Grantee Research Project Results

Center for Children’s Environmental Health Research – Mechanisms of Pesticide Neuro- and Immunotoxicity

EPA Grant Number: R831710C003
Subproject: 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: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Center for Children’s Environmental Health Research – Mechanisms of Pesticide Neuro- and Immunotoxicity
Investigators: Holland, Nina T. , Tager, Ira , Lipsett, Michael , Casida, John
Institution: University of California - Berkeley
EPA Project Officer: Callan, Richard
Project Period: May 1, 2004 through October 31, 2008 (Extended to October 31, 2010)
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health

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 21 publications for this subproject | View all 170 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 13 journal articles for this subproject | View all 136 journal articles for this center

Supplemental Keywords:

organophosphate, carbamate, dithiocarbamate, mixtures, allergen,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, PESTICIDES, Health Risk Assessment, Children's Health, Pesticide Types, Risk Assessment, health effects, pesticide exposure, community-based intervention, immune system effects, airway disease, environmental risks, respiratory problems, Human Health Risk Assessment, insecticides, assessment of exposure, childhood respiratory disease, environmental health hazard, children's environmental health, outreach and education, agricultural community, allergen

Progress and Final Reports:

Main Center Abstract and Reports:

R831710 Center for Integrative Research on Childhood Leukemia and the Environment - 2015

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831710C001 Center for Children’s Environmental Health Research – CHAMACOS Community Based Research Project
R831710C002 Center for Children’s Environmental Health Research – Pesticide Exposure Assessment Project
R831710C003 Center for Children’s Environmental Health Research – Mechanisms of Pesticide Neuro- and Immunotoxicity
R831710C004 Center for Children’s Environmental Health Research – Community Outreach and Translation Core

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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.