2005 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, 2005 through May 31, 2006
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 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 also will be explored in Project 4.  The Administrative, Analytical Chemistry, and Biostatistics Cores will enable the Center to fully integrate and support its research, and the Community Outreach and Translation Core (COTC) 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:

During Year 2, we have made substantial progress in all of the Center’s projects and cores.  Among the highlights are:  (1) Project 1’s enrollment of 425 mother-infant pairs in our birth cohort and the publication of a pilot study of sixth graders demonstrating significant inverse relationships of both hair As and Mn with IQ; (2) Project 2’s intensive collection and analysis (and, in many samples, size fractionation and speciation) of mining waste samples from six major chat piles, water and air samples from multiple locations, and household exposure media samples from 35 residences of infants participating in the Project 1 birth cohort; (3) Project 3’s multiple published or submitted studies comparing efficacy of routes of absorption and organ deposition of Fe, Mn (during differing stages of development), and multiple metals in actual chat samples and the influence of iron status on the absorption of other metals; and (4) Project 4’s initial studies demonstrating the need to adjust oral manganese dosing to accommodate collateral effects on drinking behavior in our experimental rats.  With regards to the cores, the Administrative Core completed and submitted a full Quality Management Plan and organized a first External Advisory Committee Meeting while continuing the monthly schedule of project and core meetings and Center Scientist Program.  The Chemistry Core accommodated a major increase in the number of samples for Project 2; successfully constructed, tested, and implemented a new apparatus for aerosolizing chat samples to isolate respirable particles for Project 3; and established a new collaboration (at Wellesley College).  The Biostatistics Core expanded its data management capability to accommodate the marked increase in Project 1 data, supervised ongoing data analyses, and developed methods for examining multilevel data with spatial correlation.  The COTC has continued to sponsor CAB meetings, onsite outreach by our investigators, and a visit by the Executive Director of the Harvard School of Public Health (HSPH) Human Subjects Committee; disseminate written, oral testimony, and Web-based educational materials; participate in the 2005 Annual Tar Creek Conference; and initiate a Visiting Scholars program.

The Center also participated in the Centers for Children’s Environmental Health Research Workshop, July 11-12, 2005, at the U.S. Environmental Protection Agency (EPA) facility in Research Triangle Park, North Carolina.  In addition to making presentations, several of our investigators participated in the breakout sessions.  Following the meeting, several potential collaborations between investigators in the Center and EPA scientists are in development, such as work on iron and the lung (Dr. Marianne Wessling-Resnick of Project 3 and Dr. Andrew Ghio of EPA) and work on chemical analyses of mining waste (Dr. Jim Shine of Project 2, Dr. John Spengler of the Chemistry Core, and scientists at the EPA National Exposure Research Laboratory).

Core A:  Administration

During Year 2, the Administrative Core organized and executed the first meeting of the Center’s External Advisory Committee, continued to work with members of the community to update and operationalize the CAB and the Native American Subcommittee to the CAB, continued to organize and execute the Center’s monthly meeting of all Project and Core Leaders, and worked hard at the scientific integration of our work.

The Administrative Core also continued the operations and updating of the Center Web site (http://www.hsph.harvard.edu/niehs/children) that provides key information on each of the projects and cores and that has been used for updates on events, publications, and other information.  The Administrative Core also has continued to support our two outstanding “Center Scientists,” Drs. Adrienne Ettinger and David Senn. 

