Grantee Research Project Results
2006 Progress Report: PON1 as a Predictor of Differential Susceptibility of Children to Organophosphate Pesticides
EPA Grant Number: R832734Title: PON1 as a Predictor of Differential Susceptibility of Children to Organophosphate Pesticides
Investigators: Eskenazi, Brenda , Barr, Dana Boyd , Holland, Nina T. , Hubbard, Alan , Bradman, Asa
Current Investigators: Eskenazi, Brenda , Barr, Dana Boyd , Bradman, Asa , Holland, Nina T. , Harley, Kim , Hubbard, Alan
Institution: University of California - Berkeley
EPA Project Officer: Callan, Richard
Project Period: March 20, 2006 through February 28, 2009 (Extended to February 28, 2011)
Project Period Covered by this Report: March 20, 2006 through February 28, 2007
Project Amount: $749,987
RFA: Early Indicators of Environmentally Induced Disease (2004) RFA Text | Recipients Lists
Research Category: Children's Health , Chemical Safety for Sustainability
Objective:
Organophosphate (OP) pesticide exposure is widespread in the U.S. population. Based primarily on animal studies, there is significant evidence that low-level exposure to OP pesticides can have adverse health effects in children (Eskenazi, et al., 2004; Young, et al., 2005). However, not all individuals may be equally susceptible. A gene, PON1, has been identified that may contribute to differential sensitivity to OP exposure. Our goal is to determine whether PON1 genotype and phenotype modify the association of OP pesticide exposure and neurodevelopmental outcomes in children.
Progress Summary:
This year, we finished blood collection, processing, and banking of samples from all 5-year-old children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (Eskenazi, et al., 2003). Collection in 7-year-old children and their mothers has begun this year. We conducted extensive validation experiments for PON1 enzyme activities on stored and freshly collected blood, established a range of variability for OPs in blood, and also performed DNA isolation for high-throughput genotyping from over 400 children and >500 mothers from the CHAMACOS cohort. Neurodevelopmental assessments were completed for 328 5-year-old children, for whom longitudinal data are also available (including the Brazelton and Bayley tests), and have also begun in 7-year-old children.
Future Activities:
We plan to complete enzyme activity assays in cord and child blood (5 years old) this year. These data will be used to determine whether PON1 genotype and PON1 activity are associated with child neurodevelopment (Specific Aim 2). Further validation experiments will be run at CDC to determine optimal volume and protocol for OP analysis in cord blood.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
| Other project views: | All 91 publications | 22 publications in selected types | All 22 journal articles |
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Eskenazi B. Centros de investigación de salud medioambiental y prevención de enfermedades de niños. Desde 1998 al presente. Acta Toxicologica Argentina 2006;14(Suppl):60-62. |
R832734 (2006) R831710 (2005) R831710 (Final) R831710C001 (2007) |
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Eskenazi B, Bradman A, Harley K, Holland N. Indicadores biologicos de exposicion a pesticidas y su relacion con la salud de los ninos. Acta Toxicologica Argentina 2006;14(Supplement):63-65. |
R832734 (2006) R831710 (2005) R831710C001 (2007) R831710C002 (2007) |
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Holland N, Furlong C, Bastaki M, Richter R, Bradman A, Huen K, Beckman K, Eskenazi B. Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns. Environmental Health Perspectives 2006;114(7):985-991. |
R832734 (2006) R832734 (2007) R832734 (Final) R831709 (2005) R831709 (2006) R831709 (2007) R831709 (Final) R831709C002 (2006) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2007) R831710C003 (2006) |
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Neri M, Bonassi S, Knudsen LE, Sram RJ, Holland N, Ugolini D, Merlo DF. Children’s exposure to environmental pollutants and biomarkers of genetic damage:I. Overview and critical issues. Mutation Research-Reviews in Mutation Research 2006;612(1):1-13. |
R832734 (2006) R832734 (2007) R832734 (Final) R831710 (Final) R831710C003 (2006) |
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Neri M, Ugolini D, Bonassi S, Fucic A, Holland N, Knudsen LE, Sram RJ, Ceppi M, Bocchini V, Merlo DF. Children’s exposure to environmental pollutants and biomarkers of genetic damage: II. Results of a comprehensive literature search and meta-analysis. Mutation Research-Reviews in Mutation Research 2006;612(1):14-39. |
R832734 (2006) R832734 (Final) R831710 (Final) R831710C003 (2006) |
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Supplemental Keywords:
PON1, organophosphates, pesticides, neurodevelopment,, Health, RFA, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Environmental Policy, Children's Health, Biochemistry, Genetics, Risk Assessment, Human Health Risk Assessment, pesticide exposure, genetic polymorphisms, susceptibility, human enzyme paraoxonase, children's vulnerablity, developmental neurotoxicity, assessment of exposure, farmworkers, gene-environment interaction, neurological developmentRelevant Websites:
http://ehs.sph.berkeley.edu/chamacos/ Exit
http://ehs.sph.berkeley.edu/Holland/Genomics/genomics.html Exit
Progress and Final Reports:
Original AbstractThe 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.