![[logo] US EPA](https://webarchive.library.unt.edu/eot2008/20081105041528im_/http://www.epa.gov/epafiles/images/logo_epaseal.gif){kind=logo}
University of Washington Center for
Child Environmental Health Risks Research
Site Navigation
- Center Description
- Abstracts/Reports
- Publications
- Research Photos (PPT file)
- Washington Center Web Site
- Center One Pager (PDF, 1pp., 860KB, about PDF)
 |
Research Project Search
Principal Investigator: Elaine Faustman, PhD
| Overview | Selected Results |
| Exposures and Outcomes | Community Partners |
| Research Projects | Selected Publications |
The theme of the University of Washington based Center for Child Environmental Health Risks Research (CHC) is to understand 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 multi-disciplinary research center that takes advantage
of the established landscape of risk research at the University
of Washington; it is administratively housed within the Institute
for Risk Analysis and
Risk Communication that
is in the UW's
School of Public Health and Community Medicine . The inter-disciplinary
nature of the CHC allows researchers from various academic backgrounds
to work together to reduce the effects of environmental pesticide
exposure in children. Research ranges from the basic to the
applied, and includes toxicology, exposure assessment and community
intervention. The CHC includes partnerships with agricultural
communities in the Yakima Valley of central Washington. This
work, to jointly accomplish pesticide intervention, reduces childhood
pesticide exposures.
Two major topics of study are assessment of environmental impacts
on childhood learning and environmental effects on growth and development.
The Center incorporates scientific findings on pesticide toxicity
and exposure into its risk assessment models, making the models
protective of children's health.
Children are not just small adults. Because their bodies and
minds are still developing, children are more susceptible than adults
to the effects of pesticides.This was first established in the National
Research Council's 1993 report "Pesticides
in the Diets of Infants and Children." Yet even today,
most risk assessments for environmental agents don't account for
this fact. CHC research into the biochemical, molecular and exposure
mechanisms that underlie children's susceptibility to pesticides,
will help develop new models for assessing pesticide risks to normal
development and learning.
Exposures and Outcomes
Primary Exposures: Agricultural pesticides.
Primary Outcomes: Children’s behavior patterns and neurodevelopment, pesticide exposure reduction strategies.
Research Projects
The CHC comprises two laboratory-based research projects, two field-based projects, and four facility cores.
The specific objectives of the laboratory-based research projects are:
- to identify cellular, biochemical and molecular mechanisms for the adverse developmental neurotoxicity of pesticides and
- to identify the impact of genetic polymorphisms for the enzyme paraoxonase on the developmental neurotoxicity of organophosphate pesticides.
Researchers are utilizing the expertise in the Center's Neurobehavioral Assessment Facility Core to assess what effects pesticide exposure may have on children's behavior patterns and development.
The specific objectives of the two field based projects — a pesticide exposure pathways research project plus the related community based intervention study — are:
- to identify critical pathways of pesticide exposure for children; and
- to develop a culturally-appropriate intervention to break the take-home pathway that will ultimately result in reducing children's exposure to pesticides.
The four facility cores (Neurobehavioral Assessment, Exposure Assessment, Risk Characterization and Community Outreach & Translation) 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.
Original Projects: 1998-2003
Project 1: Molecular Mechanisms of Pesticide Induced Developmental Neurotoxicity - Cellular and Molecular Aspects of Pesticide Neurodevelopmental Toxicity
The Molecular Mechanisms Research Project specifically evaluated 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.
Researchers investigated two of the most commonly used organophosphate pesticides — chlorpyrifos and diazinon — as well as persistent pesticides that were used historically, focusing 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.
Project 2: Genetic Susceptibility to Pesticides/Paraoxonase Polymorphism: Role in Neurodevelopmental Susceptibility to Organophosphates
The Paraoxonase Polymorphism (PON-1) Study 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 (PON-1) in protecting against developmental neurotoxicity.
Recent studies in humans (run in collaboration with the UC-Berkeley CHAMACOS) have shown that developmental onset of PON-1 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 PON-1 to pesticide toxicity has had profound effects for understanding human health and now its role in defining children’s susceptibility is under investigation.
