![[logo] US EPA](https://webarchive.library.unt.edu/eot2008/20081105121523im_/http://www.epa.gov/epafiles/images/logo_epaseal.gif){kind=logo}
2000 Progress Report: Center for Child Environmental Health Risks Research
EPA Grant Number: R826886Center: University of Washington
Center Director: Faustman, Elaine
Title: Center for Child Environmental Health Risks Research
Investigators: Faustman, Elaine
Institution: University of Washington
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through December 31, 2003
Project Period Covered by this Report: August 1, 1999 through July 31,2000
Project Amount: $3,545,396
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects
Description:
Objective:Neurobehavioral Assessment Core
Goals and Specific Aims. The overall goals of this research core are to: (1) conduct studies aimed at defining the effects of early pesticide exposure on neurobehavioral development; and (2) utilize the results of these studies as a basis for integrating behavioral and mechanistic approaches for defining the dose-response characteristics of effects due to early pesticide exposure.
The specific aims of this research core are to: (1) evaluate the role of paraoxonase polymorphism in defining the susceptibility to the neurobehavioral effects of postnatal organophosphorus (OP) insecticide exposure; (2) determine the concentration-dependent relationship between prenatal exposure to pesticides and alterations in neurobehavioral development; and (3) correlate these neurobehavioral effects with observed alterations in cell cycle progression.
Exposure Assessment Core
Four specific aims were identified for the Exposure Core in the original proposal: (1) provide analytical chemical support to the intervention project, (2) manage an exploratory arsenic exposure supplement to the field projects, (3) coordinate mechanistic modeling of exposure and dose among all center projects, and (4) provide exposure modeling support to the Pathways Project.
Risk Characterization Core
The specific aims of this core project have not changed, they are to: (1) provide statistical collaboration and consultation on study design and data analysis; (2) develop new methods for study evaluation; (3) develop and characterize new risk assessment methods that specifically improve models used for assessing children’s environmental risks; and (4) collaborate in the writing of manuscripts.
Risk Communication Core
The goal of the Risk Communication Core is to provide a critical link between Center researchers and the regional and national community on issues of environmental impacts to children’s health. The specific aims of the Risk Communication Core include: (1) working with our community partners in our field-based projects; (2) developing, with our national scientific colleagues and health professionals, a library of materials relevant to understanding the potential impacts from the environment on children’s health; (3) developing continuing education courses for regional health, safety, and regulatory professionals on child health; and (4) disseminating research findings and making a difference for risk assessment for children.
Administrative Core
The Administrative Core is responsible for oversight, coordination, and management of the scientific and administrative aspects of the University of Washington Center for Child Environmental Health Risks Research (CHC). The Administrative Core also facilitates communication with our funding agencies, other Children’s Centers, and interested individuals and organizations. Center Director, Dr. Elaine Faustman, is assisted by two Deputy Directors, Dr. Thomas Burbacher (Associate Professor, Department of Environmental Health) and Dr. Richard Fenske (Professor and Director, Pacific Northwest Agricultural Safety and Health Center, Department of Environmental Health); Ms. Ruth Woods (Program Administrator); Ms. Tiffany Potter-Chiles (Program Coordinator), and Ms. Donna Prisbrey (Program Assistant).
Progress Summary:Neurobehavioral Assessment Core
During the second year of the Center grant, we successfully advertised and hired a Research Scientist to direct the core research activities. Dr. Kristina Dam was hired as of July 1, 2000. Dr. Dam has extensive experience in the area of pesticide developmental neurotoxicity. Her initial efforts thus far have been directed at developing the design for the behavioral studies for the Pon1-knockout mice. It was decided, in collaboration with our external advisory committee, that the knockout mice studies should be prioritized using both postnatal and prenatal exposure models. We were able to exchange some of the equipment that we had ordered for testing rats as well as purchase new equipment for mice to accommodate these studies. Equipment is on hand for assessing spontaneous motor activity (The Open Field) and learning and memory (The Radial Arm Maze and the Morris Maze). This equipment utilizes the Poly-Track Video Tracking System (San Diego Instruments), which automates the collection and summary of the data. Additional equipment is being ordered to provide testing capabilities for acoustic startle response and operant testing. Dr. Dam will continue to work with Drs. Burbacher, Furlong, and Costa during the next couple of months to finalize the design for the paraoxonase studies and begin testing.
Significance. The results of the behavioral studies will provide critical data for the evaluation of the functional consequences of the changes observed in initial molecular mechanism and paraoxonase studies. The data from the behavioral core, integrated with the results from these studies, will provide the basis for biologically based risk models. These models will utilize the results to provide a better understanding how to extrapolate across doses and species for molecular and functional effects of pesticides.
