Children’s Health

EPA Grant Number: R831725
Center: 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 , Backus, Ann , Brain, Joseph D. , Hatley, Earl , Jim, Rebecca , Schwartz, Joel , Shine, James P. , Spengler, John D.
Current Investigators: Hu, Howard , Brain, Joseph D.
Institution: Harvard T.H. Chan School of Public Health
EPA Project Officer: Callan, Richard
Project Period: June 1, 2004 through May 31, 2009 (Extended to May 31, 2011)
Project Period Covered by this Report: June 1, 2004 through May 31, 2005
Project Amount: $7,894,185
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health

Objective:

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 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, central nervous system, and other organs as they relate to pregnant rats and their weanlings.  Project 4 will examine the effect of pre- and neonatal 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 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 also will 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 (CAB) to develop awareness and influence behaviors and health practices to prevent adverse health effects in children from exposure to metals in mining waste.

Progress Summary:

Initiating the Center’s work and making progress was slow for some aspects of the Center’s portfolio of activities and rapid for others.  In general, several components of the field studies that comprise Projects 1 and 2 were delayed by the need to lay further groundwork in cultivating support of the community, establish communications with other government and community stakeholders, finalize our sampling protocols, and process financial subcontracts with our community-based partners.  Processing financial subcontracts and accommodating the split nature of the Center’s award (from the National Institute of Environmental Health Sciences [NIEHS] and the U.S. Environmental Protection Agency [EPA]) also delayed the ability to make progress in purchasing equipment and renting space, issues that particularly affected Project 4 and the Community Outreach and Translation Core (COTC).  We made substantial progress, however, with respect to the birth cohort epidemiologic study component of Project 1 and the animal research in Project 3.  We also made progress in methods development related to our Chemistry Core and Biostatistics Core; developed outreach tools for the COTC; and quickly identified two outstanding individuals to be the Center scientists—both already are hard at work with support from the Administrative Core.

Overall, although a modest reduction in the extent of our data collection and outreach likely will be necessary because of cuts sustained in the size of our awards from NIEHS and EPA in relation to what we had originally proposed, our plans with respect to our specific aims remain unchanged.

The Center also was pleased to participate in the panel presentation and discussion section involving all of the Children’s Centers at the August 2004 International Society for Environmental Epidemiology Annual Conference in New York (Hu and Brain, 2004; see Core A:  Administration below) and a meeting of all of the Children’s Centers that occurred at NIEHS in December 2004.

Core A:  Administration

The Administrative Core has concentrated on securing and operationalizing the budgets and subcontracts for each of the projects and cores; expanding and recruiting more members for the External Advisory Committee (in response to the terms and conditions of the EPA component of the Center grant); working with members of the community to update and operationalize the CAB; working with members of the community to establish a Native American Subcommittee to the CAB; and introducing the work of the Center and communicating with other stakeholders in the Tar Creek Superfund Site, including senior members of EPA (the Superfund Program, the Children’s Centers Program, Region 6), the State of Oklahoma, the University of Oklahoma, and others.  Our first External Advisory Committee meeting is scheduled for March 28, 2005, and the Administrative Core will be busy ensuring that the meeting optimally utilizes the skills and advice of the Committee’s experts.

To facilitate overall outreach and communications, the Administrative Core has established a Web site that provides key information on each of the projects and cores and that we will use for updates on events, publications, and other information.

The Administrative Core also is pleased to have recruited two outstanding scientists as the first two official Center scientists, Drs. Adrienne Ettinger and David Senn.  Dr. Ettinger has a Sc.D. in environmental epidemiology and years of experience at the Centers for Disease Control and Prevention and has conducted groundbreaking research on metals in human breast milk.  Dr. Senn has a Ph.D. in civil and environmental engineering and years of experience in research on heavy metals mobility, speciation, and bioavailability.  Their combination of skills and work will contribute heavily toward the successful integration and conduct of our field research.  Both already have visited the Tar Creek Site several times, giving presentations and overseeing the collection of data.