Project 3: Community-Based Participatory Research Project – Reducing Take-Home Pesticide Exposures in Children of Farmworkers in Yakima Valley, Washington
The overall goal of the Community Intervention Project (CIP) is to investigate multiple pathways that may contribute to pesticide exposure in adults and children living in agricultural communities.
The Community Intervention Project utilizes the results of the Pesticide Exposure Study and is evaluating the impact of modifying the occupational take-home exposure pathway on children's exposure to pesticides. These two studies together are evaluating pesticide exposures in children of farmworkers with the overall aim of reducing pesticide exposures in children. Given the complexity of children's exposure to pesticides, the Pesticide Exposure Study will estimate the relative' contribution of major pesticide exposure pathways for children of farmworkers. The long-term objective is to prioritize efforts to prevent childhood pesticide associated illness. The Exposure Assessment Core will be critical to this project as they will develop source attribution models for the major exposure pathways.
In previous studies at UW, the worker take-home exposure pathway has been identified as an important pesticide exposure pathway for children; the Community Intervention Project will evaluate the effect of breaking this pathway. Information on what intervention strategies work in agricultural communities to reduce children's exposure to pesticides is critical for our national child health promotion goals. The CHC is poised to apply its extensive experience in basic and field based research, and its vast experience working with the public on public health issues, to meet the challenge of improving children's health.
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.
Project 4: Pesticide Spray Drift Study: Pesticide Exposure Pathways for Farmworkers'Children in Yakima Valley, Washington
The overall objective of this project was to understand the underlying physical and behavioral mechanisms by which non-occupational exposure occurs following pesticide applications.
The study measured airborne concentrations of pesticides in a community during and after a spray event and investigated assumptions that are made to ensure the safe application of pesticides. Results revealed that the existing volatilization model underpredicted (by about 4-fold) the measured pesticide concentration after the spray event when temperatures rose significantly. This indicates a need to reexamine inhalation exposures for pesticides when the temperature is high. Further, when linked with the study examining children’s activity profiles, the spray drift study suggests a need to reevaluate transport modeling and exposure factors.
Current Projects: 2003-2008
Project 1: Genetic Susceptibility to Pesticides
Lucio G. Costa, Study Director
This project examines the role of genetic variability in the polymorphic serum enzyme paraoxonase (PON1) in protecting against developmental neurotoxicity associated with pesticides. Recent studies in humans have shown that developmental onset of PON1 is highly variable among children. It can appear at ages as early as 4 months and as late as 2 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. As highlighted by the National Institute of Environmental Health Sciences Director, David Schwartz, the contribution of PON1 to pesticide toxicity has had profound effects on human health and now its role in defining children’s susceptibility is under investigation.
The objective of this research project is to identify susceptibility factors for developmental neurotoxicity of pesticides, including genetic polymorphisms. The overall aim is to investigate the developmental neurotoxicity of two of the most commonly used organophosphates: chlorpyrifos and diazinon. Researchers will also determine the role of genetic variability in the polymorphic serum enzyme paraoxonase (PON1) in protecting against developmental neurotoxicity.
Specific Aims:
- Acute toxicity/dose finding by establishing a dosage regimen, determining the acetylcholinesterase (AChE) inhibition associated with these dosages, and investigating the relative contributions of chronic low-level exposure and single-dose exposures to AChE inhibition.
- Investigate the developmental neurotoxicity of chlorpyrifos following chronic postnatal exposure.
- Investigate the developmental neurotoxicity of diazinon following postnatal exposure.
- Compare the developmental neurotoxicity of chlorpyrifos and diazinon to directly assess the similarities and differences in toxicity that are associated with exposure to these two related compounds, and the involvement of the Q192R polymorphism in modulating sensitivity to these effects.
Project 2: Pesticide Exposure
Pathways Research Project
Michael Yost, Project Director
The Pesticide Exposure Pathways Project uses environmental modeling,
environmental sampling, child activity analysis, biological monitoring
and aerial photography analysis to characterize pesticide spray
drift deposition as an exposure pathway for young children living
in agricultural communities. The objective is to improve
our understanding of critical pathways of pesticide exposure
for children.
You can download a poster to
read more detailed information about this research.