Exposure Assessment Core
Specific Aim 1—Provide Analytical Chemical Support to the Intervention Project. The primary activity of the Exposure Core in Years 1 and 2 has been support of the Community Intervention Project (CIP; R826886C003). Analyses have been completed for adult and child urine samples and house and vehicle dust samples. CIP personnel gathered samples from 219 households. Because sufficient sample mass was not obtained in every case, sample totals are ≤ 219 for individual sample types. Adult and child urine samples were analyzed for five OP metabolites (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, and diethylthiophosphate). House and vehicle dusts were analyzed for six parent compounds (chlorpyrifos, diazinon, azinphos-methyl, malathion, parathion, and phosmet). No difference between CIP communities designated “intervention” and “control” with respect to urinary metabolites (diethyl or dimethyl OP) in adults or children was found.
Specific Aim 2—Manage an Exploratory Arsenic Exposure Supplement to the Field Projects. Limited Exposure Core funds were expended for lead and arsenic analyses of samples from 28 CIP households. House and vehicle dust samples were analyzed for arsenic and lead. Child urine samples were analyzed for speciated arsenic. Households were targeted based on location in communities most likely to have been affected by historical lead arsenate use and availability of samples in excess of primary CIP needs. Results of these and additional analyses funded by other means do not support use of urinary arsenic as a marker of children’s exposure to soils treated historically with lead arsenate.
Specific Aim 3—Coordinate Mechanistic Modeling of Exposure and Dose Among All Center Projects. The physiologic model framework created in Simusolv has been translated and validated into a newer modeling system: SAAM II. This will allow us to use Bayesian parameter fitting and examine Akaike and Bayesian information criteria as measures of fit. We have established an objective model goodness-of-fit test, which will allow us to decide if each of the pesticide-specific physiologic models accurately describes a given data set. An oral route of exposure has been built into the models to account for dust and pica ingestion exposure sources. Automatic calculations of systemic clearance, volume of distribution, and half-life have been built into the models to relate model output to physiologic characteristics (such as adiposity and glomerular filtration rate) and to compare the results of our studies with those previously published. In preparation for an analysis of how child age, body weight, adiposity, gender, and paraoxygenase genotype affect pesticide kinetics, we have conducted similar analyses for toluene and xylenes. L. Wilder, a Ph.D. student in the University of Washington (UW) Department of Environmental Health, and A. Hirabayashi, an undergraduate student, are beginning independent study projects to further develop the physiologic pesticide models.
Specific Aim 4—Provide Exposure Modeling Support to the Pathways Project. An effort to reconcile OP pesticide metabolites measured in urine with OP pesticide exposures predicted on the basis of environmental is ongoing (see Editor’s note in view markup). Activity will be increased now that CIP laboratory analyses are completed and new data are available. Support of the Pathways Project will also include expansion of existing Exposure Core GIS capability to assist with GPS tracking methodology development.
Significance. A key emphasis of the CHC is understanding children’s unique exposure risks. This Core provides necessary computer modeling and analytical chemical support to specific basic research projects.
Completion of a Master’s thesis drawn almost exclusively from the results of the CIP baseline sampling is anticipated in August 2000. A related conference presentation has been accepted for the annual meeting of the International Society of Exposure Analysis in October 2000. Two journal articles are in preparation. A second M.S. thesis will incorporate the arsenic and lead results.
Risk Characterization Core
During the second year significant progress was made in addressing Specific Aims 1 and 2, providing statistical advice on study design, analyzing data, and developing methods to analyze and understand data being produced in the research projects of this grant. These have included coordinating the analysis of data on urinary metabolites for children and adults and pesticide levels in house dust and in car dust and also in the planning of the intervention study to evaluate the effectiveness of community education (Pesticide Exposure Pathways, Exposure Assessment Core and the CIPs). Progress on Specific Aim 3 has resulted in the expansion of Biologically Based Dose Response (BBDR) models for a spectrum of events occurring in neuronal development in the embryonic and fetal brain (Molecular Mechanisms Study). Relevant to Specific Aim 4, Dr. Griffith has been consulting with several graduate students that are currently writing their thesis related manuscripts.
Specific Aims 1 and 2. The risk assessment core is coordinating the analysis of data on urinary metabolites for children and adults and pesticide levels in house dust and car dust and also in the planning of the intervention study to evaluate the effectiveness of community education. The data on urinary metabolites and dust concentrations of pesticides are the endpoints that will be used to evaluate the effectiveness of community education by comparing communities who received a community education program with those which did not receive one. Key statistical issues were addressed in pairing communities based on size and demographics to eliminate the possible effect of these variables in testing whether the intervention of the education program has had an effect on exposure of children. At this time baseline data are available on the urinary metabolites and dust samples for all communities (before the start of the education programs). In addition, demographic data are available from questionnaires used in the selection of eligible homes in the communities and includes information such as income, ethnicity, education of parents, and ages of household members. This information will be used in the intervention analysis and for describing the demographics of farm workers in eastern Washington.
