Grantee Research Project Results
2006 Progress Report: Center for Child Environmental Health Risks Research
EPA Grant Number: R831709Center: Center for Air, Climate, and Energy Solutions
Center Director: Robinson, Allen
Title: Center for Child Environmental Health Risks Research
Investigators: Faustman, Elaine
Institution: University of Washington
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Period Covered by this Report: November 1, 2005 through October 31,2006
Project Amount: $3,651,710
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health
Objective:
The University of Washington Center for Child Environmental Health Risks Research (CHC) was established in 1998. The theme of the Center is understanding the biochemical, molecular, and exposure mechanisms that define children's susceptibility to pesticides and the implications for assessing pesticide risks to normal development and learning. The CHC is a multidisciplinary research program that conducts basic and applied mechanistic research aimed at reducing the adverse effects of environmental pesticide exposures in children. The Center’s research program includes basic mechanistic studies of toxicity, exposure assessment, risk assessment, and community-based participatory research. Researchers from the University of Washington (UW) and the Fred Hutchinson Cancer Research Center work in the laboratory, field, and community to bring a unique and successful approach to the study of children’s environmental health. It is administratively housed within the Institute for Risk Analysis and Risk Communication in the UW School of Public Health and Community Medicine.
To facilitate both basic and applied research on reducing the adverse effects of environmental pesticide exposures, Center participants include members from multiple institutions, schools, and varied departments and clinics. To achieve tangible effects on the community, the CHC includes a partnership with an eastern Washington community within the Yakima Valley agricultural center of our state to jointly accomplish pesticide intervention with reduced childhood pesticide exposures.
The specific objectives of the Center are to: (1) identify cellular, biochemical, and molecular mechanisms for the adverse developmental neurotoxicity of pesticides; (2) identify susceptibility factors for developmental neurotoxicity of pesticides, including genetic polymorphisms; (3) improve our understanding of critical pathways of pesticide exposure for children; (4) intervene to reduce children’s exposure to pesticides, including the development of a culturally appropriate intervention to break the take-home pathway; (5) provide core support for the development and application of risk assessment methods, which will enable basic research on pesticide toxicity and exposure to be translated for improved child health by informing risk decisions to protect children’s health from pesticides; and (6) foster partnerships between academic researchers and the community in which information requested by the community and basic research deficiencies/gaps are translated into studies that address the health needs of both.
The CHC is comprised of two laboratory-based research projects, two field-based projects, and four facility cores. The four facility cores (Neurobehavioral Assessment, Exposure Assessment, Risk Characterization, and Risk Communication) are designed to support the research agenda and to put the research into a child specific risk assessment context. Thus, the scientific findings on pesticide toxicity and exposure can be incorporated directly into risk assessment models that are designed to protect child health.
Approach:
The CHC is comprised of two laboratory based research projects, two field based projects, and four facility cores. The four facility cores (Neurobehavioral Assessment, Exposure Assessment, Risk Characterization and Risk Communication) are designed to support the research agenda and to put the research into a child specific risk assessment context. Thus the scientific findings on pesticide toxicity and exposure can be directly incorporated into risk assessment models that are designed to protect child health.
Highlights of Research Projects:
Molecular Mechanisms of Pesticide Induced Developmental Neurotoxicity
The Molecular Mechanisms Research Project specifically evaluates the molecular and cellular mechanisms of toxicity through which pesticides can exert their neurodevelopmental toxicity. Alterations in the regulatory dynamics of neural cell proliferation, differentiation, and cell death are examined.
We are investigating two of the most commonly used organophosphate pesticides - chlorpyrifos and diazinon, as well as persistent pesticides that were used historically. We focus on the molecular and cellular mechanisms of toxicity during “windows of susceptibility,” the periods during which these pesticides can cause neurodevelopmental toxicity and disease. A systems biology based assessment integrates in vitro and in vivo studies (as well as toxicogenomic assessments) across endpoints and functional outcomes using Physiologically Based Toxicokinetic (PBTK) and Biologically Based Dose Response (BBDR) models. This approach allows for evaluation of the mechanisms of action including gene environment interactions on cell cycle regulation, oxidative stress and apoptosis. Neurodevelopmental models for normal as well as toxicant perturbed neocortical development (including neurogenesis and synaptogenesis) have been created. The systems biology approach that our center employs, and links with neurobehavioral function, leads to an integrated understanding of the critical pesticide exposures associated with neurodevelopmental toxicity.
Genetic Susceptibility to Pesticides
The Genetic Susceptibility Research Project examines gene/environment interactions important for children’s health by evaluating differences in genetics that affect metabolism and define susceptibility. The overall aim of this research project is to investigate the developmental neurotoxicity of the organophosphates chlorpyrifos oxon and diazoxon, and to determine the role of genetic variability in the polymorphic serum enzyme paraoxonase (PON1) in protecting against developmental neurotoxicity.
