title: Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements.
abstract: Chlorpyrifos is a common agricultural insecticide and has been used residentially in the United States until the year 2000 when this use was restricted by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found in urine samples collected during exposure field studies. In this work, we use urinary biomarker data and the inverse solution of a simple pharmacokinetic (PK) model for chlorpyrifos to estimate the magnitude and timing of doses. Three urine samples were collected on separate days from each of 15 children (ages 3-12) who were participants in the Minnesota Children's Pesticide Exposure Study (MNCPES). The total volume of urine was noted and samples analyzed for TCPY: The urinary data was used along with constraints imposed on dose timing, based on responses of the individuals to pesticide-use surveys. We predicted the time and magnitude of multiple "event" exposures characterized by short-term, relatively high doses superimposed over a continuous background exposure. The average dose of chlorpyrifos predicted by the model was 1.61 microg/kg per reported event. Average background dose rate for these children that reported exposure events was 0.0062 microg/kg/h, or 0.15 microg/kg/day. In addition to predicting the total dose of chlorpyrifos received by an individual from urinary biomarker measurements, the model can then be run in a forward manner once the exposure regime is determined. This will allow the prediction of the total amount of TCPy eliminated in the urine over any time period of interest.
authors.affiliation: National Exposure Research Laboratory, U.S. Environmental Protection Agency, Las Vegas, Nevada 89193-3478, USA. rigas.marc@epa.gov
authors.forename: M L
authors.initials: ML
authors.lastname: Rigas
authors.forename: M S
authors.initials: MS
authors.lastname: Okino
authors.forename: J J
authors.initials: JJ
authors.lastname: Quackenboss
mesh_terms: D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D004390:Chlorpyrifos / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine*; D004781:Environmental Exposure / Q000032:analysis*; D006801:Humans; D008962:Models, Theoretical; D010575:Pesticides / Q000145:classification; D011237:Predictive Value of Tests; D011728:Pyridones / Q000032:analysis* / Q000652:urine; D011795:Surveys and Questionnaires; D013997:Time Factors; D014556:Urine / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D010575:Pesticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D004390:Chlorpyrifos