Grantee Research Project Results

2005 Progress Report: 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.
Current 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)
Project Period Covered by this Report: May 1, 2005 through October 31, 2006
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Findings from the first 5 years of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study demonstrate that children often are 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 objectives of this research project are to: (1) examine the in vitro effects of pesticides (chlorpyrifos and maneb) and house dust mite allergen, 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; and (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.

Progress Summary:

Findings from this research include:

Immunological assessment was enhanced by high throughput analysis of 10 different cytokines (by Luminex and enzyme-linked immunosorbent assay [ELISA]) after combined treatment of blood cultures with combination of organophosphate pesticides and metabolites with endotoxin and dust mite allergen. For the first time, potentiation of cytokine response was demonstrated at low doses of chlorpyrifos in combination with endotoxin. This is an important observation because combined exposures to pesticides and endotoxin are typical for agricultural communities.
Analysis of cytokine profiles in children ages 12 and 24 months from the CHAMACOS cohort demonstrated increased variability in older children. Th1 was associated with parents work in agriculture, breastfeeding, and pets at home.
Two new enzymatic activities sensitive to inhibition by organophosphate pesticides independent of cholinesterase were found in red blood cells of CHAMACOS pregnant women and newborns. Characterization in respect to neurotoxicity is in progress.

Future Activities:

The investigators did not report any future activities.

Journal Articles:

No journal articles submitted with this report: View all 21 publications for this subproject

Supplemental Keywords:

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

Relevant Websites:

http://ehs.sph.berkeley.edu/chamacos Exit

Progress and Final Reports:

Original Abstract

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.