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Mechanisms of Pesticide Neuro and Immunotoxicity in Children Project
EPA Grant Number: R831710C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R831710
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: University of California Berkeley Center for Children’s Environmental Health Research
Center Director: Eskenazi, Brenda
Title: Mechanisms of Pesticide Neuro and Immunotoxicity in Children Project
Investigators: Holland, Nina , Casida, John , Lipsett, Michael , Tager, Ira
Current Investigators: Holland, Nina
Institution: University of California - Berkeley
EPA Project Officer: Fields, Nigel
Project Period: May 1, 2004 through October 31, 2008
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:Findings from the first five years of the Center’s CHAMACOS birth cohort study demonstrate that children are often exposed to mixtures of pesticides (maneb and chlorpyrifos) and allergens. These exposures may have synergistic, additive, or antagonistic effects on cell expression of key effect biomarkers. The specific aims of the Mechanism component of the Center will: 1) examine the in vitro effects of pesticides (chlorpyrifos and maneb) and house dust mite allergen (Der p1), alone and in combinations, on the production of Th1/Th2 cytokines; 2) determine whether pesticide and allergen exposures differentially affect cytokine expression in lymphocytes of children versus those of adults in vitro; 3) establish a new mechanism-based enzymatic assay for “neuropathy target esterase” (NTE) in human adult lymphocytes, 4) determine the ontogenetic changes in NTE activity in humans at different ages from birth to adulthood; 5) determine the sensitivities of NTE in children and adult lymphocytes to known NTE inhibitors, as well as to pesticides commonly found in our agricultural community in the Salinas Valley.
Approach:This project will take advantage of our large repository of biological samples from the CHAMACOS cohort of pregnant women and children. We will use in vitro cultures of human cells to examine the effects of individual and combined exposures to pesticides and allergens on the response of cytokine enzymes (a measure of inflammatory response). Cytokine dose responses will be determined by Taqman realtime PCR, flow cytometric detection of intracellular cytokines, and ELISA. Using these methods, we will elucidate mechanisms of pesticide-induced immunotoxicity, which may be related to respiratory disease in children. We will also examine the role of NTE activity in neurotoxity in a neuroblastoma cell line and in human lymphocytes using a new method based on interaction with a cellular target (lysophospholipids).
Expected Results:The cytokine dose-response studies will generate new information about the effects of pesticide exposures on the immune system and whether pesticide and allergen exposures interact synergistically, additively, or antagonistically. These data will further inform risk evaluation of low dose pesticide exposures to children and also identify key allergens that initiate immune responses that potentially lead to asthma. Finally, the NTE studies may have important clinical uses in assessing adverse health outcomes in cases of pesticide poisonings and chemical warfare and in understanding the mechanism of neurobehavioral effects of pesticide exposure in children.
Publications and Presentations:Publications have been submitted on this subproject: View all 14 publications for this subproject | View all 114 publications for this center
Journal Articles:Journal Articles have been submitted on this subproject: View all 4 journal articles for this subproject | View all 65 journal articles for this center
Supplemental Keywords:organophosphate, carbamate, dithiocarbamate, mixtures, allergen,
,
ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, PESTICIDES, Risk Assessment, Health Risk Assessment, Children's Health, Pesticide Types, exposure assessment, insecticides, allergen, health effects, respiratory problems, children's environmental health, assessment of exposure, childhood respiratory disease, outreach and education, agricultural community, community-based intervention, pesticide exposure, airway disease, environmental risks, immune system effects, environmental health hazard
Progress and Final Reports:
2004 Progress Report
2005 Progress Report
Main Center Abstract and Reports:
R831710 University of California Berkeley Center for Children’s Environmental Health Research
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831710C001 A Community-Based Participatory Research Project: CHAMACOS
R831710C002 Pesticide Exposure Assessment Project
R831710C003 Mechanisms of Pesticide Neuro and Immunotoxicity in Children Project
R831710C004 Community Outreach and Translation Core