Specific Aims
The Pesticide Exposure Pathways researchers combine novel methods for studying children’s activity patterns with expertise in ambient monitoring of pesticide residues and modeling of transport processes. The specific research aims are:
- Examine aerial spraying of organophosphates on potatoes in the Columbia Basin of Washington and on winter cultivation sites in the lower Rio Grande Valley in South Texas and to compare spray drift patterns, housing types and human activity patterns in these varying climatic conditions (hot/dry in eastern WA and cool/dry in southern TX).
- Investigate drift from air-blast applications compared to aerial applications in Chelan and Douglas counties, Washington and to examine the pesticide penetration through the canopy cover and the terrain effects on drift.
- Analyze satellite images of the Yakima valley to identify crop type and location.
Pesticide Exposure Pathways Project at the University of Washington’s Center for Child Environmental Health Risks Research uses environmental modeling, environmental sampling, child activity analysis, biological monitoring and analysis of aerial photography to characterize the exposure pathways for children living in agricultural communities.
Project 3: Molecular Mechanisms of Pesticide-Induced
Developmental Toxicity
Elaine Faustman, Study Director
The overall aim of this project is to evaluate the molecular and cellular mechanisms through which specific pesticides cause neurodevelopmental toxicity, and to define the "windows of susceptibility" for these neurotoxicants.
The Center is investigating two of the most commonly used organophosphate pesticides (OP), chlorpyrifos and diazinon, as well as persistent pesticides that were used historically. Researchers 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 and Biologically Based Dose Response models. This approach allows for evaluation of the mechanisms of action, including gene environment interactions, cell cycle regulation, and oxidative stress. A systems biology approach that our Center employs leads to an integrated understanding of the critical pesticide exposures associated with neurodevelopmental toxicity.
You can download a poster to
read more detailed information about this research.
Specific Aims
- Evaluate the mechanism of action through which pesticides affect neurogenesis versus gliogenesis.
- Evaluate the contribution of specific cell cycle control checkpoint pathways in defining susceptibility of neurons and glial cells to pesticide induced effects on proliferation.
- Evaluate the role that specific stress-activated cell signaling pathways (p38 MAPK, SAPK/JNK) play in mediating pesticide induced effects on viability, proliferation, and apoptosis in neuronal and glial cells.
- Evaluate the role that reactive oxygen species (ROS) generation and antioxidant machinery play in defining susceptibility to pesticide-induced neurodevelopmental toxicity.
Project 4: Community-Based Participatory Research – Reducing
Take-Home Pesticide Exposures in Children of Farmworkers in
Yakima Valley, Washington
Beti Thompson,
Project Director
This project investigates the multiple pathways that contribute
to children's pesticide exposure in an agricultural community.
The objectives of the research project are to: (1) intervene to reduce
children’s exposure to pesticides, including the development of a culturally
appropriate intervention to break the take-home pathway; and (2) 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 community-based participatory 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.
As a result of receipt of donor funds, we were able to increase the scope of
work for this research project to include collection of additional biological
specimens that will enhance the project further. The additional tasks include: (1)
comparing the levels of organophosphorus pesticide (OP) parent compounds in the
blood of adult farmworkers and non-farmworkers, adjusting for the multiple pathways;
(2) compare levels of pesticide residues in saliva to those in urine and blood
to determine reliability and validity of data and to assess more accurately the
presence of Ops; (3) conduct blood analysis through finger sticks to ascertain
cholinesterase levels; and (4) conduct analysis of buccal cell samples in adults
and children of farmworkers and non-farmworkers to gain a better understanding
of the mechanisms of toxicity of OPs.
The research questions for this project were driven by the Community Advisory
Board (CAB), which is deeply interested and involved in ongoing research on pesticides.
The CAB is a model of community-based participatory research and ensures that
all aspects of the research are conducted with integrity and in a timely manner.
You can download a poster to
read more detailed information about this research.
Click here to
download educational materials from For Healthy Kids!/¡Para
Niños Saludables!, provided to the CHC intervention
group.
