2004 Progress Report: Center for Childhood Neurotoxicology and Assessment

EPA Grant Number: R829391
Center: CECEHDPR - University of Medicine and Dentistry of New Jersey Center for Childhood Neurotoxicology and Assessment
Center Director: Lambert, George H.
Title: Center for Childhood Neurotoxicology and Assessment
Investigators: Lambert, George H. , Lu, Shou-En , Reuhl, Kenneth R. , Spencer, Stephanie
Current Investigators: Lambert, George H.
Institution: University of Medicine and Dentistry of New Jersey
EPA Project Officer: Louie, Nica
Project Period: November 1, 2001 through October 31, 2006
Project Period Covered by this Report: November 1, 2003 through October 31, 2004
Project Amount: $6,751,466
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health

Objective:

The unifying theme of the Center for Childhood Neurotoxicology and Assessment is to determine the influence of exposure to neurotoxicants on child neurological health and development, with autism and related learning disabilities as a focus. The objectives of the Center are to detect, understand, and prevent environmental health problems as they relate to children. These objectives are achieved by facilitating interdisciplinary research, enhancing community and advocacy group involvement, and disseminating results to the public through publications, conferences, and community outreach.

The multidisciplinary research of the Center is based on three main project areas. The Basic Sciences Projects examine facets of brain development, beginning with neurogenesis and proceeding through to behavior in the intact animal. The Clinical Sciences Projects are interactive with community groups representing children with learning disabilities and their families, with particular emphasis on autism. These projects explore the linkage between environmental neurotoxicants, clinical course of autism, regional brain growth, and a possible new gene-environment interaction with autism. The Exposure Assessment and Intervention Project (EAIP) will characterize the personal, residential, and general community of exposure of children selected by the Clinical Sciences Projects. The EAIP then will determine the need for interventions to reduce neurotoxicant exposure among learning-disabled children and assess the impact of such interventions. The Exposure Assessment Facility Core will provide innovative video techniques to assess the relationship between the behavior of the child with autism and his/her potential to contact with neurotoxicants. The overall mission of the Center is to improve environmental and public health of children through research, assessment, treatment, and outreach.

Progress Summary:

The National Institute of Environmental Health Sciences (NIEHS)/U.S. Environmental Protection Agency (EPA) Center for Childhood Neurotoxicology and Exposure Assessment has completed the first 3 years of the grant. The Center is assuming a prominent position in the environmental and autism communities of New Jersey and regionally.

The Center’s research is progressing well and has been a very positive force in the academic and lay communities. The Center has attracted additional researchers into studying the relationships between environmental chemicals and autism.

The Center was developed in conjunction with the community, and community involvement has increased through lectures, newspaper articles, and the addition of community members involved in the research. The Center has had extensive opportunities to discuss and instruct the general community and, in particular the autism community, about the concerns of environmental chemicals on child development. This risk communication has been done in a frank and careful discussion of the literature, describing what is known, not known, and what needs further research. It also describes how to decrease children’s exposure to environmental chemicals. The community has appreciated the Center’s role in this effort. The Center also has taken a lead in providing information to Congress on issues effecting children’s environmental health.

The Center has been acknowledged by the Center’s members in 16 published articles and more than 16 abstracts in the first 3 years. The members have been active participants and leaders in many research conferences, both locally and nationally. The Center members have applied to the National Institutes of Health (NIH) for additional grants that will expand greatly the capacity of the Center. These grants build the Center’s capacity by including additional child cohorts (Dr. Shalat’s Mexican Border population and Dr. Lambert’s studies in Taiwan), a new Pediatric Clinical Research Center with emphasis on environmental studies, and additional basic science efforts.

Scientific and Community Outreach Meetings

The Center has been active in outreach to the scientific and lay community. The major Center meeting was held in conjunction with NIEHS and the University of California at Davis (UC-Davis) Children’s Environmental Health Center. The meeting “Autism, Genes and The Environment” was held October 3-4, 2003, in New Jersey, and drew 199 scientists from almost all the major universities in the Northeast and more than 100 parents from as far away as Hawaii. The meeting successfully reframed the questions of autism and the environment. This meeting will be held on an annual basis, rotated between the New Jersey Center and the California Children’s Center as lead institution. The next meeting will be held in the spring of 2004 as a satellite of the International Meeting for Autism Research (IMFAR) to be held at the University of California.

