Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements

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 mug/kg per reported event. Average background dose rate for these children that reported exposure events was 0.0062 mug/kg/h, or 0.15 mug/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.