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, they are adding measurements of As in hair and 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 and Hair Metal Levels


Parameter

Units

N

Arithmetic  Mean (SD)

Median

Min

Max

Manganese Levels

Maternal blood

µg/dL

366

2.3 (0.8)

2.2

0.9

7.7

Umbilical Cord blood

µg/dL

364

4.0 (1.5)

4.0

0.5

10.5

Infant Blood at 1 year

µg/dL

70

2.2 (1.1)

1.9

0.9

6.7

Lead  Levels

Maternal blood

µg/dL

366

0.8 (0.4)

0.7

0.03

3.1

Umbilical Cord blood

µg/dL

364

0.5 (0.4)

0.5

<LOD+

3.1

Infant Blood at 1 year

µg/dL

70

2.1 (1.4)

1.8

0.4

6.0

 Arsenic Levels

Maternal Hair

ppb

75

25.8 (40.3)

12.6

1.1

225.2

Infant Hair at 1 year

ppb

42

96.8 (89.5)

61.1

5.7

384.8

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

Additionally, the trace metals facility has been participating in acid digestions and subsequent inductively coupled plasma mass spectroscopy analysis of tap water samples collected from homes in Tar Creek, Oklahoma as part of the Project 2 exposure assessment study.  Table 2 summarizes the drinking water samples analyzed to date.

Table 2.  Metal Concentrations in Tap Water from Homes in Tar Creek, Oklahoma

 

Lead
(ppb)

Manganese
(ppb)

Cadmium
(ppb)

Zinc
(ppb)

Copper
(ppb)

Arsenic
(ppb)

 Sample Size

38

38

38

38

38

38

% Below LOD

26%

N/A

11%

N/A

N/A

3%

Minimum

LOD

0.04

LOD

4.00

0.27

LOD

Mean

0.41

2.16

0.05

52.38

11.29

0.27

Maximum

3.21

12.34

0.48

595.00

49.23

0.87

In 2005, the Analytical Chemistry Core began collaborating with Dan Brabander, Assistant Professor of Biogeochemistry in the Geosciences Department at Wellesley College, to examine trace metal concentrations in residential house dust and yard soil, collected as part of the exposure assessment study, using two complimentary X-ray fluorescence spectroscopy (XRF) approaches.  A field-portable (FP)-XRF Niton (NITON XLi 700 Series Environmental Analyzer, Thermo Electron Corporation, Billerica, MA) is being used for in-situ measurements as well as prepared samples, and a Spectra XEPOS (Spectra Analytical, Kleve, Germany) polarized energy dispersive XRF (pED-XRF) instrument will be utilized to analyze a subset of samples.  This additional testing is conducted in accordance with EPA method 6200, which, for quality control purposes, requires that a subset of in-situ FP-XRF samples be analyzed by a complementary analytical method.  Testing of all unknown samples via XRF is bracketed with National Institute of Standards and Technology (NIST) 2709 or NIST 2711 Standard Reference Material.

There also has been preliminary analysis of trace metal contents in house dust by XRF.  All house dust samples are sieved to 125 µm size fraction before they are placed in XRF sample cups with 6 µm thick Mylar film windows.  Because of the low mass yield of house dust per sample (average 0.5 g), there is continual method development and experimentation to yield reproducible, accurate metal concentrations, particularly from the pED-XRF.  Table 3 displays preliminary trace metal concentrations in house dust using the FP-XRF Niton.  Next steps will involve analyzing a subset of house dust samples through acid digestions.

Table 3.  Metal Concentrations in House Dust from Homes in

Tar Creek, Oklahoma Using XRF

 

Lead
(ppm)

Manganese
(ppm)

Zinc
(ppm)

Iron
(ppm)

Copper
(ppm)

Arsenic
(ppm)

Sample Size

40

40

40

 

40

40

40

Minimum

10

LOD

190

940

12

9

Mean

90

110

1100

4900

130

30

Maximum

530

470

4600

22000

1200

70

In 2005, the Chemistry Core developed sampling equipment related to the exposure assessment activities. Low-flow size selective (PM2.5) particle samplers have been 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.