The Center also is planning a National Town Meeting for Children during the week of Earth Day 2004. The primary goals of the meeting are to: (1) explore with the children the state of their environment and what they can do to improve it; and (2) identify environmental science careers and what education is needed to enter these fields. The NIEHS, EPA, U.S. Geological Survey, Centers for Disease Control and Prevention, National Aeronautics and Space Administration, and the Chemistry Council all have agreed to participate. The next planning meeting will be held in August in Washington, DC, with all of the agencies participating.

The Center also is working with the UC-Davis Center in helping to organize a component of the University of Arkansas’ Annual Neurotoxicology meeting being held in Hawaii, in February 2004. The two NIEHS/EPA Centers are organizing one session featuring research from the 12 NIEHS/EPA Children’s Centers and another one on autism, possibly in a town meeting format. The Center continues to attend many local community autism meetings in New Jersey to present the issues of children and the environment with childhood autism as the focus. Dr. Lambert was privileged make a presentation at the NIEHS Children’s Environmental Health Symposium in Bethesda, Maryland, this past winter and at several of the NIEHS meetings held at both Yale University and EPA in Research Triangle Park, North Carolina.

Congressional Outreach

The Center has taken on a role of educating Congress on children’s environmental health issues. Dr. Lambert participated in a senate briefing (sponsored by Senators Kennedy, Reed, and Clinton and Physicians for Social Responsibility) on health disease tracking for environmental linkage. Dr. Lambert discussed autism and the environment. This was a highly successful meeting. Dr. Lambert just recently has obtained agreement from Senator Corzine (D-NJ) and Representative Chris Smith’s (R-NJ) Office to be the lead cosponsors of an annual congressional briefing on children’s environmental health. The first one is being planned for late winter or early spring 2005.

Message of the Center’s Director

A main message of the Center is that children with neurological dysfunction (as represented by children with autism) are at risk from environmental chemicals. In fact, they may be at greater risk because of their local environment (older schools, etc.), behavior (mouthing, etc.), end organ susceptibility, and the effects of environmental chemicals on the children’s capacity to function. Despite this, there has been very little effort to study the effects of environmental chemicals on these most susceptible children. The Center’s Basic and Clinical research is addressing these issues in a collaborative/interactive effort. The Center has reached out to the community to inform them of the issues and needs to reduce exposure of these children to environmental chemicals and methods that parents can use to reduce children’s exposure.

Future Activities:

The researchers did not report any future activities.


