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

Chlorpyrifos is a common agricultural insecticide and has been used residen tially in the United States until the year 2000 when this use was restricte d by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos me tabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found in urine sample s collected during exposure field studies. In this work, we use urinary bio marker data and the inverse solution of a simple pharmacokinetic (PK) model for chlorpyrifos to estimate the magnitude and timing of doses. Three urin e samples were collected on separate days from each of 15 children (ages 3- 12) who were participants in the Minnesota Children's Pesticide Exposure St udy (MNCPES). The total volume of urine was noted and samples analyzed for TCPy. The urinary data was used along with constraints imposed on dose timi ng, based on responses of the individuals to pesticide-use surveys. We pred icted the time and magnitude of multiple "event" exposures characterized by short-term, relatively high doses superimposed over a continuous backgroun d exposure. The average dose of chlorpyrifos predicted by the model was 1.6 1 mug/kg per reported event. Average background dose rate for these childre n 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 indiv idual from urinary biomarker measurements, the model can then be run in a f orward manner once the exposure regime is determined. This will allow the p rediction of the total amount of TCPy eliminated in the urine over any time period of interest.