Because we are focusing on environmentally relevant and potentially low levels of pesticide exposure, new statistical methods were developed to analyze the urinary metabolite data. These methods were developed to account for the large fraction of samples below the detection level in the chemical analyses. The chemical analyses were for five different types of metabolites, each of which can come from the metabolism of several pesticides. Three of the metabolites are summed because they result from metabolism of pesticides with dimethyl groups, and the other two are summed because they are metabolites of pesticides with a methyl group. Each metabolite has a different detection level, and for four metabolites many samples were below the detection level. This mixture of detection levels with different fractions of the samples below the detection level for each metabolite required the development of new statistical methods.
Often when samples are below a chemical detection limit, a value of one-half of the detection limit is used for these samples. In this case this method is inadequate and will produce misleading statistical analysis because using one-half of the detection limit tends to underestimate the variability of the data and overestimate the mean of the data. In performing statistical tests this would lead us to decide that some trends were statistically significant when that was not the case. To deal with this problem a technique was developed for each metabolite using the trend of the data above the detection level to predict the trend for samples below the detection level. This method has been used to relate the concentration of urinary metabolites in children to values from the same household for adult urinary metabolites and pesticide concentrations in house dust.
Specific Aim 3. The underlying hypothesis for the Molecular Mechanisms Project of this Center is that pesticides alter neurobehavioral development by altering the dynamic relationship of cell proliferation and differentiation during early brain development. Of relevance for the Risk Characterization Core activities is the need for BBDR that will allow the effective description of dynamic processes such as early brain development. As mentioned in our original application, CHC investigators have established the basic framework for BBDR models for methylmercury neurodevelopmental effects during early organogenesis. In our last non-competitive renewal, we described how this basic dynamic model was being adapted in the programming language S Plus and was interfaced with kinetic models which use Simusolv to describe temporally relevant toxicokinetic parameters. Publications describing these linked dynamic interactive models are in final draft and will be submitted for publication early in year 3. A key focus of BBDR model development over this past year has been the expansion of the dynamic model to cover a larger range of brain development. The Molecular Mechanism Project is assessing neurodevelopmental impacts to the embryonic midbrain and the newborn hippocampal and cerebellar brain regions. To accommodate processes during this larger developmental time period we have utilized models evaluating neurodevelopmental impacts of ethanol. Modifications of the Leroux, et al. (1999) model are in process and will build on these detailed research investigations.
Significance. Collaboration with investigators on statistical designs and analysis has resulted in improved power of the studies to detect statistically significant results. The BBDR models under development improve our ability to evaluate the potential for neurodevelopmental impacts by better understanding how to interpret cell cycle data in terms of basic biological mechanisms of the developing and differentiating neurons. This two-stage stochastic neurodevelopmental BBDR model also assists in understanding basic biological mechanisms on a more complex level by linking exposures to toxic substances to actual tissue concentrations of the substances and their toxic effects on neurodevelopment. The work on temporal fallacies in evaluating biomarkers of exposures assists in development of better risks assessment methods for children’s environmental exposures and in the identification of susceptible time points for chemical impacts during neurodevelopment.
Risk Communication Core
Specific Aim 1. Tiffany Potter-Chiles, the Program Coordinator, continues to work closely with the field staff of the CIP in the Yakima Valley. She provides a critical link between investigators at the University of Washington and those at Fred Hutchinson Cancer Research Center, which administers the CIP. In cooperation with the Community Intervention staff, she created a coloring book to educate children about pesticides. Ms. Potter-Chiles also assisted in researching community services available in the Yakima Valley and created two brochures in English and Spanish, “Resources in our Community: Information about Pesticides” and “Resources in Our Community: Health and Community Services.”
During the second year, the CHC sponsored the following Department of Environmental Health seminars:
- Theodore Slotkin, Ph.D. (Duke University Medical Center), “Nicotine and chlorpyrifos: cholinergic agents targeting the developing brain,” February 10, 2000.
- Patricia M. Rodier, Ph.D. (University of Rochester), “Autism: a disorder with genetic & teratologic etiologies,” April 6, 2000.
- Stanley Barone, Jr., Ph.D. (U.S. Environmental Protection Agency), “Preliminary efforts at incorporating developmental effects of exposure to chlorpyrifos into a biologically-based dose response model,” April 27, 2000.
