The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estimates for a population of young farmworker children and to evaluate the model for chlorpyrifos and diazinon. Micro-activities of farmworker children collected concurrently with residential measurements of pesticides were used in the CACHED framework to simulate 115,000 exposure scenarios and quantify cumulative and aggregate exposure and dose estimates. Modeled metabolite urine concentrations were not statistically different than concentrations measured in the urine of children, indicating that CACHED can provide realistic biomarker estimates. Analysis of the relative contribution of exposure route and pesticide indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts for the largest dose, confirming the importance of the micro-activity approach. The risk metrics computed from the 115,000 simulations, indicate that greater than 95% of these scenarios might pose a risk to children's health from aggregate chlorpyrifos exposure. The variability observed in the route and pesticide contributions to urine biomarker levels demonstrate the importance of accounting for aggregate and cumulative exposure in establishing pesticide residue tolerances in food.
Keywords: children; farmworker; micro-activity; mixtures; organophosphate pesticides; physiologically-based pharmacokinetic; risk.