In another effort, the Analytical Chemistry Core has prepared respirable chat for use in animal studies.  We have constructed and tested successfully an apparatus designed to aerosolize Tar Creek chat into unitary airborne particles and then collect the respirable fraction (Figure 1).  The apparatus consists of a 30-gallon electrically grounded, gasketed steel drum with three well-sealed penetrations.  One penetration is used for a grounded ejector—sometimes referred to as an eductor or aspirator—which aerosolizes the chat and then introduces the resulting aerosol into the drum.  Another penetration is used to remove the aerosol from the drum and deliver it to a 15 cfm cyclone (Aerotec 2), which has a 50 percent cut point of 3.5 μm.  This cyclone removes all particles that are nonrespirable.  Respirable particles pass through the cyclone and are collected onto a polypropylene fibrous filter.  The third penetration, which is connected to a HEPA filter, allows excess air to flow into the drum, because the airflow exiting the ejector and entering the drum is less than the 15 cfm exiting the drum.

Figure 1. Respirable Dust Separator

Figure 1.  Respirable Dust Separator

In the ejector, filtered compressed air at about 30 psig flows through a Venturi nozzle at sonic velocity.  Because of the Bernoulli effect, a relatively high vacuum is created in a perpendicular tube connected to the throat of the Venturi through which the chat is manually fed.  The chat previously has been sieved to remove particles larger than 37 μm (400 mesh) and then oven-dried overnight at about 90-95ºC.  (In future tests, the chat will be dried at about 50ºC.)  A considerable amount of energy is expended in the ejector to accelerate the chat to sonic velocity, in the process breaking up aggregates into unitary particles.

The respirable dust collected on the polypropylene fibrous filter is put into a glass container, covered with deionized water, and placed in an ultrasonic bath overnight.  After removing the filter, the water and chat mixture is placed in a 90-95ºC oven until all of the water evaporates.  In future experiments, we plan to remove the water from the chat by freeze drying.
Thus far, we have given 550 mg of respirable chat to Ramon Molina for animal studies and 100 mg to Laurel Schaider for metal analysis.  Her analysis indicated that the respirable chat was 30.7 percent Zn, 2.0 percent Pb, 445 ppm Mn, 400 ppm Cd, and 82 ppm Ni.  We also have another 500 mg respirable chat sample that is available.  At this point in time, we are ready to enter the production phase.  Because the yield is relatively low—about 5 percent of the sieved chat is collected as respirable chat—production may take some time, depending on the amount of respirable chat required.  Marianne Wessling-Resnick needs much larger quantities of respirable chat for her animal studies than Ramon Molina, as much as 12 g of respirable chat per kg of rat exposed.

Core C:  Biostatistics

The Statistics and Data Analysis Core has added data management capabilities.  The staff are involved in designing questionnaires and exposure-related forms supporting Projects 1 and 2 to aid data entry and in designing databases and data management systems.  In addition, we have consulted with Project 2 on issues in the design of the sampling for some of the exposure variables and analysis of the data, and with team members for Project 1 on issues in modeling potentially nonlinear associations that have been used in preliminary analyses of early data from that project.  We have developed a data analysis plan for examining multilevel data with spatial correlation using R software.

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.  Although Project 3 has yielded a number of important scientific insights relevant to routes of metals absorption, they are of yet unclear significance to the general public.  Project 4 is only at an early stage of data collection and has not yielded any significant results for distribution and outreach. The COTC is administered through a subcontract to the 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 the National Institute of Environmental Health Sciences (NIEHS), namely to:  (1) promote active collaboration and participation at the community level; (2) foster colearning between community and researchers; (3) ensure center-sponsored research continues to be community driven; (4) disseminate results in useful language; and (5) ensure the cultural appropriateness of research and intervention strategies.

The CAB includes 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
Flossie Mathews—Quapaw Tribe
Paul Barton—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 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.  

The COTC manages the CAB meetings, coordinating with the CoChair, Kathy Ellis.  In Year 2 of the grant, , the CAB met two times:  April 11 and August 8, 2005.  Topics for discussion included membership, meeting schedule and times, updates on research projects, and review of recent COTC work products.  The CAB also approved an ethics statement.  Dr. Howard Hu participated in the meetings by telephone.  Adrienne Ettinger, a researcher on Project 1, attended the April meeting.  Ami Zota, a researcher on Projects 1 and 2 attended and presented at the August meeting.