Recent studies in humans (run in collaboration with the UC-Berkeley CHAMACOS) have shown that developmental onset of PON1 is highly variable among children. It can appear at ages as early as four months and as late as two years. Inter-individual variability in PON1192 genotype, PON-1 levels and development time course means that children can have different susceptibilities to adverse effects of pesticides. The contribution of PON1 to pesticide toxicity has had profound effects for understanding human health and now its role in defining children’s susceptibility is under investigation.
Community-Based Participatory Research Project
The overall goal of the Community Based Participatory Research Project (CBPR) is to investigate multiple pathways that may contribute to pesticide exposure in adults and children living in agricultural communities.
The community-based research project has evaluated the impacts of the occupational take home pathway on pesticide exposure in children of farmworkers. Concentrations of OP pesticide metabolites in the urine of farmworkers and their children were correlated with concentrations of OP pesticide residues in vehicle and house dust. Concentrations were higher in households with an adult who worked in apple and/or pear orchards. Consistent with our findings, these fruit crops had the highest amounts of OP pesticides applied per acre. In addition, the Center is collecting longitudinal data to gain an understanding of the effects of within person variability versus between person variability to better identify an exposed cohort within a population by using a limited number of bioassays.
Pesticide Spray Drift Study
The overall objective of this project is to understand the underlying physical and behavioral mechanisms by which non-occupational exposure occurs following pesticide applications.
One study measured airborne concentrations of pesticides in a community during and after a spray event. The study investigated assumptions that are made to ensure the safe application of pesticides. Results revealed that the existing volatilization model under-predicted (by about 4 fold) the measured pesticide concentration after the spray event when temperatures rose significantly. This indicates a need to re-examine inhalation exposures for pesticides when the temperature is high. Further, when linked with our study examining children’s activity profiles, the spray drift study suggests a need to re-evaluate transport modeling and exposure factors.
Important research findings from the UW Center:
Contributions of occupational factors to home contamination -- Evidence of Take-home Pathway
- Higher concentrations of OP pesticide dimethyl metabolites in the urine of farmworkers and their children were correlated with higher concentrations of azinphos-methyl pesticide residue in vehicle and house dust.
- Children of orchard workers have an additional source of pesticide exposure through pesticides that are transported on the clothing, boots and skin of their farmworker parents.
Contributions of occupational factors to home contamination -- Evidence of Crop-associated Exposure
- Concentrations of OP pesticide dimethyl metabolites in the urine of farmworkers and their children and concentrations of azinphos-methyl pesticide residue in vehicle and house dust were higher among farmworker households employed in the pome fruit crops.
- Consistent with these findings, the pome fruit crops of apples and pears had the highest amounts of OP pesticides applied per acre, in particular azinphos-methyl.
- After controlling for crop, we did not detect differences in exposure between farmworkers performing varying job tasks.
Exposure Assessment Study
- Analyzed three longitudinal studies of OP metabolites (WA, MN, and MD) and estimated within and between person variability.
- Within child variation larger than between child variations.
- Large within child variability for OP pesticide biomarkers limits ability to identify exposed populations.
PON1 Status of farmworker mothers and children
(Study conducted in collaboration with UC-Berkeley CHAMACOS)
- 8 – 10-fold variability in sensitivity to CPO between groups of mothers and their newborns.
Production of ‘Humanized’ Transgenic Mouse Lines Carrying hPON1Q192 or hPON1R192 in Place of Mouse PON1
- PON1Q192 mice were twice as sensitive as PON1R192 mice to brain ChE inhibition by chlorpyrifos oxon (CPO).
- PON1Q192 mice were more sensitive than PON1R192 mice to neocortical histopathology resulting from chronic developmental exposure to low doses (0.18-0.25 mg/kg/d) of CPO.
Washington Pesticide Spray Drift Study
- A new method of using small backpacks equipped with GPS for tracking children’s movements was developed to better understand children’s movements throughout the day.
- An innovative laser-based system (LIDAR) of real-time measurement of drift during pesticide-spraying was developed. Observations made with this system have resulted in a reassessment of methods to estimate exposures from pesticide drift currently used at the EPA.
Progress Summary:
To complete the Center objectives, the following projects have been initiated:
Project 1 (R831709C001): Molecular Mechanisms of Pesticide-Induced Developmental Toxicity.
Project 2 (R831709C002): Genetic Susceptibility to Pesticides.
Project 3 (R831709C003): Community-Based Participatory Research Project.
Project 4 (R831709C004): Pesticide Exposure Pathways Research Project.