Update on Projects.  Projects 1 and 2 are field research projects that require some piloting or scoping work to be conducted prior to finalizing the planning for these projects.  This scoping work currently is underway.  Projects 3 and 4 primarily are laboratory research projects using previously tested experimental methods.  The project plans for these projects already are in place.

Update on Project 1.  Project 1 is an expansion of an ongoing observational birth cohort study.  This new project will comprise both observational aims on exposures to metal mixtures, as well as nutritional and community-level interventions.  Researchers currently are collecting and analyzing pilot data from the first phase of the research.  The information gained from this pilot work will be used to lay the groundwork for the second phase of subject recruitment and to improve on existing methods for data management, standard operating procedures (SOPs), analysis, and reporting.  Our goal was to have the Quality Assurance Project Plan (QAPP) for Project 1 ready by April 2005.

Update on Project 2.  Project 2 is a multimedia exposure study.  Researchers have prepared a project plan to describe the sampling program for a scoping or pilot study scheduled in late January.  Based on what is learned from the pilot study, the QAPP for Project 2 will be developed.  Our goal for Project 2 was to have the QAPP finalized by May 2005.

Update on Project 3.  Project 3 involves the development of a rat model of manganese, iron, cadmium, and lead transport from the environment to critical organs during gestation.  A QAPP for the project was prepared by Ramon Molina, the Project Co-Director, and reviewed by the Project Director and Co-Director and the Quality Assurance (QA) Officer on December 16, 2004.  The objective of the QAPP is to outline the planning process for the project and to document that all SOPs and protocols required to complete the work have been prepared.

Update on Project 4.  Project 4 is a metal neurotoxicity research project.  The QAPP for this project was prepared by Tim Maher and Marc Weisskopf, the project’s principal investigator (PI) and co-PI, respectively, and reviewed by the QA Officer on December 16, 2004.

Core B:  Analytical Chemistry

The Analytical Chemistry Core has two components:  the trace metal facilities and development of sampling equipment.  The trace metal facilities are maintained to serve the analysis needs of the various projects.  Trace metal analyses of blood and hair samples collected at Tar Creek, Oklahoma, continue.  Table 1 summarizes all of the metal analyses performed to date on the Tar Creek cohort of mothers and children as part of our Superfund-supported Community-Based Participation and Intervention Research Project.  With support from Project 1 of the Children’s Center, we are adding measurements of arsenic (As) in hair and cadmium (Cd) in urine.  Note that children and mothers are now being resampled as the children turn 1 year old.  There are no outstanding issues of concern.

Table 1.  Summary Statistics of Maternal and Neonatal Blood Metal Levels


Parameter

Units

n

Arithmetic  Mean (SD)

Geometric Mean (SD)

min

max

Manganese Levels

Maternal blood

µg/dL

286

2.3 (0.8)

2.2

0.9

7.7

Umbilical Cord blood

µg/dL

285

3.9 (1.5)

3.6

0.5

10.5

Infant Blood at 1 year

µg/dL

63

2.3 (1.1)

2.1

0.9

6.7

Lead  Levels

Maternal blood

µg/dL

286

0.8 (0.5)

0.7

0.1

3.1

Umbilical Cord blood

µg/dL

285

0.6 (0.4)

0.5

<LOD+

3.1

Infant Blood at 1 year

µg/dL

63

2.1 (1.4)

1.7

0.4

6.0

 Arsenic Levels

Maternal Hair

ppb

58

26.0 (45.0)

12.9

1.1

225.2

Infant Hair at 1 year

ppb

37

102.1 (93.9)

66.7

5.7

384.8

+Limit of Detection for Blood Lead = 0.012 µg/dL

Two efforts are underway for developing sampling equipment.  For one effort related to the exposure assessment activities, low-flow size-selective (PM2.5) particle samplers are being designed.  These samplers will plug into an electrical wall outlet for unattended operation for 1 to 3 months.  Prototype devices will be available for testing soon.