Specific Aim 1:  Compile and Summarize Information From the Literature and From the Findings of the Center-Sponsored Studies and Make Documents Available in the Public Library Tar Creek Repository.As the Center-sponsored studies continue, more information will be available to share with the community.  Copies of the L.E.A.D. Agency newsletter (discussed below) with articles about the Children’s Center are available at the Tar Creek Repository.  News articles are posted on the L.E.A.D. Agency Web Site (http://www.leadagency.org) as well as sent as e-mails to the established lists.  Articles are added to the library that was set up at the COTC office this year.  The COTC is continuing to collaborate with teachers from area schools and colleges on ways to have more student involvement in making the research information interesting to youths and the community.

During a visit to Tar Creek in November, Ann Backus visited the Repository with Rebecca Jim. The area is accessible through library staff and houses EPA documents pertaining to the Tar Creek Superfund Site, a variety of independent studies, and newsletters from the COTC.  Future additions to the Repository will include journal articles by the researchers.

Specific Aim 2:  Develop and Publicize Simple Measures for Assessing and Mitigating Risks of Exposures to Pregnant Women and Children.  The Children’s Center Updates published in April, June, and December contained articles on the Children’s Center, COTC, the CAB, the Tribal Subcommittee, and the work with youth.  The December issue included the news coverage of Dr. David Bellinger’s presentation on his research on the relationship of levels of heavy metals (As, Mn, Cd, and Pb) in the hair of fifth and sixth graders in Miami district schools to a variety of cognitive, problem-solving tests.  This pilot study showed an inverse relationship between the combination of As and Mn exposure and verbal intelligence.  As mentioned above, copies of the updates are available in the Miami Public Library, Tar Creek Repository.  They also were mailed to the L.E.A.D. Agency mailing list.

A message sign, located outside the COTC office is used to issue simple reminders to passersby regarding housecleaning, fish warnings, and having their children’s lead levels checked.

A youth activity booklet was developed that includes information about the health, history, and culture of the area.

A poster for doctor’s offices is being developed.  Books donated by one of the Children’s Center scientists are being given to children and their families with simple messages on bookmarks at the MATCH office, the County Health Department, Department of Human Services, Indian clinic, and other public places.

Specific Aim 3:  Use COTC Web Site to Communicate Progress in Each of the Children’s Center’s Research Projects.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, 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.  A community member developed a Web site featuring her classwork at Northeastern Oklahoma A&M College on drinking water quality, which includes a geographic information system (GIS) component for locating various drinking water sources.  Her Web site is now linked to the L.E.A.D. Agency Web Site.

Specific Aim 4:  Arrange for and Sponsor the Participation of Center Faculty in Teaching Environmental Health Concepts.Rebecca Jim and Earl Hatley have continued discussions with NEO personnel regarding how to proceed with distance learning.  Ann Backus continues to create the mechanisms to bring Howard Hu’s lectures in the course, “Principles of Environmental Health” and also Grand Rounds available for community use.  Future topics include:  Dr. David Bellinger, Children’s Hospital Boston:  Importance of Pilot Studies; Dr. Robert Wright, HSPH:  MATCH Project Update; and Dr. Brian Fligor, Children’s Hospital Boston:  Objective Hearing Tests and Metals Exposures.

Sarah Putney, the Executive Director of the Human Subjects Committee at the HSPH, visited Miami, Oklahoma, and met with available CAB and community members about the Institutional Review Board process at HSPH.  She is the featured interview in the latest Children’s Center newsletter.

The Miami Tribe has donated the equipment to create a Distance Learning Laboratory in the COTC office and will provide the training to operate it.  The tribe donated similar equipment to all of the area schools, so many of the Center scientists will find it easy to share presentations with youth and the community next year.  The first step was arranging for the faster Internet service that the distance learning equipment required; installation was completed in December.  Tapes of the presentations can be made at each station for future use.