Specific Aims
To examine four main pathways of potential exposure to OP pesticides:
- A take-home pathway resulting from pesticide residues on clothing, skin, and boots that accumulate as a result of working in fields;
- A dietary pathway that emphasizes the intake of foods that may contain pesticides, such as fruits and vegetables;
- An environmental pathway that includes proximity of family homes and play areas to spray or spray drift areas; and
- A lifestyle pathway that includes practices used by adults to protect their children from pesticide exposures.
Environmental Public Health Continuum
- Researching genetic links. Paraoxonase (PON1), a polymorphic enzyme, has been shown to be a major factor in determining susceptibility to the toxicity of certain organophosphorus (OP) insecticides. Utilizing different approaches, including transgenic animal models, CHC researchers have been able to show that PON1 plays even a more important role in young children, as they have a very low level of this enzyme. See for example: (Cole et al. 2003; Cole et al. 2005; Furlong et al. 2006).
- Developing novel methods. Methods development in the Center included new approaches for characterizing children’s activity patterns using GPS technology and use of laser based real-time measurement of pesticide spray drift. New mechanistic tools have also been developed including development of “humanized transgenic animal models” (See Cole et al, 2005), innovative new in vitro techniques with neuronal precursor cells (Gribble, 2005), and techniques for in vivo mouse neurobehavioral studies. The Center’s interdisciplinary structure has sparked three new statistical and modeling approaches relevant both for Center studies but also highly important for general approaches for understanding impacts during early development.
- Communicating results. The CHC has been involved in a long list of activities to translate and communicate our research results. This communication strengthened the scientific design of our studies, as a result of community and stakeholder interactions. For example, on the suggestion of the Community Advisory Board (CAB), researchers added assessment of pesticide levels in vehicle dust to the occupational take-home exposure pathways study design. This additional data later proved to be instrumental in linking the agricultural occupational take home exposure patterns through correlations with both house dust and children’s urinary pesticide metabolites. In addition, the interest of the CAB in warehouse workers and their exposures resulted in the design of our warehouse worker study.
- Testing complex hypotheses. Because the CHC is an interdisciplinary effort, researchers have been able to use a risk assessment framework (Faustman et al. 2000) to integrate molecular mechanistic research with biomarkers of exposure and genetic susceptibility, test these hypotheses in the field, and directly assess translation via assessment of community and individual interventions.
- Linking science and risk assessment needs. Because our Center is built around a risk assessment framework we are able to link findings on pesticide exposure and kinetics to improve our ability to predict outcomes using innovative toxicokinetic and toxicodynamic modeling techniques. Our lab-based projects investigate the mechanisms of susceptibility during three critical stages of brain development, genetic and age-dependent variations in susceptibility, and functional assessments of exposure. In order to link these observations with our environmental and community pesticide exposure studies we needed toxicokinetic and toxicodynamic models. These models were developed by the Center researchers.
- Building capacity for children’s environmental health. Our Center’s impact has been magnified through critical activities, including: training a new generation of scientists in children’s environmental health sciences, educating pediatricians and other health professionals, regional, national and international outreach and translation activities, and leveraging center capacity for new research opportunities.
The Center for Child Environmental Health Risks Research works with a large
number of community partners. The Community-based Participatory Research project
is advised by a Community Advisory Board (CAB) which consists of farmworkers,
growers and representatives from the Farm Workers
Union, the Growers’ Association,the Department
of Health, the Department of Agriculture,
the Yakima Valley Farm Workers Clinics,
the local Spanish radio station (Radio KDNA),
Washington State Department of Labor and Industries, Columbia
Legal Services,
and the local office of the Environmental
Protection Agency. The CBPR has also enlisted local organizations such
as the Farm Workers Union ,
the Washington
State Migrant Council,
and the Growers’ Association to
help in outreach.
Other partnerships come through the Center’s connection to
the University of Washington. One of the strongest links is with
the University of Washington NIEHS Center
for Ecogenetics and Environmental Health’s (CEEH) Community Outreach
and Education Program (COEP) . The
Center has partnered with COEP to develop child health relevant materials.
Collaboration with Counseling
and Advice on Reproductive Exposures (CARE) Northwest has
identified child-relevant risk communication issues. In addition,
the UW Children’s Center participated in a Town Meeting hosted by CEEH
in Autumn 2000. The Town Meeting brought together community members throughout
Washington State to talk about environmental health concerns such as those
related to agricultural pesticide use. The Center maintains a strong
link to the NIEHS/CDC-funded Pacific
Northwest Agricultural Safety and Health Center (PNASH) .