For the second effort, the Analytical Chemistry Core has assembled an aerosol suspension apparatus.  The experimental setup is shown in Figure 1.  Test dust from Tar Creek chat (mining waste) is dried over 24 hours prior to its use in a temperature of 50°C and aerosolized using a Fluidized Bed Aerosol Generator (TSI Model 3400A).  Aerosolized dust then passes through the Kr-85 Neutralizer to reduce the particle charge to close to the Boltzmann equilibrium distribution.  The aerosol then is introduced into a circular tube.  Isokinetic probes are placed at a distance of more than 10 times the tube diameter.  Laboratory experiments are conducted by both the Compact Cascade Impactor (CCI) and real-time instrument measurements (Scanning Mobility Particle Sizer [SMPS], Aerodynamic Particle Sizer [APS]) to classify the particles by their size and further analysis.  An assembled CCI consists of four impactor stages (PM10, PM2.5, PM1.0, and PM0.16) and an after filter.  Each stage consists of a slit-shaped acceleration nozzle and a rectangular polyurethane foam (PUF) impaction substrate (density = 0.03g/cc, Merryweather Foam, OH).  The PUF substrates are inserted easily and removed from a substrate base and securely transported to a laboratory for gravimetric or chemical analysis.

Figure 1. Aerosol Suspension  and Measuring System

Figure 1.  Aerosol Suspension and Measuring System

In February 2005, the chat samples collected this past year from Tar Creek will be separated by size and tested for metal distributions.  Bulk material of the size-separated fractions will be provided to other investigators for use in their animal studies.

Core C:  Biostatistics

As the Center was funded only 8 months ago, and we still have not received permission from EPA to collect any data per their QA/QC process, there has not been any progress for the Statistical Core with respect to data analysis.  We have, however, continued our work in developing the methods that will be necessary for data analysis as well as the knowledge necessary for applying these methods to Center data.  For instance, the Harvard School of Public Health Environmental Statistics Program invited Dr. Esben Budtz-Jorgensen to teach a 3-day short course on the theory and application of Structural Equation Models to environmental health data.  Environmental Health and Biostatistics faculty, postdoctoral fellows, and graduate students in the Center attended the course.  We also have been working on diagnostic methods for assessing goodness-of-fit in mixed effects models for repeated measures.  The methods are implemented easily in common statistical packages such as SAS, S-plus, and R.

Core D:  Community Outreach and Translation

As required by the Request for Applications, the Center includes a COTC to “develop, implement, and evaluate strategies to translate and apply the scientific findings of the Center into information for the public, policymakers, and clinical professionals to use to protect the health of children.”  The backbone of the COTC consists of seven specific aims, the interim accomplishments of which are presented below.  Outreach based on early work in Projects 1 and 2 has begun.  Projects 3 and 4, only in a very early stage of data collection, do not have any significant results on which outreach can be developed.  The COTC is administered through a subcontract to the Local Environmental Action Demanded (L.E.A.D.) Agency of Miami, Oklahoma.

In addition to the outreach planned under the COTC, the Children’s Center established a CAB whose mission is based on five of the six principles of community-based participatory research endorsed by NIEHS, namely to:  (1) promote active collaboration and participation at the community level; (2) foster colearning between community and researchers; (3) ensure that Center-sponsored research continues to be community driven; (4) disseminate results in a useful language; and (5) ensure the cultural appropriateness of research and intervention strategies.

Since the start of the Center, the composition of the CAB has changed to include one nonvoting member from each of the following:  Oklahoma State Department of Environmental Quality, EPA Region 6, and another research project based in the community, as well as the following members:

Co-Chair, Kathy Ellis—Integris Hospital
Co-Chair, Anne Anthony—Willow Crest Hospital
Dr. Bill Able—Northeastern Oklahoma College
Al Gonzales—Quapaw School
Dr. Shirley Chestnut—Grand Lake Mental Health Center
Susan Waldron—Ottawa County Health Department
Debi Wesley—Northeast Tribal Health Center
Tamara Summerfield—Quapaw Tribe
Marion Sizemore—Seneca-Cayuga Tribe
Rosanna Shepherd—Ottawa Tribe
Kim Pace—Picher Elementary School
Dr. Duane Koehler—Integris Hospital