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.  A volunteer interested in helping to write the modules has been identified.

Specific Aim 6:  Sponsor a Community Scholars Program.  Several potential community scholars and projects have been identified.  The first meeting with six potential Local Scholars was held in November with Ann Backus, Earl Hatley, and Rebecca Jim.  Formal applications for the program are being collected, and then the six will be the initial cohort of scholars.  Ann Backus will be assigning Harvard faculty or other professionals, such as professional photographers, depending on the nature of their projects, as mentors to the Local Scholars.  Examples or topics of proposed projects include:  Youth Tobacco Use, Water Quality and Safety of Swimming in Sinkholes, Local Scholar Photography, GIS, Aquatic Life in Tar Creek Over Time, and Tribal Culture.

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 was held on May 5-6, 2005 at the Miami Civic Center, Miami, Oklahoma.  The 2-day conference involved community members in the planning and community and tribal support with youth volunteers.

Additional Comments

  • Ann Backus and Gail Fleischaker created procedures and forms that simplify the administrative management for the COTC during a site visit to Miami in November 2005.
  • Vaughn Wascovich, Harvard Visiting Scholar, serving as one of the Tar Creek photographers donated 20 large color images that will be viewed in a series of shows.  Nancy Goldenberg, a former resident, studied photography and donated a set of 12 framed and matted photos that were Vaughn’s inspiration to come to Tar Creek.  This set is hanging in the COTC office.
  • COTC staff and community members attended a training for the portable XRF and an 8-hour training entitled, “Addressing Lead-Based Paint Hazards During Renovation, Remodeling and Rehabilitation in Federally Owned and Assisted Housing.”
  • Oral Roberts University students checked the blood pressure of and determined a body mass index for individuals through the use of a scale donated to the COTC office by one of the CAB Co-Chairs during two fundraisers for the Local Scholars’ Projects.

Conclusion. The accomplishments included the first Tar Creek Conference, in which a number of the Children’s Center scientists were involved.  The CAB and the Tribal Subcommittee assumed their roles as advisors for the Children’s Center.  Also during Year 2, the Center continued to publish a newsletter and to maintain the Web sites, improved the office space, increased the visibility of the Children’s Center at Tar Creek, and created events that interest the community.  Collaboration between tribes, the community, and the researchers for this community-based research in the field of children’s environmental health continues.  We are grateful for everyone’s contributions to 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)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
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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)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
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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)
    R831725 (2009)
    R831725C001 (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)
    R831725C001 (2008)
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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)
    R831725 (2009)
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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)
    R831725C001 (2005)
    R829389 (2003)
    R829389 (2004)
    R829389 (2005)
    R829389 (Final)
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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)
    R831725 (2009)
    R831725C001 (2005)
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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)
    R831725 (2009)
    R831725C001 (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)
    R831725 (2009)
    R831725C001 (2007)
    R831725C001 (2008)
    R831725C003 (2007)
    R831725C004 (2007)
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  • Abstract from PubMed
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  • Other: ScienceDirect-Full Text PDF
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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)
    R831725 (2009)
    R835441 (2017)
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  • Abstract: Pediatrics-Abstract
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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)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
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  • Full-text: Journal of Nutrition-Full Text HTML
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  • Other: Journal of Nutrition-PDF
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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)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
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  • Other: ScienceDirect-Full Text PDF
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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)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
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  • Abstract: FASEB-Abstract
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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)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: AJPGI-Full Text HTML
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  • Other: AJPGI-Full Text PDF
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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)
  • Abstract from PubMed
  • 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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  • Journal Article Wright RO, Fields N. Therapeutics and toxicology. Current Opinion in Pediatrics 2008;20(2):171. R831725 (2009)
    R831725C001 (2008)
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  • 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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  • 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)
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  • 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)
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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
  • 2004 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