Several PNASH projects have leveraged funding to focus on children’s
exposure to pesticides, exposure to lead and arsenic in orchard soils,
children health, and farm safety in teens. The Center continues to
coordinate and look for joint projects with PNASH, especially relating
to agricultural issues. The Center also collaborated with the Washington
Kids Count Program ,
a project of the Human Services Policy Center in the UW Evans School of
Public Affairs. WA Kids Count released the 2002 County and City Profiles
of Child and Family Well-Being in December 2002.
Cole
TB, Jampsa RL, Walter BJ, Arndt TL, Richter RJ, Shih DM, Tward A,
Lusis AJ, Jack RM, Costa LG, and Furlong CE 2003. Expression
of human paraoxonase (PON1) during development. Pharmacogenetics.
June, 2003; 13(6): 357-364.
Coronado GD, Thompson B, Strong L, Griffith WC, Islas I 2004. Agricultural task and exposure to organophosphate pesticides among farmworkers. Environ Health Perspect. 2004 Feb;112(2):142-7. Comment in: Environ Health Perspect. 2004 Nov;112(15):A865-6; author reply A866. Environ Health Perspect. 2004 Sep;112(13):A724-5; author reply A725-6.
Coronado GD, Vigoren EM, Thompson B, Griffith WC, Faustman EM 2006. Organophosphate pesticide exposure and work in pome fruit: evidence for the take-home pesticide pathway. Environ Health Perspect. 2006; 114(7): 999-1006.
Costa LG, Cole TB, Vitalone A, and Furlong CE 2005. Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clin Chim Acta. Feb 2005; 352(1-2): 37-47.
Elgethun K, Fenske RA, Yost MG, Palcisko GJ 2003. Time-location analysis for exposure assessment studies of children using a novel global positioning system instrument. Environ Health Perspect. Jan, 2003; 111(1): 115-22.
Faustman E, Silbernagel S, Fenske R, Burbacher T, and Ponce R 2000. Mechanisms underlying children's susceptibility to environmental toxicants. Environ Health Perspect. 2000; 108 Suppl 1: 13-21.
Furlong CE, Cole TB, Jarvik GP, Pettan-Brewer C, Geiss GK, Richter RJ, Shih DM, Tward AD, Lusis AJ, Costa LG 2005. Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants. Neurotoxicology. 2005 Aug;26(4):651-9.
Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B 2006. PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenet Genomics. March, 2006; 16(3): 183-190.
Gohlke JM, Griffith WC, Faustman EM 2007. Computational Models of Neocortical Neuronogenesis and Programmed Cell Death in the Developing Mouse, Monkey, and Human. Cerebral Cortex. 2007 Jan 4; [Epub ahead of print]
Gohlke JM, Griffith WC, Faustman EM 2005. A systems-based computational model for dose-response comparisons of two mode of action hypotheses for ethanol-induced neurodevelopmental toxicity. Toxicol Sci. 2005 Aug;86(2):470-84. Epub 2005 May 25.
Judd NL, Drew CH, Acharya C, Mitchell TA, Donatuto JL, Burns GW, Burbacher TM, Faustman EM 2005. Framing Scientific Analyses for Risk Management of Environmental Hazards by Communities: Case Studies with Seafood Safety Issues. Environ Health Perspect. 2005 Nov;113(11):1502-8.
Thompson B, Coronado GD, Grossman JE, Puschel K, Solomon CC, Islas I, Curl CL, Shirai JH, Kissel JC, Fenske RA 2003. Pesticide take-home pathway among children of agricultural workers: study design, methods, and baseline findings. J Occup Environ Med. 2003 Jan;45(1):42-53.
Weppner S, Elgethun K, Lu C, Hebert V, Yost MG, Fenske RA 2006. The Washington aerial spray drift study: children's exposure to methamidophos in an agricultural community following fixed-wing aircraft applications. J Expo Sci Environ Epidemiol. 2006 Sep;16(5):387-96.
Full
List of Publications | Publications
List from NIEHS PubMed Database
Centers Funded By: 