Early in the process of drawing the community together around the Children’s Center, the CAB also called for and established a Tribal Subcommittee to ensure representation of and input from the tribes affected by the Tar Creek Superfund Site and the work of the Children’s Center. Members of record are:  Chairperson, Rosanna Shephard – Ottawa Tribe; Marion Sizemore – Senecan - Cayuga Tribe; Jason While – Cherokee Nation; Tim Kent – Quapaw Tribe; Roxanne Weldon – Eastern Shawnee Tribe; Christen Creson – Wyandote Nation; Jim Dixon – Peoria Tribe; Cody White – Modoc Tribe; and Tom Ward – Miami Tribe.  The Shawnee Nation will have a representative.  It is expected that other representatives from the tribal environmental departments will attend the Tribal Subcommittee meetings.  The mission of the Tribal Subcommittee is to promote dialogue on culturally significant issues related to tribal sovereignty.  Earl Hatley serves as the liaison between the tribes and the researchers.  In June, within 2 weeks of receiving funding, Dr. Howard Hu was a guest of the Inter-Tribal Council, presented the goals of the Children’s Center, and discussed process and other concerns with elected tribal leaders.
The COTC manages the CAB meetings.  In the initial 6 months of the grant (June 1 to December 31, 2004), the CAB met three times:  June 8, August 6, and November 16.  Topics for discussion included membership, meeting schedule and times, updates on research projects, and review of recent COTC work products.  Robert Wright, M.D., PI of Project 1, presented details about the Children’s Center at the August CAB meeting; Adrienne Ettinger, a researcher on Project 1, attended the November CAB meeting as a guest.

We have accomplished the following toward the specific aims of the COTC:

Specific Aim 1:  Compile and Summarize Information From the Literature and From the Findings of the Center-Sponsored Studies; Make Documents Available in the Public Library Tar Creek Depository.  Nursing students from Oral Roberts University (ORU) were introduced to the Children’s Center projects and teamed up with six Quapaw High School art students to design and make bookmarks.  The bookmarks, bearing 15 different messages such as, “Because they are smaller, children receive higher doses of toxicants per pound of body weight,” and “Children’s activities put them at higher risk of exposure to hazardous substances that might be in water or soil,” were placed in the Miami Public Library Tar Creek Depository for the EPA Tar Creek Superfund Site Documents and in other public places.  To discourage fishermen and the public from eating whole fish caught in the Tar Creek mining area, ORU nursing students created fish rulers with the message that eating whole fish should be discouraged.  This message is based on a 2002 study by the Oklahoma Department of Environmental Quality that found that fish fillets were safe to eat, but that “40 percent of the whole, ungutted fish, and 21 percent of the whole, gutted fish” contained lead that exceeded safe consumption levels.

Copies of the L.E.A.D. Agency newsletter (discussed below) with articles about the Children’s Center are available at the Tar Creek Depository.

Specific Aim 2:  Develop and publicize simple measures for assessing and mitigating risks of exposures to pregnant women and children.  The COTC organized two community presentations by Children’s Center researchers.  In the fall, Jim Shine, PI of Project 2, made presentations to the Tribal Subcommittee and to the general public on “The Fate of Metals.”  In November, Adrienne Ettinger, Center scientist, made a presentation entitled “Why Breastfeeding Is Still Best” at the COTC office for nursing mothers and those interested in breastfeeding and at Northeastern Oklahoma (NEO), the latter of which was videotaped for future showing on NEO Channel 13.  Local newspapers covered the event.

The newsletter published by the L.E.A.D. Agency in December contained four pages of articles on the Children’s Center, COTC, the CAB, the Tribal Subcommittee, and the work with youth.  As mentioned above, copies of the newsletter are available in the Miami Public Library, Tar Creek Depository.  They also were mailed to the L.E.A.D. Agency mailing list.