Please see the individual 2006 Annual Reports for R831709C001, R831709C002, R831709C003, and R831709C004 for specific progress summaries and accomplishments.
Future Activities:
Please see the future activities included in the individual 2006 Annual Reports for R831709C001, R831709C002, R831709C003, and R831709C004.
Journal Articles: 107 Displayed | Download in RIS Format
| Other center views: | All 175 publications | 127 publications in selected types | All 107 journal articles |
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Bal-Price AK, Sunol C, Weiss DG, van Vliet E, Westerink RHS, Costa LG . Application of in vitro neurotoxicity testing for regulatory purposes:Symposium III summary and research needs. Neurotoxicology 2008;29(3):520-531. |
R831709 (2007) |
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Bartell SM, Ponce RA, Sanga RN, Faustman EM. Human variability in mercury toxicokinetics and steady state biomarker ratios. Environmental Research 2000;84(2):127-132. |
R831709 (2007) |
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Bekris LM, Shephard C, Janer M, Graham J, McNeney B, Shin J, Zarghami M, Griffith W, Farin F, Kavanagh TJ, Lernmark A. Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels. Experimental and Clinical Endocrinology and Diabetes 2007;115(4):221-228. |
R831709 (2005) R831709 (2007) R832733 (2007) |
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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. |
R831709 (2007) R826886 (2000) R826886C002 (2001) |
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Burry M, Guizzetti M, Oberdoerster J, Costa LG. Developmental neurotoxicity of toluene:in vivo and in vitro effects on astroglial cells. Developmental Neuroscience 2003;25(1):14-19. |
R831709 (2005) R831709 (2007) |
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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. |
R831709 (2007) R831709C001 (2004) |
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Cole TB, Jampsa RL, Walter BJ, Arndt TL, Richter RJ, Shih DM, Tward A, Lusis AJ, Jack RM, Costa LG, Furlong CE. Expression of human paraoxonase (PON1) during development. Pharmacogenetics 2003;13(6):357-364. |
R831709 (2005) R831709 (2007) |
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Cole TB, Walter BJ, Shih DM, Tward AD, Lusis AJ, Timchalk C, Richter RJ, Costa LG, Furlong CE. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism. Pharmacogenetics and Genomics 2005;15(8):589-598. |
R831709 (2005) R831709C002 (2005) |
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Cole TB, Jansen K, Park S, Li W-F, Furlong CE, Costa LG. The toxicity of mixtures of specific organophosphate compounds is modulated by paraoxonase 1 status. Advances in Experimental Medicine and Biology 2010;660:47-60. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) R834514C004 (Final) |
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Coronado GD, Thompson B, Strong L, Griffith WC, Islas I. Agricultural task and exposure to organophosphate pesticides among farmworkers. Environmental Health Perspectives 2004;112(2):142-147. |
R831709 (2005) R831709 (2007) R831709C003 (2004) |
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Coronado GD, Thompson B, Griffith WC. Children's exposure to OP pesticides:response to Fenske et al. Environmental Health Perspectives 2004;112(15):A866 (correspondence). |
R831709 (2005) R831709C003 (2005) |
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Coronado GD, Thompson B, Griffith WC. Children's exposure to OP pesticides: response to Fenske et al. Environmental Health Perspectives 2004;112(15):A866-A866. |
R831709 (2007) |
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Coronado GD, Thompson B, Strong L, Griffith WC, Islas I. Activities and organophosphate exposures: response. Environmental Health Perspectives 2004;112(13):A725-A726 (correspondence). |
R831709 (2005) R831709 (2007) R831709C003 (2005) |
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Coronado GD, Vigoren EM, Thompson B, Griffith WC, Faustman EM. Organophosphate pesticide exposure and work in pome fruit:evidence for the take-home pesticide pathway. Environmental Health Perspectives 2006;114(7):999-1006. |
R831709 (2005) R831709 (2007) R831709C003 (2006) |
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Coronado GD, Vigoren EM, Griffith WC, Faustman EM, Thompson B. Organophosphate pesticide exposure among pome and non-pome farmworkers:a subgroup analysis of a community randomized trial. Journal of Occupational and Environmental Medicine 2009;51(4):500-509. |
R831709 (2007) R832734 (Final) R834514 (2011) R834514 (Final) R834514C001 (Final) |
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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. |
R831709 (2005) R831709 (2007) R831709C002 (2004) R826886 (2000) R826886C002 (2002) |
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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. |
R831709 (2005) R831709 (2007) R831709C002 (2004) R826886 (2000) R826886C002 (2002) |
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Costa LG, Cole TB, Furlong CE. Polymorphisms of paraoxonase (PON1) and their significance in clinical toxicology of organophosphates. Clinical Toxicology 2003;41(1):37-45. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