- Rob McConnell, M.D. (University of Southern California School of Medicine), “Asthma, lung function growth, and air pollution: results from the Southern California Children’s Health Study,” May 25, 2000.
Ms. Potter-Chiles also serves as a point of contact between community agencies, community members and UW investigators, providing information when appropriate and referring people to the appropriate investigator or community agency.
Specific Aim 2. Ms. Potter-Chiles researched and collected existing materials related to pesticides and risks to human health. The collection now includes books, journal articles, brochures, videos, pamphlets and posters that were created by government agencies, universities, and community organizations. These materials are cataloged and available to CHC researchers for reference.
Specific Aim 3. The UW CHC co-sponsored a continuing education course for medical professionals titled “Environmental health issues in children: what pediatricians and other primary care providers need to know.” The course was conducted by the UW Department of Environmental Health’s Continuing Education Program on April 28, 2000.
Specific Aim 4. Members of the UW CHC presented research findings at numerous workshops, conferences, and meetings throughout the year. A list of CHC presentations is included in the 2000 Annual Reports for R826886 and R826886C001-R826886C004.
The UW CHC attracted favorable media attention this year. The UW CHC was featured on the front page of the Seattle Times under the title “Are children at risk from pesticides: UW study aims to gauge the danger” (King, Warren, Seattle Times, August 22, 1999). The Associated Press carried a lengthy news release from Fred Hutchinson Cancer Research Center (FHCRC) on the results of the Community Intervention survey of farm workers; the AP article was carried in most regional newspapers including the Seattle Times, Post-Intelligencer, and the Yakima Herald. In addition to these feature stories, key investigators discussed CHC research and results with journalists on numerous occasions throughout the year.
Significance. Through the activities described above, the Risk Communication Core facilitates communication between UW investigators and the broader community. These activities contribute to the goal of the Risk Communication core to provide a link between Center investigators and the regional and national community on issues of environmental impacts to children’s health.
Administrative Core
During the second year the Administrative Core continued to provide administrative support for CHC research studies such as: fiscal management and budget reporting, purchasing, and subcontract management; development of communication materials; meeting coordination; and basic secretarial support. The Administrative staff coordinated six Center-wide meetings throughout the academic year. These meetings provided an effective venue for Center members to meet as a group to present research activities and results and to facilitate collaborative work. In addition to these internal meetings, the Administrative staff conducted the annual External Advisory Committee meeting in May 2000.
Ms. Potter-Chiles provided graphic design and publication support to the Community Intervention staff at FHCRC. She created several informative pieces including a coloring book and two brochures.
Ms. Woods and Ms. Prisbrey are contributing to the planning efforts of the upcoming National Institute of Environmental Health Sciences (NIEHS) Town Meeting, which will be hosted by the Department of Environmental Health’s Center for Ecogenetics and Environmental Health. The title of the meeting is “Voices for Healthy Environments, Healthy Communities.” The purpose of the Town Meeting is to bring together members of the community, scientists, policy makers, and regulators in a 2-day forum for discussion regarding environmental health issues in Washington State. Health risks related to pesticide exposure has been identified as a topic of discussion by the community planning committee, and a panel discussion will be conducted on this topic. In addition, the CHC administrative staff will coordinate with the Risk Communication group to create a visual display (poster) to present at the meeting. The town meeting will be held on September 29-30, 2000. Ms. Woods and Ms. Prisbrey are members of the community planning committee and the outreach committee and have been active since January 2000.
External Advisory Committee (EAC) Meeting. The EAC met for the second annual meeting on May 24, 2000. The EAC consists of six members: David L. Eaton, Ph.D. (Assistant Dean for Research, School of Public Health and Community Medicine; Professor and Director, Center for Ecogenetics and Environmental Health, Department of Environmental Health); Brenda Eskenazi, Ph.D. (Professor, University of California Berkeley; and Director of one of the Child Health Centers, “Exposures and Health of Farm Worker Children in California”); Lupe Gamboa, J.D. (Director, United Farmworkers of America); Carole A. Kimmel, Ph.D. (National Center for Environmental Assessment, U.S. Environmental Protection Agency); Rob McConnell, M.D. (Director, Pan American Health Association, Environmental Health Unit); and Lucina Suarez, Ph.D. (Senior Scientist, Texas Department of Health).
Internal Advisory Committee (IAC). The IAC comprises the Center Principal Investigator, the two Deputy Directors, the Program Administrator, and the Research Study and Core Directors. In the second year, the IAC meetings were combined with Center-wide meetings. At each of those meetings time was set aside to discuss administrative business prior to the general presentations on research activities. This format provided an excellent opportunity to discuss research collaborations and scientific review of activities.
