2002 Progress Report: Saliva Bio-monitoring for Organophosphorus Pesticide Exposures in Children

EPA Grant Number: R828606
Title: Saliva Bio-monitoring for Organophosphorus Pesticide Exposures in Children
Investigators: Fenske, Richard , Lu, Chun
Current Investigators: Fenske, Richard , Barr, Dana Boyd , Lu, Chensheng (Alex) , Rodriguez, Teresa
Institution: University of Washington - Seattle
Current Institution: University of Washington - Seattle , Centers for Disease Control and Prevention , Emory University , Universidad Nacional Autónoma de Nicaragua–León
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2000 through August 31, 2003 (Extended to August 31, 2005)
Project Period Covered by this Report: September 1, 2001 through August 31, 2002
Project Amount: $742,597
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2000) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health


The overall objective of this research project is to evaluate the feasibility of quantifying children's exposure to organophosphorus (OP) pesticides through saliva biomonitoring. This work is part of an ongoing effort to improve exposure assessment methods for children. Two OP pesticides-chlorpyrifos and diazinon-are proposed for this study. These compounds are widely used in both agricultural and residential environments, and the resulting aggregate exposures for children are complex, and therefore, amenable to biological monitoring. The specific objectives of the research project are to: (1) determine the pharmacokinetics of these pesticides in saliva and plasma in animals following dermal and oral dosing at variable exposure levels and salivary flow rates; (2) characterize the relationship of pesticide concentrations in saliva and plasma in animals, and evaluate the sensitivity and specificity of salivary excretion for these two compounds at low doses; (3) modify and validate ELISA methods for analyzing chlorpyrifos and diazinon in biological samples; (4) measure children's exposures to chlorpyrifos and diazinon in saliva and urine following the application of these compounds in nearby orchards or within residences; (5) develop a pharmacokinetic model for these pesticides in children using salivary and urinary measurements; and (6) compare total absorbed dose estimates for diazinon and chlorpyrifos in children using salivary measures of parent compounds, urinary dialkylphosphate metabolite measurements, and compound-specific urinary metabolite data.

Progress Summary:

Several objectives were accomplished in Year 2 of the project. We have finalized the animal surgical procedures, particularly the delivery solution. We used Intralipid 20 percent intravenous fat emulsion as the mixing solution, with pesticides for intravenous injection. Intralipid has been widely used in clinical settings for human use, and it appears to be safe for our study. We successfully resolved the ELISA problems by adding a sample clean-up procedure in the standard operating procedure. We were able to recover approximately 80 percent of diazinon from the spike matrices using ELISA. We have completed the analysis of saliva and plasma samples collected from the diazinon study. This data set has been analyzed using SAAM II, mathematical software for pharmacokinetic analysis of biological data. Alex Lu has attended two workshops on how to use the software to create pharmacokinetic models for the data set. The results of the diazinon study have been written into a manuscript and submitted to a peer-reviewed journal. We are finalizing the chlorpyrifos study in animals, and will be writing another manuscript for chlorpyrifos data. We decided to expand the list of interested pesticides in this grant by adding permethrin, one of the most commonly used synthetic pyrithroid insecticides. We obtained approval for this addition from the Project Officer in May 2002. Currently, we are validating the feasibility of monitoring permethrin levels in animal saliva. We have obtained a fairly new ELISA assay from Dr. Bruce Hammock's laboratory at University of California-Davis (UC Davis) for the permethrin study. We are in the process of determining the recovery of permethrin from saliva and plasma using this ELISA assay.

Future Activities:

Future activities involve our continued effort to validate the feasibility of saliva biomonitoring in animals for chlorpyrifos and permethrin. We anticipate completing the animal study by April 2003.

We have identified a group of children whom we believe to be exposed to high levels of chlorpyrifos. We will be collecting saliva and urine samples from children to determine their exposures. We also will collect saliva and venous blood from the children's parents to determine the relationship of chlorpyrifos concentrations in saliva and in plasma. We anticipate this to begin in June 2003.

We also are working with investigators at UC Davis to collaborate with a study in which saliva, blood, and urine will be collected simultaneously from humans. The Institutional Review Board at UC Davis already approved the protocol. We anticipate this collaboration to start in September 2003.

Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other project views: All 8 publications 3 publications in selected types All 3 journal articles
Type Citation Project Document Sources
Journal Article Lu C, Irish R, Fenske R. Biological monitoring of diazinon exposure using saliva in an animal model. Journal of Toxicology and Environmental Health-Part A 2003;66(24):2315-2325. R828606 (2002)
R828606 (2003)
R828606 (Final)
  • Abstract from PubMed
  • Supplemental Keywords:

    biomarker, biomonitoring, organophosphorus, OP, OP pesticides, permethrin, diazinon, chlorpyrifos, saliva, plasma, children., RFA, Health, Scientific Discipline, Toxics, Environmental Chemistry, Health Risk Assessment, pesticides, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Environmental Monitoring, Children's Health, genetic susceptability, pesticide exposure, sensitive populations, infants, dermal contact, exposure, chlorpyrifos, air pollution, children, survey, insecticides, pesticide residues, toxicity, children's vulnerablity, exposure pathways, saliva, biological markers, dietary exposure, Diazinon, exposure assessment, organophosphate pesticides

    Relevant Websites:

    http://depts.washington.edu/pnash Exit
    Synthesis Report of Research from EPA’s Science to Achieve Results (STAR) Grant Program: Feasibility of Estimating Pesticide Exposure and Dose in Children Using Biological Measurements (PDF) (42 pp, 3.87 MB)

    Progress and Final Reports:

    Original Abstract
  • 2001 Progress Report
  • 2003 Progress Report
  • 2004
  • Final Report