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Costa LG, Aschner M, Vitalone A, Syversen T, Soldin OP. Developmental neuropathology of environmental agents. Annual Review of Pharmacology and Toxicology 2004;44:87-110. |
R831709 (2005) R831709 (2007) |
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Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochemical Pharmacology 2005;69(4):541-550. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
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Costa LG, Cole TB, Vitalone A, Furlong CE. Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clinica Chimica Acta 2005;352(1-2):37-47. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
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Costa LG, Cole TB, Furlong CE. Paraoxonase (PON1): from toxicology to cardiovascular medicine. Acta Biomedica 2005;76(Suppl 2):50-57. |
R831709 (2005) |
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Costa LG. Current issues in organophosphate toxicology. Clinica Chimica Acta 2006;366(1-2):1-13. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C001 (2006) |
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Costa LG, Cole TB, Furlong CE. Gene-environment interactions:paraoxonase (PON1) and sensitivity to organophosphate toxicity. LabMedicine 2006;37(2):109-113. |
R831709 (2005) R831709 (2007) R831709C001 (2007) R831709C002 (2007) |
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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) |
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Cullen AC, Corrales MA, Kramer CB, Faustman EM. The application of genetic information for regulatory standard setting under the clean air act:a decision-analytic approach. Risk Analysis 2008;28(4):877-890. |
R831709 (2007) |
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Curl CL, Fenske RA, Elgethun K. Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Environmental Health Perspectives 2003;111(3):377-382. |
R831709 (2005) R831709 (2007) |
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Daston G, Faustman E, Ginsberg G, Fenner-Crisp P, Olin S, Sonawane B, Bruckner J, Breslin W, McLaughlin TJ. A framework for assessing risks to children from exposure to environmental agents. Environmental Health Perspectives 2004;112(2):238-256. |
R831709 (2007) R831709C001 (2004) |
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Drew CH, Grace DA, Silbernagel SM, Hemmings ES, Smith A, Griffith WC, Takaro TK, Faustman EM. Nuclear waste transportation:case studies of identifying stakeholder risk information needs. Environmental Health Perspectives 2003;111(3):263-272. |
R831709 (2005) R831709 (2007) |
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Eaton DL, Daroff RB, Autrup H, Bridges J, Buffler P, Costa LG, Coyle J, McKhann G, Mobley WC, Nadel L, Neubert D, Schulte-Hermann R, Spencer PS. Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. Critical Reviews in Toxicology 2008;38(Supplement 2):1-125. |
R831709 (2007) |
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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. |
R831709 (2005) R831709 (2007) R826886 (2000) R826886C004 (2002) |
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Elgethun K, Yost MG, Fitzpatrick CTE, Nyerges TL, 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) |
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Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland NT. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environmental Health Perspectives 2004;112(10):1116-1124. |
R831709 (2007) R831709C002 (2004) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2004) |
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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) R829389 (Final) R829390 (2005) R829390 (Final) R829390C002 (2005) R831710 (2005) R831710 (Final) R831710C001 (2006) R831710C002 (2006) R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2004) R831711C002 (2006) R831711C003 (2006) R832141 (2005) R832141 (2007) R832141 (Final) |
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Faustman EM, Gohlke J, Judd NL, Lewandowski TA, Bartell SM, Griffith WC. Modeling developmental processes in animals:applications in neurodevelopmental toxicology. Environmental Toxicology and Pharmacology 2005;19(3):615-624. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C001 (2004) R831709C001 (2005) R831709C001 (2006) |
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Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers:an analysis of recent studies in Washington State. Environmental Health Perspectives 2005;113(11):1651-1657. |
R831709 (2005) R831709 (2007) |
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Fenske RA, Bradman A, Whyatt RM, Wolff MS, Barr DB. Lessons learned for the assessment of children's pesticide exposure: critical sampling and analytical issues for future studies. Environmental Health Perspectives 2005;113(10):1455-1462. |
R831709 (2005) R831709 (2007) R827027 (2002) R831710 (2004) R831710 (2005) R831710 (Final) R831711 (2004) R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2006) R831711C003 (2006) R832141 (2006) R832141 (2007) R832141 (Final) |
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Furlong CE, Cole TB, Jarvik GP, Pettan-Brewer C, Geiss GK, Richter RJ, Shih DM, Tward AD, Lusis AJ, Costa LG. Role of paraoxonase (PON1) status in pesticide sensitivity:genetic and temporal determinants. Neurotoxicology 2005;26(4):651-659. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