Journal Articles: 49 Displayed | Download in RIS Format

Other center views: All 86 publications 50 publications in selected types All 49 journal articles
Type Citation Sub Project Document Sources
Journal Article Akland GG, Pellizzari ED, Hu Y, Roberds M, Rohrer CA, Leckie JO, Berry MR. Factors influencing total dietary exposures of young children. Journal of Exposure Analysis and Environmental Epidemiology 2000;10(6 Pt 2):710-722. R829391 (2004)
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  • Journal Article Ayotte P, Dewailly E, Lambert GH, Perkins SL, Poon R, Feeley M, Larochelle C, Pereg D. Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines. Environmental Health Perspectives 2005;113(10):1318-1324. R829391 (2004)
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  • Journal Article Benayed R, Gharani N, Rossman I, Mancuso V, Lazar G, Kamdar S, Bruse SE, Tischfield S, Smith BJ, Zimmerman RA, DiCicco-Bloom E, Brzustowicz LM, Millonig JH. Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus. American Journal of Human Genetics 2005;77(5):851-868. R829391 (2004)
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  • Journal Article Black K, Shalat SL, Freeman NCG, Jimenez M, Donnelly KC, Calvin JA. Children's mouthing and food-handling behavior in an agricultural community on the US/Mexico border. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(3):244-251. R829391 (2004)
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  • Journal Article Brenz Verca MS, Bahi A, Boyer F, Wagner GC, Dreyer J-L. Distribution of α- and γ-synucleins in the adult rat brain and their modification by high-dose cocaine treatment. European Journal of Neuroscience 2003;18(7):1923-1938. R829391 (2004)
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  • Journal Article Burke K, Cheng Y, Li B, Petrov A, Joshi P, Berman RF, Reuhl KR, DiCicco-Bloom E. Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E. NeuroToxicology 2006;27(6):970-981. R829391 (2006)
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  • Journal Article Buyske S, Williams TA, Mars AE, Stenroos ES, Ming SX, Wang R, Sreenath M, Factura MF, Reddy C, Lambert GH, Johnson WG. Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genetics 2006;7(1):8 (9 pp.). R829391 (2006)
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  • Journal Article Calafat AM, Needham LL, Silva MJ, Lambert G. Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. Pediatrics 2004;113(5):e429-e434. R829391 (2004)
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  • Journal Article Carlson KM, Wagner GC. Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum. Life Sciences 2005;77(4):372-385. R829391 (2004)
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  • Journal Article Carmody DP, Dunn SM, Boddie-Willis AS, DeMarco JK, Lewis M. A quantitative measure of myelination development in infants, using MR images. Neuroradiology 2004;46(9):781-786. R829391 (2004)
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  • Journal Article Carmody DP, Moreno R, Mars AE, Seshadri K, Lambert GH, Lewis M. Brief report: brain activation to social words in a sedated child with autism. Journal of Autism and Developmental Disorders 2007;37(7):1381-1385. R829391 (2006)
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  • Journal Article Cheh MA, Millonig JH, Roselli LM, Ming X, Jacobsen E, Kamdar S, Wagner GC. En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder. Brain Research 2006;1116(1):166-176. R829391 (2006)
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  • Journal Article Chen T-F, Zhang Y-L, Xu W-L, Li Z-Q, Hou B, Wang C-L, Fan M, Qian L-J, Zhou R-P, Zhang C-G. Prokaryotic expression, polyclonal antibody preparation, and sub-cellular localization analysis of Na+, K+-ATPase β2 subunit. Protein Expression and Purification 2004;37(1):47-52. R829391 (2004)
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  • Journal Article Chen Z-Y, Sun C, Reuhl K, Bergemann A, Henkemeyer M, Zhou R. Abnormal hippocampal axon bundling in EphB receptor mutant mice. Journal of Neuroscience 2004;24(10):2366-2374. R829391 (2004)
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  • Journal Article Davidovics Z, DiCicco-Bloom E. Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture. Journal of Neuroscience Research 2005;80(6):817-825. R829391 (2004)
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  • Journal Article Falluel-Morel A, Sokolowski K, Sisti HM, Zhou X, Shors TJ, Dicicco-Bloom E. Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty. Journal of Neurochemistry 2007;103(5):1968-1981. R829391 (2006)
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  • Journal Article Fitzgerald EF, Hwang SA, Lambert G, Gomez M, Tarbell A. PCB exposure and in vivo CYP1A2 activity among Native Americans. Environmental Health Perspectives 2005;113(3):272-277. R829391 (2004)
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  • Journal Article Freeman NCG, Jimenez M, Reed KJ, Gurunathan S, Edwards RD, Roy A, Adgate JL, Pellizzari ED, Quackenboss J, Sexton K, Lioy PJ. Quantitative analysis of children's microactivity patterns: the Minnesota Children's Pesticide Exposure Study. Journal of Exposure Analysis and Environmental Epidemiology 2001;11(6):501-509. R829391 (2004)
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  • Journal Article Freeman NCG, Sheldon L, Jimenez M, Melnyk L, Pellizzari E, Berry M. Contribution of children's activities to lead contamination of food. Journal of Exposure Analysis and Environmental Epidemiology 2001;11(5):407-413. R829391 (2004)
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  • Journal Article Freeman NCG, Shalat SL, Black K, Jimenez M, Donnelly KC, Calvin A, Ramirez J. Seasonal pesticide use in a rural community on the U.S./Mexico border. Journal of Exposure Analysis and Environmental Epidemiology 2004;14(6):473-478. R829391 (2004)
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  • Journal Article Georgopoulos PG, Lioy PJ. From a theoretical framework of human exposure and dose assessment to computational system implementation: the Modeling ENvironment for TOtal Risk Studies (MENTOR). Journal of Toxicology and Environmental Health, Part B-Critical Reviews 2006;9(6):457-483. R829391 (2006)
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  • Journal Article Halladay AK, Kusnecov A, Michna L, Kita T, Hara C, Wagner GC. Relationship between methamphetamine-induced dopamine release, hyperthermia, self-injurious behaviour and long term dopamine depletion in BALB/c and C57BL/6 mice. Pharmacology & Toxicology 2003;93(1):33-41. R829391 (2004)
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  • Journal Article Halladay AK, Tessarollo L, Zhou R, Wagner GC. Neurochemical and behavioral deficits consequent to expression of a dominant negative EphA5 receptor. Molecular Brain Research 2004;123(1-2):104-111. R829391 (2004)
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  • Journal Article Halladay AK, Wagner GC, Sekowski A, Rothman RB, Baumann MH, Fisher H. Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan. Synapse 2006;59(5):277-289. R829391 (2005)
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  • Journal Article Halladay AK, Wilson DT, Wagner GC, Reuhl KR. Trimethyltin-induced alterations in behavior are linked to changes in PSA-NCAM expression. NeuroToxicology 2006;27(2):137-146. R829391 (2004)