Changes in CHC Projects and Personnel Implemented in Year 2 or Planned for Year 3. In February 2000, Susan Silbernagel accepted a position as Administrator in the UW Department of Pharmacology. Ruth Woods replaced Ms. Silbernagel as Program Administrator. Ms. Woods is the former fiscal manager of the Institute for Risk Analysis and Risk Communication (IRARC), which includes the CHC. She has been involved in the fiscal and contract management of the CHC since it was first proposed in 1997. This spring, Donna Prisbrey joined the CHC as a Program Assistant. Ms. Prisbrey brings to the Center experience working with diverse stakeholder groups and workshop planning. In the coming year, Ms. Potter-Chiles will further reduce her effort on the Center and she will focus her efforts on the design and publication of educational, outreach, and communication materials and the development of the Center Web Site. All Administrative personnel divide their effort between the Center and other IRARC programs.
Significance. N/A—administrative support core.
Future Activities:Neurobehavioral Assessment Core
During the remainder of this year and year 3, we will concentrate our efforts on the behavioral studies for the Pon1-knockout mice. Studies will be conducted examining both prenatal and postnatal exposure effects. We will begin with using a postnatal exposure model, since our previous studies have used this model. Preliminary studies will need to be performed to examine the appropriate dose range for the prenatal behavioral studies. It is anticipated that these studies will be conducted during year 3.
Exposure Assessment Core
Baseline sampling and laboratory analysis in support of the CIP is now complete. Significant effort in year 3 will be devoted to interpreting the CIP results. Exposure Core activities will also shift substantially to modeling support of the Pathways Project and other Center projects.
Risk Characterization Core
During the third year a replacement for Dr. Mary Lou Thompson will be hired. It is anticipated that collaboration and consultation with investigators on statistical design and analysis will continue to be an important part of our efforts. Publications are being developed on the models of temporal fallacy, flow cytometry model, and the two-stage stochastic neurodevelopmental toxicity model. It is anticipated that work on development of statistical methods for analyzing gene expression data from microarrays generated in the Molecular Mechanisms project will be carried out in year 3.
Risk Communication Core
Tiffany Potter-Chiles will continue to develop risk communication materials and publications for the UW CHC, including revising the CHC Web Site. She will work with Emily Allen (a member of the UW Pesticide Exposure Study and Community Intervention Study) to develop content for the Web site in a format and language that is readily accessible to non-scientists. This activity will support specific aim 4.
Administrative Core
No changes to plans are anticipated for year 3.
Journal Articles: 47 Displayed | Download in RIS Format
| Other center views: | All 83 publications | 51 publications in selected types | All 47 journal articles |
| Type | Citation | ||
|---|---|---|---|
|
|
Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE. Effects of 5’ regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. American Journal of Human Genetics 2001;68(6):1428-1436. |
R826886C002 (2001) R831709 (2005) |
|
|
|
Brophy V H, Hastings MD, Clendenning JB, Richter RJ, Jarvik GP, Furlong CE. Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 2001;11(1):77-84. |
R826886C002 (2001) R831709 (2005) |
|
|
|
Caughlan A, Newhouse K, Namgung U, Xia Z. Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases. Toxicological Sciences 2004;78(1):125-134. |
R831709C001 (2004) |
not available |
|
|
Costa LG, Li WF, Richter RJ, Shih DM, Lusis A, Furlong CE. The role of paraoxonase (PON1) in the detoxication of organophosphates and its human polymorphism. Chemico-Biological Interactions 1999;119-120:429-438. |
R826886C002 (2000) R831709 (2005) |
|
|
|
Costa LG. The emerging field of ecogenetics. NeuroToxicology 2000;21(1-2):85-89. |
R826886C002 (2000) R831709 (2005) |
|
|
|