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Furlong CE, Cole TB, Walter BJ, Shih DM, Tward A, Lusis AJ, Timchalk C, Richter RJ, Costa LG. Paraoxonase 1 (PON1) status and risk of insecticide exposure. Journal of Biochemical and Molecular Toxicology 2005;19(3):182-183. |
R831709 (2005) R831709 (2007) R831709C002 (2005) |
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Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B. PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenetics and Genomics 2006;16(3):183-190. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C002 (2006) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2007) R831710C003 (2006) R831710C003 (2007) |
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Furlong CE. Genetic variability in the cytochrome P450-paraoxonase 1 (PON1) pathway for detoxication of organophosphorus compounds. Journal of Biochemical and Molecular Toxicology 2007;21(4):197-205. |
R831709 (2005) R831709 (2007) |
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Furlong CE, Suzuki SM, Stevens RC, Marsillach J, Richter RJ, Jarvik GP, Checkoway H, Samii A, Costa LG, Griffith A, Roberts JW, Yearout D, Zabetian CP. Human PON1, a biomarker of risk of disease and exposure. Chemico-Biological Interactions 2010;187(1-3):355-361. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) |
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Garry MR, Kavanagh TJ, Faustman EM, Sidhu JS, Liao R, Ware C, Vliet P, Deeb S. Sensitivity of mouse lung fibroblasts heterozygous for GPx4 to oxidative stress. Free Radical Biology and Medicine 2008;44(6):1075-1087. |
R831709 (2005) R831709 (2007) |
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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) |
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Giordano G, Pizzurro D, VanDeMark KL, Guizzetti M, Costa LG. Manganese inhibits the ability of astrocytes to promote neuronal differentiation. Toxicology and Applied Pharmacology 2009; 240(2):226-235. |
R831709 (2007) |
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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) R831709 (2007) R831709C001 (2004) |
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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. Toxicological Sciences 2005;86(2):470-484. |
R831709 (2004) R831709 (2005) R831709 (2007) R831709C001 (2005) |
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Gohlke JM, Griffith WC, Faustman EM. Computational models of neocortical neuronogenesis and programmed cell death in the developing mouse, monkey, and human. Cerebral Cortex 2007;17(10):2433-2442. |
R831709 (2005) R831709 (2007) |
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Gohlke JM, Griffith WC, Faustman EM. Computational models of ethanol-induced neurodevelopmental toxicity across species:implications for risk assessment. Birth Defects Research Part B. Developmental and Reproductive Toxicology 2008;83(1):1-11. |
R831709 (2007) |
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Gribble EJ, Hong SW, 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) R831709 (2007) R831709C001 (2004) |
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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) R831709 (2007) R831709C001 (2005) R831709C001 (2006) R831709C002 (2006) |
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Guizzetti M, Moore NH, Giordano G, Costa LG. Modulation of neuritogenesis by astrocyte muscarinic receptors. Journal of Biological Chemistry 2008;283(46):31884-31897. |
R831709 (2007) |
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Guizzetti M, Moore NH, Giordano G, VanDeMark KL, Costa LG. Ethanol inhibits neuritogenesis induced by astrocyte muscarinic receptors. Glia 2010;58(12):1395-1406. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) |
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Hetman M, Hsuan SL, Habas A, Higgins MJ, Xia Z. ERK1/2 antagonizes glycogen synthase kinase-3beta-induced apoptosis in cortical neurons. Journal of Biological Chemistry 277(51):49577-49584. |
R831709 (2005) R831709 (2007) |
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Holland N, Furlong C, Bastaki M, Richter R, Bradman A, Huen K, Beckman K, Eskenazi B. Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns. Environmental Health Perspectives 2006;114(7):985-991. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C002 (2006) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2007) R831710C003 (2006) R832734 (2006) R832734 (2007) R832734 (Final) |
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Huen K, Richter R, Furlong C, Eskenazi B, Holland N. Validation of PON1 enzyme activity assays for longitudinal studies. Clinica Chimica Acta 2009;402(1-2):67-74. |
R831709 (2007) R831710 (Final) R832734 (2009) R832734 (Final) R834513 (2010) R834513 (2011) R834513 (Final) |
Exit |
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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. |
R831709 (2005) R831709 (2007) R831709C003 (2005) R831709C003 (2006) R826710 (Final) R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2006) R831710C002 (2006) R831710C004 (2006) R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2006) R831711C003 (2006) R832139 (2006) |