Specific Aim 3:  Use the COTC Web Site To Communicate Progress in Each of the Children’s Center’s Research Projects.  As noted in the Administration Core, a Children’s Center Web Site was created at Harvard.  This site contains information about the research projects, research cores, and Center administration.  As the research progresses, publications and research results as well as outreach activities will be published on the Web site.  The L.E.A.D. Agency Web Site, http://www.leadagency.org, also will contain research results and outreach activities and will serve as the major source for the community of information about Tar Creek activities related to the field research. The two Web sites are interlinked.

Specific Aim 4:  Arrange For and Sponsor the Participation of Center Faculty in Teaching Environmental Health Concepts.  With the taping of Dr. Ettinger’s presentation by NEO, the COTC has made the first of many contributions to the video library documentation of the Children’s Center research.  Rebecca Jim and Earl Hatley have launched discussions with NEO personnel regarding how to proceed with distance-learning for the fall of 2005.  At Harvard, lectures in the course “Principles of Environmental Health,” taught by Dr. Howard Hu, Director of the Children’s Center, were videotaped during the fall term.  Ann Backus is working on taping several Grand Rounds presentations at Harvard this spring.

Specific Aim 5:  Shape and Translate Educational Materials Into Learning Modules for High School Students.  Work in this area will begin later as results from the research projects become available.

Specific Aim 6:  Sponsor a Community Scholars Program.  Earl Hatley has identified several potential community scholars and projects. After the formal structure for the program has been developed, six scholars will be chosen to comprise the first cohort of scholars.  Their assigned mentors will be Harvard faculty or other professionals, such as professional photographers, depending on the nature of their projects.

Specific Aim 7:  Sponsor the Annual Tar Creek Conference and Arrange for Focus Group Meetings Involving Health Professionals and Community Throughout the Year.  The annual Tar Creek Conference is scheduled for May 5-6, 2005, at the Miami Civic Center, Miami, Oklahoma.

Conclusion.  The accomplishments—including the formation of a CAB and the Tribal Subcommittee, the publication of a newsletter and Web sites, and the arrangement of two public presentations, as well as the securing of office space—have provided early visibility for the Children’s Center at Tar Creek and have established a tone of collaboration among tribes, the community, and the researchers for this community-based research in the field of children’s environmental health.  We are grateful for everyone’s early contributions at the inception of this EPA/NIEHS-funded project.

Future Activities:

The investigators did not report any future activities.


