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University of Washington Center for Child Environmental Health Risks Research

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University of Washington

Principal Investigator: Elaine Faustman, PhD

Elaine Faustman

Project 1: "Community-Based Participatory Research" Project 2: "Pesticide Exposure Pathways"
Project 3: "Molecular Mechanisms" Project 4: "Genetic Susceptibility"



Principal Exposures of Interest: Pesticides

Principal Outcomes of Interest: Physical and mental development, learning, mechanistic studies of toxicity, exposure, assessment and intervention

The theme of the Center for Child Environmental Health Risks Research (the Center) is to understand the mechanisms (molecular, genetic, age, exposure and environmental factors) that define children's susceptibility to pesticides, identifying the implications of this susceptibility for development and learning, and to partner with our communities to translate our findings into risk communication, risk management and public health prevention strategies.

The four research projects to be undertaken by the Center are closely linked by a common model. OPs will be examined in each project and researchers will share research results with one another through project-specific and Center-wide meetings. Two aspects of children's susceptibility to pesticides are addressed by the laboratory-based projects: the molecular mechanisms of neurotoxicity for OPs and the role of paraoxonase (PON1) in defining sensitivity of mammals to OPs. The two field-based research projects seek to increase our understanding of potential exposure pathways and the amounts of OPs to which children may be exposed, a key risk assessment issue for children in agricultural communities. In the CBPR project we will work with community groups and individuals to examine the pathways of potential OP exposure among adult/child pairs within the Yakima Valley region of Washington State. The Pesticide Exposure Pathways Research Project is designed to understand the potential for pesticide spray drift in agricultural communities.

Project 1: "Community-Based Participatory Research"
During the past 10 years, the Community-Based Participatory Research Project (CBPR) of our Center has worked with community groups and individuals to examine the take-home pathway of pesticide exposure among children of farmworkers in Yakima Valley. The CBPR study provided evidence that demonstrated children's exposure through a para-occupational pathway and in the previous 5 years of this Center grant, the CBPR Research Project conducted a community based inten/ention project (CIP) that identified and successfully implemented an intervention reducing the occupational take home pesticide exposure pathway for families and their children. These findings led to a number of additional questions on the part of our community partners; specifically, are there other pathways of pesticide exposure and are non-farmworkers exposed to pesticides. This proposed renewal project is designed to find answers to these questions. In this project, the CPBR investigators will characterize the seasonal variability of organophosphate (OP) exposure across our cohort by sampling at times of peak OP usage and by evaluating OP metabolite profiles across time during these seasons; assess the influence of gene environment interactions on OP exposure and response profiles; and calculate the contributions from gene, environment and season to within-person and between-person variability of the urinary OP metabolites in farmworkers to identify quantitatively differences between persons and across seasons.

Project 2: "Pesticide Exposure Pathways"
The overall objective of our research is to understand how exposures at a community scale, involving multiple applications, crops, weather patterns, and human activities may contribute to non-occupational exposures of children following pesticide applications. Pesticide drift and dispersion will be evaluated using measurements and physical transport models we have benchmarked in our previous studies to field samples from actual spray events. Residential characteristics and land use will be assessed with crop data and pesticide application information from the current decision tools used for selecting chemical treatments. Participant's activity patterns will be assessed using a GPS tracking device that can be integrated into a spatial-temporal data set describing personal activity during spray episodes. Using these physical and behavioral exposure factors, this study seeks to identify the determinants of children's exposure to pesticides from the proximity pathway as estimated through urinary metabolites or other biomarkers. This study will bring innovative methods of exposure assessment to bear on the problem of pesticide spray drift, and in doing so will identify the best opportunities for apphcator, community, or parental interventions.

Project 3: "Molecular Mechanisms"
This project will examine the relationship between AChE inhibition and neurotoxicity in depth, across pre- and postnatal developmental life stages. The overall hypothesis of our proposal is that pesticide exposure alters neurodevelopment and behavior in rodents by interfering with cellular pathways controlling proliferation, differentiation and apoptosis in the CNS during critical "windows of susceptibilty" and that these mechanisms are independent of AChE inhibition. Using in vitro neurodevelopmental-stage specific models for both pre and postnatal developmental periods, we propose to assess the role of OP-induced oxidative stress and its consequential impact on these important cellular pathways, which underlie CNS development.

Project 4: "Genetic Susceptibility"
The proposed studies aim to develop high throughput protocols for assessing OP exposures by characterizing specific biomarker proteins in blood, and to make use of these more accurate measures of exposure to investigate gene/environment interactions related to genetic variability in the paraoxonase (PONI) gene, particularly with respect to OP exposures that occur during early development.

Centers Funded By:
Centers Funded by Epa and NIEHS

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