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Jarvik GP, Jampsa R, Richter RJ, Carlson CS, Rieder MJ, Nickerson DA, Furlong CE. Novel paraoxonase (PON1) nonsense and missense mutations predicted by functional genomic assay of PON1 status. Pharmacogenetics 2003;13(5):291-295. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
Exit |
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Judd NL, Griffith WC, Takaro T, Faustman EM. A model for optimization of biomarker testing frequency to minimize disease and cost:example of beryllium sensitization testing. Risk Analysis 2003; 23(6):1211-1220. |
R831709 (2005) R831709 (2007) |
Exit |
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Judd NL, Karr JR, Griffith WC, Faustman EM. Challenges in defining background levels for human and ecological risk assessments.Human and Ecological Risk Assessment:An International Journal 2003; 9(7):1623-1632. |
R831709 (2005) R831709 (2007) |
Exit |
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Judd NL, Griffith WC, Kalman DA, Faustman EM. Assessment of PCB congener analytical methods:do they meet risk assessment needs? Archives of Environmental Contamination and Toxicology 2003; 44(1):132-139. |
R831709 (2005) R831709 (2007) |
Exit Exit |
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Judd NL, Griffith WC, Faustman EM. Consideration of cultural and lifestyle factors in defining susceptible populations for environmental disease. Toxicology 2004;198(1-3):121-133. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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Judd N, Griffith WC, Faustman EM. Contribution of PCB exposure from fish consumption to total dioxin-like dietary exposure. Regulatory Toxicology and Pharmacology 2004;40(2):125-135. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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Kelada SN, Costa-Mallen P, Checkoway H, Viernes HA, Farin FM, Smith-Weller T, Franklin GM, Costa LG, Longstreth Jr WT, Furlong CE, Javrik GP, Swanson PD. Paraoxonase 1 promoter and coding region polymorphisms in Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry 2003;74(4):546-547. |
R831709 (2005) R831709 (2007) R831709C002 (2004) |
Exit Exit Exit |
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Kelada SN, Stapleton PL, Farin FM, Bammler TK, Eaton DL, Smith-Weller T, Franklin GM, Swanson PD, Longstreth Jr WT, Checkoway H. Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease. Neuroscience Letters 2003;337(1):5-8. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB, Needham LL, Fenske RA. Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(2):164-171. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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Koo B, Gaydos TM, Pandis SN. Evaluation of the equilibrium, dynamic, and hybrid aerosol modeling approaches. Aerosol Science and Technology 2003;37(1):53-64. |
R831709 (2007) R831709C003 (2004) R826371 (Final) R826371C005 (Final) |
Exit Exit |
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Latowsky G. Report: Community-based, participatory research in Lawrence, Massachusetts, flags environmental health hazards and fuels education and action. Science Communication 2003;25(2):204-208. |
R831709 (2006) R831709 (2007) R828596 (2004) |
Exit |
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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) R831709 (2007) R831709C001 (2004) |
Exit Exit Exit |
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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) R831709 (2007) R831709C001 (2004) |
Exit Exit Exit |
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Livaudais JC, Thompson B, Islas I, Ibarra G, Anderson J, Coronado GD. Workplace exposures and protective practices of Hispanic warehouse workers. Journal of Immigrant and Minority Health 2009;11(2):122-130. |
R831709 (2007) |
Exit |
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Locke E, Coronado GD, Thompson B, Kuniyuki A. Seasonal variation in fruit and vegetable consumption in a rural agricultural community. Journal of the American Dietetic Association 2009;109(1):45-51. |
R831709 (2007) |
Exit |
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Luderer U, Diaz D, Faustman EM, Kavanagh TJ. Localization of glutamate cysteine ligase subunit mRNA within the rat ovary and relationship to follicular apoptosis. Molecular Reproduction and Development 2003;65(3):254-261. |
R831709 (2005) R831709 (2007) |
Exit |
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Moreira EG, Yu X., Robinson JF, Griffith W, Hong SW, Beyer RP, Bammler TK, Faustman EM. Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos. Toxicology and Applied Pharmacology 2010;245(3):310-325. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) R834514 (Final) R834514C003 (Final) |
Exit Exit Exit |
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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) R831709 (2007) R831709C004 (2004) |
Exit Exit Exit |
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Ramaprasad J, Tsai MG, Fenske RA, Faustman EM, Griffith WC, Felsot AS, Elgethun K, Weppner S, Yost MG. Children's inhalation exposure to methamidophos from sprayed potato fields in Washington State:exploring the use of probabilistic modeling of meteorological data in exposure assessment. Journal of Exposure Science and Environmental Epidemiology 2009;19(6):613-623. |