Costa LG, Cole TB, Jarvik GP, Furlong CE. Functional genomics of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annual Review of Medicine 2003;54:371-392. |
R826886C002 (2002) |
|
|
|
Costa LG, Richter RJ, Li W-F, Cole T, Guizzetti M, Furlong CE. Paraoxonase (PON1) as a biomarker of susceptibility for organophosphate toxicity. Biomarkers 2003;8(1):1-12. |
R826886C002 (2002) R831709 (2005) R831709C002 (2004) |
|
|
|
Costa LG. Current issues in organophosphate toxicology. Clinica Chimica Acta 2006;366(1-2):1-13. |
R831709 (2005) R831709 (2006) R831709C001 (2006) |
|
|
|
Costa LG, Cole TB, Furlong CE. Gene-environment interactions: paraoxonase (PON1) and sensitivity to organophosphate toxicity. Lab Medicine 2006;37(2):109-113. |
R831709 (2005) R831709C001 (2007) R831709C002 (2007) |
not available |
|
|
Costa LG, Giordano G, Guizzetti M, Vitalone A. Neurotoxicity of pesticides: a brief review. Frontiers in Bioscience 2008;13(4):1240-1249. |
R831709 (2005) R831709 (2007) R831709C001 (2007) R831709C002 (2007) |
|
|
|
Curl CL, Fenske RA, Kissel JC, Shirai JH, Moate TW, Griffith W, Coronado G, Thompson B. Evaluation of take-home organophosphorus pesticide exposure among agricultural workers and their children. Environmental Health Perspectives 2002;110(12):A787-A792. |
R826886C003 (2001) R826886C003 (2002) R826886C004 (2001) R826886C004 (2002) R831709 (2005) |
|
|
|
Daston G, Faustman E, Ginsberg G, Fenner-Crisp P, Olin S, Sonawane B, Bruckner J, Breslin W. A framework for assessing risks to children from exposure to environmental agents. Environmental Health Perspectives 2004;112(2):238-256. |
R831709C001 (2004) |
not available |
|
|
Elgethun K, Fenske RA, Yost MG, Palcisko GJ. Time-location analysis for exposure assessment studies of children using a novel global positioning system instrument. Environmental Health Perspectives 2003;111(1):115-122. |
R826886C004 (2002) R831709 (2005) |
|
|
|
Elgethun K, Yost MG, Fitzpatrick CTE, NyergesTL, Fenske RA. Comparison of global positioning system (GPS) tracking and parent-report diaries to characterize children's time–location patterns. Journal of Exposure Science and Environmental Epidemiology 2007;17(2):196-206. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C004 (2006) R831709C004 (2007) |
|
|
|
Eskenazi B, Gladstone EA, Berkowitz GS, Drew CH, Faustman EM, Holland NT, Lanphear B, Meisel SJ, Perera FP, Rauh VA, Sweeney A, Whyatt RM, Yolton K. Methodologic and logistic issues in conducting longitudinal birth cohort studies: lessons learned from the Centers for Children’s Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1419-1429. |
R831709 (2005) R831709C001 (2004) R827027 (2002) R829389 (2003) R829389 (2004) R829389 (2005) R829390 (2005) R831710 (2005) R831711 (2005) R831711 (2006) R831711C001 (2006) R831711C002 (2004) R831711C002 (2006) R831711C003 (2006) R832141 (2005) |
|
|
|
Faustman EM, Silbernagel SM, Fenske RA, Burbacher TM, Ponce RA. Mechanisms underlying children’s susceptibility to environmental toxicants. Environmental Health Perspectives 2000;108(Suppl 1):13-21. |
R826886 (2000) R825173 (1999) R825173 (2000) R831709 (2005) |
|
|
|
Faustman EM, Gohlke, JM, Judd NL, Lewandowski TA, Bartell SA, Griffith WC. Modeling developmental processes in animals: Applications in neurodevelopmental toxicology. Environmental Toxicology and Pharmacology 2005;19(3):615-624. |
R831709 (2005) R831709 (2006) R831709C001 (2004) R831709C001 (2005) R831709C001 (2006) |
|
|
|
Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen EH, Keifer MC. Biologically based pesticide dose estimates for children in an agricultural community. Environmental Health Perspectives 2000;108(6):515-520. |
R826886C004 (2001) R831709 (2005) |
|
|
|
Fenske RA, Lu C, Simcox NJ, Loewenherz C, Touchstone J, Moate TF, Allen EH, Kissel JC. Strategies for assessing children’s organophosphorus pesticide exposures in agricultural communities. Journal of Exposure Analysis and Environmental Epidemiology 2000;10(6 Suppl 2):662-671. |
R826886C004 (2001) R825171 (2000) R831709 (2005) |
|
|
|
Furlong CE, Li WF, Richter RJ, Shih DM, Lusis AJ, Alleva E, Costa LG. Genetic and temporal determinants of pesticide sensitivity: role of paraoxonase (PON1). NeuroToxicology 2000;21(1-2):91-100. |
R826886C002 (2000) R826886C002 (2001) R831709 (2005) |
|
|
|