Journal Articles: 25 Displayed | Download in RIS Format

Other center views: All 35 publications 26 publications in selected types All 25 journal articles
Type Citation Sub Project Document Sources
Journal Article Arora M, Weuve J, Schwartz J, Wright RO. Association of environmental cadmium exposure with pediatric dental caries. Environmental Health Perspectives 2008;116(6):821-825. R831725 (2007)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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. R831725 (2007)
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  • Journal Article Hopkins MR, Ettinger AS, Hernandez-Avila M, Schwartz J, Tellez-Rojo MM, Lamadrid-Figueroa H, Bellinger D, Hu H, Wright RO. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives 2008;116(9):1261-1266. R831725 (2009)
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  • Journal Article Hu H, Tellez-Rojo MM, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, Schwartz J, Schnaas L, Mercado-Garcia A, Hernandez-Avila M. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environmental Health Perspectives 2006;114(11):1730-1735. R831725 (2007)
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  • Journal Article 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):155-175. R831725 (2007)
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  • Journal Article Lanphear BP, Wright RO, Dietrich KN. Environmental neurotoxins. Pediatrics in Review 2005;26(6):191-198. R831725 (2009)
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  • Journal Article 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. R831725 (2007)
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  • Journal Article Ortega Garcia JA, Carrizo Gallardo D, Ferris i Tortajada J, Garcia MM, Grimalt JO. Meconium and neurotoxicants: searching for a prenatal exposure timing. Archives of Disease in Childhood 2006;91(8):642-646. R831725 (2009)
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  • Journal Article Ostrea Jr EM, Morales V, Ngoumgna E, Prescilla R, Tan E, Hernandez E, Ramirez GB, Cifra HL, Manlapaz ML. Prevalence of fetal exposure to environmental toxins as determined by meconium analysis. NeuroToxicology 2002;23(3):329-339. R831725 (2009)
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  • Journal Article Schaider LA, Senn DB, Brabander DJ, McCarthy KD, Shine JP. Characterization of zinc, lead, and cadmium in mine waste: implications for transport, exposure, and bioavailability. Environmental Science and Technology 2007;41(11):4164-4171. R831725 (2007)
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  • Journal Article Surkan PJ, Schnaas L, Wright RJ, Tellez-Rojo MM, Lamadrid-Figueroa H, Hu H, Hernandez-Avila EM, Bellinger DC, Schwartz J, Perroni E, Wright RO. Maternal self-esteem, exposure to lead, and child neurodevelopment. NeuroToxicology 2008;29(2):278-285. R831725 (2007)
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  • Journal Article Tellez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcia A, Schnaas-Arrieta L, Wright RO, Hernandez-Avila M, Hu H. Longitudinal associations between blood lead concentrations lower than 10 μg/dL and neurobehavioral development in environmentally exposed children in Mexico City. Pediatrics 2006;118(2):e323-e330. R831725 (2007)
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  • Journal Article Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. Journal of Nutrition 2006;136(12):3010-3014. R831725 (2007)
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  • Journal Article 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)
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  • Journal Article Thompson K, Molina RM, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB Journal 2007;21(1):223-230. R831725 (2007)
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  • Journal Article Thompson K, Molina RM, Donaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. American Journal of Physiology-Gastrointestinal and Liver Physiology 2007;293(3):G640-G644. R831725 (2007)
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  • Journal Article Turker G, Ergen K, Karakoc Y, Arisoy AE, Barutcu UB. Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city. Biology of the Neonate 2006;89(4):244-250. R831725 (2009)
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  • Abstract: Karger-Abstract
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  • Journal Article 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)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2005)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Wright RO, Baccarelli A. Metals and neurotoxicology. The Journal of Nutrition 2007;137(12):2809-2813. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: OUP-Full Text HTML
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  • Other: OUP-Full Text PDF
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  • Journal Article Wright RO, Fields N. Therapeutics and toxicology. Current Opinion in Pediatrics 2008;20(2):171. R831725 (2009)
    R831725C001 (2008)
  • Abstract from PubMed
  • Abstract: Ovid-Excerpt
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  • Other: Current Opinion in Pediatrics-Citation
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  • Journal Article Wright RO. Neurotoxicology: what can context teach us? Journal of Pediatrics 2008;152(2):155-157. R831725 (2009)
    R831725C001 (2008)
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  • Abstract from PubMed
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  • Full-text: The Journal of Pediatrics-Full Text HTML
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  • Other: Journal of Pediatrics-Full Text PDF
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  • Journal Article Wright RO. New morbidities: new challenges. Current Opinion in Pediatrics 2009;21(2):220-221. R831725 (2009)
    R831725C001 (2008)
  • Abstract from PubMed
  • Full-text: LWW-Full Text HTML
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  • Journal Article Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO. Maternal blood manganese levels and infant birth weight. Epidemiology 2009;20(3):367-373. R831725 (2009)
    R831725C001 (2008)
  • Full-text from PubMed
  • Abstract from PubMed
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  • Abstract: Epidemiology-Abstract
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  • Supplemental Keywords:

    children, Native American tribal, mixtures, lead, PBPK, community, Superfund, intervention, environmental management,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Epidemiology, Arsenic, Biochemistry, Children's Health, Immunology, Risk Assessment, community-based intervention, developmental toxicity, Human Health Risk Assessment, neurodevelopmental toxicity, children's environmental health, biological markers, mining waste

    Relevant Websites:

    http://www.hsph.harvard.edu/niehs/children Exit

    Progress and Final Reports:

    Original Abstract
  • 2005 Progress Report
  • 2006
  • 2007 Progress Report
  • 2008
  • 2009 Progress Report
  • Final
  • 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