R831709 (2007) R834514 (Final) R834514C002 (Final) |
Exit Exit |
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Richter RJ, Jampsa RL, Jarvik GP, Costa LG, Furlong CE. Determination of paraoxonase 1 status and genotypes at specific polymorphic sites. Current Protocols in Toxicology 2004;19(1):4. |
R831709 (2007) |
Exit |
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Richter RJ, Jarvik GP, Furlong CE. Determination of paraoxonase (PON1) status without the use of toxic organophosphate substrates. Circulation: Cardiovascular Genetics 2008;1(2):147-152. |
R831709 (2007) |
Exit Exit |
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Richter RJ, Jarvik GP, Furlong CE. Paraoxonase 1 (PON1) status and substrate hydrolysis. Toxicology and Applied Pharmacology 2009;235(1):1-9. |
R831709 (2007) R834514 (2012) R834514 (2013) R834514 (Final) |
Exit Exit Exit |
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Richter RJ, Jarvik GP, Furlong CE. Paraoxonase 1 (PON1) status as a risk factor for disease or exposure. Advances in Experimental Medicine and Biology 2010;660:29-35. |
R831709 (2007) |
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Robinson JF, Yu X, Hong S, Griffith WC, Beyer R, Kim E, Faustman EM. Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation. Toxicological Sciences 2009;107(1):206-219. |
R831709 (2007) |
Exit Exit |
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Robinson JF, Yu X, Hong S, Zhou C, Kim N, DeMasi D, Faustman EM. Embryonic toxicokinetic and dynamic differences underlying strain sensitivity to cadmium during neurulation. Reproductive Toxicology 2010;29(3):279-285. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) |
Exit Exit Exit |
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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) R831709 (2007) R831709C001 (2005) R831709C001 (2006) |
Exit Exit Exit |
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Snipes SA, Thompson B, O’Connor K, Godina R, Ibarra G. Anthropological and psychological merge:design of a stress measure for Mexican farmworkers. Culture Medicine and Psychiatry 2007;31(3):359-388. |
R831709 (2005) R831709 (2007) |
Exit |
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Stevens RC, Soelberg SD, Eberhart BT, Spencer S, Wekell JC, Chinowsky TM, Trainer VL, Furlong CE. Detection of the toxin domoic acid from clam extracts using a portable surface plasmon resonance biosensor. Harmful Algae 2007;6(2):166-174. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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Stevens RC, Suzuki SM, Cole TB, Park SS, Richter RJ, Furlong CE. Engineered recombinant human paraoxonase 1 (rHUPON1) purified from Escherichia coli protects against organophosphate poisoning. Proceedings of the National Academy of Sciences of the United States of America 2008;105(35):12780-12784. |
R831709 (2007) |
Exit Exit |
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Strong LL, Thompson B, Coronado GD, Griffith WC, Vigoren EM, Islas I. Health symptoms and exposure to organophosphate pesticides in farmworkers. American Journal of Industrial Medicine 2004;46(6):599-606. |
R831709 (2005) R831709 (2007) R831709C003 (2004) |
Exit |
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Strong LL, Thompson B, Koepsell TD, Meischke H. Factors associated with pesticide safety practices in farmworkers. American Journal of Industrial Medicine 2008;51(1):69-81. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C003 (2006) R831709C003 (2007) R832740 (Final) |
Exit Exit |
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Strong LL, Thompson B, Koepsell TD, Meischke H, Coronado GD. Reducing the take-home pathway of pesticide exposure:behavioral outcomes from the Para Niños Saludables study. Journal of Occupational and Environmental Medicine 2009;51(8):922-933. |
R831709 (2007) R834514 (Final) R834514C001 (Final) |
Exit |
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Suzuki SM, Stevens RC, Richter RJ, Cole TB, Park S, Otto TC, Cerasoli DM, Lenz DE, Furlong CE. Engineering human PON1 in an E. coli expression system. Advances in Experimental Medicine and Biology 2010;660:37-45. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) |
Exit |
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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. |
R831709 (2005) R831709 (2007) R831709C003 (2004) R826886 (2000) R826886C003 (2002) |
Exit Exit |
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Thompson B, Coronado GD, Vigoren EM, Griffith WC, Fenske RA, Kissel JC, Shirai JH, Faustman EM. Para niños saludables:a community intervention trial to reduce organophosphate pesticide exposure in children of farmworkers.Environmental Health Perspectives 2008;116(5):687-694. |
R831709 (2005) R831709 (2007) R831709C003 (2007) |
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Tiffany-Castiglioni E, Venkratraj V, Qian Y. Genetic polymorphisms and mechanisms of neurotoxicity:overview. Neurotoxicology 2005;26(4):641-649. |
R831709 (2007) R831709C002 (2004) |
Exit Exit Exit |
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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) R831709 (2007) R831709C004 (2005) R831709C004 (2006) |
Exit Exit Exit |