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  • Journal Article Hsu PC, Lai TJ, Guo NW, Lambert GH, Leon Guo Y. Serum hormones in boys prenatally exposed to polychlorinated biphenyls and dibenzofurans. Journal of Toxicology and Environmental Health-Part A 2005;68(17-18):1447-1456. R829391 (2006)
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  • Journal Article Hsu P-C, Huang W, Yao W-J, Wu M-H, Guo YL, Lambert GH. Sperm changes in men exposed to polychlorinated biphenyls and dibenzofurans. Journal of the American Medical Association 2003;289(22):2943-2944. R829391 (2004)
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  • Journal Article Hu Z, Yue X, Shi G, Yue Y, Crockett DP, Blair-Flynn J, Reuhl K, Tessarollo L, Zhou R. Corpus callosum deficiency in transgenic mice expressing a truncated ephrin-A receptor. Journal of Neuroscience 2003;23(34):10963-10970. R829391 (2004)
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  • Journal Article Hu Z, Cooper M, Crockett DP, Zhou R. Differentiation of the midbrain dopaminergic pathways during mouse development. Journal of Comparative Neurology 2004;476(3):301-311. R829391 (2004)
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  • Journal Article Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito PA, Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S. Community-based participatory research:lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1463-1471. R829391 (2004)
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  • Journal Article Johnson SK, Carlson KM, Lee J, Burr LE, Wagner GC. Effects of nicotine on target biting and resident-intruder attack. Life Sciences 2003;73(3):311-317. R829391 (2006)
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  • Journal Article Johnson WG, Scholl TO, Spychala JR, Buyske S, Stenroos ES, Chen X. Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery. American Journal of Clinical Nutrition 2005;81(3):664-668. R829391 (2004)
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  • Journal Article Kita T, Wagner GC, Nakashima T. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption. Journal of Pharmacological Sciences 2003;92(3):178-195. R829391 (2004)
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  • Journal Article Lioy PJ, Freeman NC, Millette JR. Dust: a metric for use in residential and building exposure assessment and source characterization. Environmental Health Perspectives 2002;110(10):969-983. R829391 (2006)
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  • Journal Article Lioy PJ. Employing dynamical and chemical processes for contaminant mixtures outdoors to the indoor environment: the implications for total human exposure analysis and prevention. Journal of Exposure Science & Environmental Epidemiology 2006;16(3):207-224. R829391 (2004)
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  • Journal Article Martin JV, Nolan B, Wagner GC, Fisher H. Effects of dietary caffeine and alcohol on liver carbohydrate and fat metabolism in rats. Medical Science Monitor 2004;10(12):BR455-BR461. R829391 (2006)
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  • Journal Article Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins, Leukotrienes and Essential Fatty Acids 2005;73(5):379-384. R829391 (2004)
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  • Journal Article Prozialeck WC, Grunwald GB, Dey PM, Reuhl KR, Parrish AR. Cadherins and NCAM as potential targets in metal toxicity. Toxicology and Applied Pharmacology 2002;182(3):255-265. R829391 (2004)
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  • Journal Article Shalat SL, Donnelly KC, Freeman NCG, Calvin JA, Ramesh S, Jimenez M, Black K, Coutinho C, Needham LL, Barr DB, Ramirez J. Nondietary ingestion of pesticides by children in an agricultural community on the U.S./Mexico border: preliminary results. Journal of Exposure Analysis and Environmental Epidemiology 2003;13(1):42-50. R829391 (2004)
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  • Journal Article Turan VK, Sanchez RI, Li JJ, Li SA, Reuhl KR, Thomas PE, Conney AH, Gallo MA, Kauffman FC, Mesia-Vela S. The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17β-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16α-hydroxyestradiol, and 4-hydroxyestrone. Journal of Endocrinology 2004;183(1):91-99. R829391 (2006)
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  • Journal Article Wagner GC, Avena N, Kita T, Nakashima T, Fisher H, Halladay AK. Risperidone reduction of amphetamine-induced self-injurious behavior in mice. Neuropharmacology 2004;46(5):700-708. R829391 (2004)
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  • Journal Article Wagner GC, Reuhl KR, Cheh M, McRae P, Halladay AK. A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. Journal of Autism and Developmental Disorders 2006;36(6):779-793. R829391 (2004)
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  • Journal Article Wagner GC, Reuhl KR, Ming X, Halladay AK. Behavioral and neurochemical sensitization to amphetamine following early postnatal administration of methylmercury (MeHg). NeuroToxicology 2007;28(1):59-66. R829391 (2006)
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  • Journal Article Williams TA, Mars AE, Buyske SG, Stenroos ES, Wang R, Factura-Santiago MF, Lambert GH, Johnson WG. Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Archives of Pediatric Adolescent Medicine 2007;161(4):356-361. R829391 (2006)
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  • Journal Article Wilson DT, Polunas MA, Zhou R, Halladay AK, Lowndes HE, Reuhl KR. Methylmercury alters Eph and ephrin expression during neuronal differentiation of P19 embryonal carcinoma cells. NeuroToxicology 2005;26(4):661-674. R829391 (2004)
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  • Journal Article Yang C-Y, Yu M-L, Guo H-R, Lai T-J, Hsu C-C, Lambert G, Guo YL. The endocrine and reproductive function of the female Yucheng adolescents prenatally exposed to PCBs/PCDFs. Chemosphere 2005;61(3):355-360. R829391 (2004)
    R829391 (2005)
    R829391 (2006)
    R829391C005 (2006)
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  • Journal Article Ye X, Fitzgerald EF, Gomez MI, Lambert GH, Longnecker MP. The ratio of specific polychlorinated biphenyls as a surrogate biomarker of cytochrome P4501A2 activity--a pharmaco-metabonomic study in humans. Cancer Epidemiology Biomarkers & Prevention 2008;17(4):1013-1025. R829391 (2006)
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  • Journal Article Yu CH, Yiin LM, Lioy PJ. The bioaccessibility of lead (Pb) from vacuumed house dust on carpets in urban residences. Risk Analysis 2006;26(1):125-134. R829391 (2006)
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  • Journal Article Zhang C, Meng F, Wang C, Guo H, Fan M, Liu S, Zhou R, He F. Identification of a novel alternative splicing form of human netrin-4 and analyzing the expression patterns in adult rat brain. Molecular Brain Research 2004;130(1-2):68-80. R829391 (2004)
    R829391 (2005)
    R829391 (2006)
    R829391C002 (2006)
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  • Supplemental Keywords:

    children’s health, disease and cumulative effects, ecological risk assessment, environmental chemistry, health risk assessment, susceptibility, sensitive population, genetic susceptibility, toxicology, assessment of exposure, assessment technology, autism, behavioral assessment, behavioral deficits, childhood learning, developmental disorders, developmental effects, environmental health hazard, environmental toxicant, exposure assessment, gene-environment interaction, neurodevelopmental, neurological development, neuropathological damage, neurotoxic, neurotoxicity, outreach and education, public health,, RFA, Health, Scientific Discipline, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Children's Health, genetic susceptability, Ecological Risk Assessment, Biology, childhood learning, neurotoxic, gene-environment interaction, developmental effects, behavioral assessment, children, neurodevelopmental, neurotoxicity, public health, residential populations, behavioral deficits, assessment of exposure, autism, environmental toxicant, environmental health hazard, outreach and education, assessment technology, developmental disorders, exposure assessment, neurological development

    Progress and Final Reports:

    Original Abstract
  • 2002
  • 2003
  • 2005 Progress Report
  • Final
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R829391C001 Neurotoxicant Effects on Cell Cycle Regulation of Neurogenesis
    R829391C002 Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury
    R829391C003 Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills
    R829391C004 Exposure Assessment and Intervention Project (EAIP)
    R829391C005 Clinical Sciences Project