Furlong CE, Li WF, Brophy VH, Jarvik GP, Richter RJ, Shih DM, Lusis AJ, Costa LG. The PON1 gene and detoxication. NeuroToxicology 2000;21(4):581-587. |
R826886C002 (2001) R831709 (2005) |
|
|
|
Furlong CE, Li W-F, Shih DM, Lusis AJ, Richter RJ, Costa LG. Genetic factors in susceptibility:serum PON1 variation between individuals and species. Human and Ecological Risk Assessment 2002;8(1):31-43. |
R826886C002 (2002) R831709 (2005) |
|
|
|
Furlong CE, Cole TB, Jarvik GP, Costa LG. Pharmacogenomic considerations of the paraoxonase polymorphisms. Pharmacogenomics 2002;3(3):341-348. |
R826886C002 (2002) R831709 (2005) |
|
|
|
Giordano G, Afsharinejad Z, Guizzetti M, Vitalone A, Kavanagh TJ, Costa LG. Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency. Toxicology and Applied Pharmacology 2007;219(2-3):181-189. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C001 (2006) R831709C001 (2007) R831709C002 (2007) |
|
|
|
Gohlke JM, Griffith WC, Faustman EM. The role of cell death during neocortical neurogenesis and synaptogenesis: implications from a computational model for the rat and mouse. Developmental Brain Research 2004;151(1-2):43-54. |
R831709 (2005) R831709C001 (2004) |
not available |
|
|
Gohlke JM, Griffith WC, Faustman EM. A systems-based computational model for dose-response comparisons of two mode of action hypotheses for ethanol-induced neurodevelopmental toxicity. Toxicology Science 2005;86:470-84. |
R831709 (2004) R831709 (2005) R831709C001 (2005) |
not available |
|
|
Guizzetti M, Pathak S, Giordano G, Costa LG. Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation. Toxicology 2005;215(3):182-190. |
R831709 (2005) R831709 (2006) R831709C001 (2005) R831709C001 (2006) R831709C002 (2006) |
|
|
|
Lewandowski TA, Ponce RA, Charleston JS, Hong S, Faustman EM. Changes in cell cycle parameters and cell number in the rat midbrain during organogenesis. Developmental Brain Research 2003;141(1-2):117-128. |
R831709 (2005) R831709C001 (2004) |
not available |
|
|
Lewandowski TA, Ponce RA, Charleston JS, Hong S, Faustman EM. Effect of methylmercury on midbrain cell proliferation during organogenesis: potential cross-species differences and implications for risk assessment. Toxicological Sciences 2003;75(1):124-133. |
R831709 (2005) R831709C001 (2004) |
not available |
|
|
Li WF, Costa LG, Richter RJ, Hagen T, Shih DM, Tward A, Lusis AJ, Furlong CE. Catalytic efficiency determines the in- vivo efficacy of PON1 for detoxifying organophosphorus compounds. Pharmacogenetics 2000;10(9):767-779. |
R826886C002 (2000) R826886C002 (2001) R831709 (2005) |
|
|
|
Lu C, Fenske RA. Dermal transfer of chlorpyrifos residues from residential surfaces: comparison of hand press, hand drag, wipe, and polyurethane foam roller measurements after broadcast and aerosol pesticide applications. Environmental Health Perspectives 1999;107(6):463-467. |
R826886C004 (2001) R831709 (2005) |
|
|
|
Lu C, Fenske RA, Simcox NJ, Kalman D. Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environmental Research 2000;84(3):290-302. |
R826886C004 (2001) R831709 (2005) |
|
|
|
Mirkes PE, Little SA. Cytochrome c release from mitochondria of early postimplantation murine embryos exposed to 4-hydroperoxycyclophosphamide, heat shock, and staurosporine. Toxicology and Applied Pharmacology 2000;162(3):197-206. |
R826886C001 (2001) R831709 (2005) |
|
|
|
Mirkes PE, Wilson KL, Cornel LM. Teratogen-induced activation of ERK, JNK, and p38 MAP kinases in early postimplantation murine embryos. Teratology 2000;62(1):14-25. |
R826886C001 (2001) R831709 (2005) |
|
|
|
Moate TF, Lu C, Fenske RA, Hahne RMA, Kalman DA. Improved cleanup and determination of dialkyl phosphates in the urine of children exposed to organophosphorus insecticides. Journal of Analytical Toxicology 1999;23(4):230-236. |
R826886C004 (2001) R825171 (1999) R825171 (2000) R831709 (2005) |
|
|
|
Moate TF, Furia M, Curl C, Muniz JF, Yu J, Fenske RA. Size exclusion chromatographic cleanup for GC/MS determination of organophosphorus pesticide residues in household and vehicle dust. Journal of AOAC International 2002;85(1):36-43. |
R826886C004 (2001) R826886C004 (2002) R831709 (2005) |
|
|
|
Namgung U, Xia Z. Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and p38 MAP kinases. Toxicology and Applied Pharmacology 2001;174(2):130-138. |
R826886C001 (2002) R831709 (2005) |