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VanDeMark KL, Guizzetti M, Giordano G, Costa LG. The activation of M1 muscarinic receptor signaling induces neuronal differentiation in pyramidal hippocampal neurons. Journal of Pharmacology and Experimental Therapeutics 2009;329(2):532-542. |
R831709 (2007) |
Exit Exit |
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VanDeMark KL, Guizzetti M, Giordano G, Costa LG. Ethanol inhibits muscarinic receptor-induced axonal growth in rat hippocampal neurons. Alcoholism, Clinical and Experimental Research 2009; 33(11):1945-1955. |
R831709 (2007) |
Exit |
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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) |
Exit Exit Exit |
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Wills AM, Landers JE, Zhang H, Richter RJ, Caraganis AJ, Cudkowicz ME, Furlong CE, Brown Jr. RH. Paraoxonase 1 (PON1) organophosphate hydrolysis is not reduced in ALS. Neurology 2008;70(12):929-934. |
R831709 (2007) |
Exit |
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Wong EY, Ponce RA, Farrow S, Bartell SM, Lee RC, Faustman EM. Comparative risk and policy analysis in environmental health. Risk Analysis 2003;23(6):1337-1349. |
R831709 (2005) R831709 (2007) |
Exit |
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Wong EY, Gohlke J, Griffith WC, Farrow S, Faustman EM. Assessing the health benefits of air pollution reduction for children. Environmental Health Perspectives 2004;112(2):226-232. |
R831709 (2005) R831709 (2007) |
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Young JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, Barr DB, Furlong CE, Holland NT. Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. NeuroToxicology 2005;26(2):199-209. |
R831709 (2005) R831709 (2006) R831709 (2007) R831709C002 (2004) R831709C002 (2006) R831710 (2004) R831710 (2005) R831710 (Final) |
Exit Exit Exit |
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Yu X, Sidhu JS, Hong S, Faustman EM. Essential role of extracellular matrix (ECM) overlay in establishing the functional integrity of primary neonatal rat Sertoli cell/gonocyte co-cultures:an improved in vitro model for assessment of male reproductive toxicity. Toxicological Sciences 2005;84(2):378-393. |
R831709 (2005) R831709 (2007) |
Exit Exit Exit |
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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) R831709 (2007) R831709C001 (2006) R832733 (2007) |
Exit Exit Exit |
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Yu X, Hong S, Faustman EM. Cadmium-induced activation of stress signaling pathways, disruption of ubiquitin-dependent protein degradation and apoptosis in primary rat Sertoli cell-gonocyte cocultures. Toxicological Sciences 2008;104(2):385-396. |
R831709 (2007) |
Exit Exit |
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Yu X, Robinson JF, Gribble E, Hong SW, Sidhu JS, Faustman EM. Gene expression profiling analysis reveals arsenic-induced cell cycle arrest and apoptosis in p53-proficient and p53-deficient cells through differential gene pathways. Toxicology and Applied Pharmacology 2008;233(3):389-403. |
R831709 (2007) |
Exit Exit Exit |
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Yu X, Hong S, Moreira EG, Faustman EM. Improving in vitro Sertoli cell/gonocyte co-culture model for assessing male reproductive toxicity:lessons learned from comparisons of cytotoxicity versus genomic responses to phthalates. Toxicology and Applied Pharmacology 2009;239(3):325-336. |
R831709 (2007) |
Exit |
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Yu X, Robinson JF, Sidhu JS, Hong S, Faustman EM. A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and ethylmercury in mouse embryonic fibroblast. Toxicological Sciences 2010;114(2):356-377. |
R831709 (2007) R834514 (2011) R834514 (2012) R834514 (2013) R834514 (Final) R834514C003 (Final) |
Exit Exit |
Supplemental Keywords:
children’s health, epidemiology, genetics, health risk assessment, risk assessment, assessment of exposure, asthma, children’s environmental health, diesel exhaust, environmental risks, exposure assessment, genetic mechanisms, genetic risk factors, genetic susceptibility, maternal exposure, nutritional risk factors, Environmental Management, Scientific Discipline, Health, RFA, Risk Assessment, Health Risk Assessment, Children's Health, Biochemistry, Environmental Chemistry, health effects, children's environmental health, assessment of exposure, developmental neurotoxicity, agricultural community, community-based intervention, pesticide exposure, genetic polymorphisms, biological response, environmental health, environmental risks, children's vulnerability
, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Biochemistry, Children's Health, Risk Assessment, environmental health, health effects, pesticide exposure, community-based intervention, developmental neurotoxicity, biological response, environmental risks, Human Health Risk Assessment, assessment of exposure, children's vulnerablity, genetic polymorphisms, children's environmental health
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).
R831709C001 Molecular Mechanisms of Pesticide-Induced Developmental Toxicity
R831709C002 Genetic Susceptibility to Pesticides
R831709C003 Community-Based Participatory Research Project
R831709C004 Pesticide Exposure Pathways Research Project
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.