|
|
|
Ramaprasad J, Tsai M-Y, Elgethun K, Hebert VR, Felsot A, Yost MG, Fenske RA. The Washington aerial spray drift study: assessment of off-target organophosphorus insecticide atmospheric movement by plant surface volatilization. Atmospheric Environment 2004;38(33):5703-5713. |
R831709 (2005) R831709C004 (2004) |
not available |
|
|
Sidhu JS, Ponce RA, Vredevoogd MA, Yu X, Gribble E, Hong S-W, Schneider E, Faustman EM. Cell cycle inhibition by sodium arsenite in primary embryonic rat midbrain neuroepithelial cells. Toxicological Sciences 2006;89(2):475-484. |
R831709 (2005) R831709 (2006) R831709C001 (2005) R831709C001 (2006) |
|
|
|
Thompson B, Coronado G, Puschel K, Allen E. Identifying constituents to participate in a project to control pesticide exposure in children of farmworkers. Environmental Health Perspectives 2001;109(Suppl 3):443-448. |
R826886C003 (2001) R826886C003 (2002) R826886C004 (2001) R826886C004 (2002) R831709 (2005) |
|
|
|
Thompson B, Coronado GD, Grossman JE, Puschel K, Solomon CC, Islas I, Curl CL, Shirai JH, Kissel JC, Fenske RA. Pesticide take-home pathway among children of agricultural workers: study design, methods, and baseline findings. Journal of Occupational and Environmental Medicine 2003;45(1):42-53. |
R826886C003 (2002) R831709 (2005) R831709C003 (2004) |
|
|
|
Tsai M-Y, Elgethun K, Ramaprasad J, Yost MG, Felsot AS, Hebert VR, Fenske RA. The Washington aerial spray drift study:modeling pesticide spray drift deposition from an aerial application. Atmospheric Environment 2005;39(33):6194-6203. |
R831709 (2005) R831709C004 (2005) R831709C004 (2006) |
|
|
|
Umpierre CC, Little SA, Mirkes PE. Co-localization of active caspase-3 and DNA fragmentation (TUNEL) in normal and hyperthermia-induced abnormal mouse development. Teratology 2001;63(3):134-143. |
R826886C001 (2001) R826886C001 (2002) R831709 (2005) |
|
|
|
Vicini P, Pierce CH, Dills RL, Morgan MS, Kalman DA. Individual prior information in a physiological model of 2H8-toluene kinetics: an empirical Bayes estimation strategy. Risk Analysis 1999;19(6):1127-1134. |
R826886 (2000) |
|
|
|
Weppner S, Elgethun K, Lu C, Herbert V, Yost MG, Fenske RA. The Washington aerial spray drift study: children's exposure to methamidophos in an agricultural community following fixed-wing aircraft applications. Journal of Exposure Science and Environmental Epidemiology 2006;16(5):387-396. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C004 (2006) R831709C004 (2007) |
|
|
|
Yu X, Griffith WC, Hanspers K, Dillman III JF, Ong H, Vredevoogd MA, Faustman EM. A system-based approach to interpret dose-and time-dependent microarray data: quantitative integration of gene ontology analysis for risk assessment. Toxicological Sciences 2006;92(2):560-577. |
R831709 (2005) R831709 (2006) R831709C001 (2006) R832733 (2007) |
|
|
|
Gribble EJ, Hong S-W, Faustman EM. The magnitude of methylmercury-induced cytotoxicity and cell cycle arrest is p53 dependent. Birth Defects Research Part A: Clinical and Molecular Teratology 2005;73(1):29-38. |
R831709 (2005) R831709C001 (2004) |
not available |
Geographic Area, Scientific Discipline, Health, RFA, Risk Assessments, Health Risk Assessment, Epidemiology, Children's Health, Biochemistry, Environmental Chemistry, State, exposure assessment, insecticides, developmental neurotoxicology, developmental disorders, health effects, Washington (WA), developmental effects, epidemelogy, developmental toxicity, children's environmental health, organophosphate pesticides, assessment of exposure, harmful environmental agents, human health risk, epidemeology, developmental neurotoxicity, agricultural community, pesticide exposure, environmental health, children, pesticides, exposure, growth & development, children's vulnerablity, environmental health hazard, human exposure, Human Health Risk Assessment, neurotoxicity
Relevant Websites:
http://depts.washington.edu/chc/
Progress and Final Reports:
Original Abstract
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826886C001 Molecular Mechanisms of Pesticide-Induced Developmental Toxicity
R826886C002 Genetic Susceptibility to Pesticides (Paraoxonase Polymorphism or PON1 Study)
R826886C003 Community-Based Participatory Research Project
R826886C004 Pesticide Exposure Pathways Research Project