Abstract
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.
Highlights
Passage of the Food Quality Protection Act (FQPA) in 1996 required that in determining pesticide residue limits for food, the United States Environmental Protection Agency (US EPA) take into account the health risks associated with aggregate and cumulative pesticide exposure and incorporate an additional safety factor to protect children
The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) modeling framework was developed to represent the physical processes of exposure and dose through the incorporation of micro-activity time series, exposure mechanisms, and physiologically-based pharmacokinetic (PBPK)
Utilizing careful assumptions for exposure factors and age-specific physiological parameters, CACHED simulations completed with activity patterns and environmental concentrations collected from the same farmworker children population, resulted in realistic estimates of pesticide metabolite concentration in the children’s urine (Figure 3)
Summary
Passage of the Food Quality Protection Act (FQPA) in 1996 required that in determining pesticide residue limits for food, the United States Environmental Protection Agency (US EPA) take into account the health risks associated with aggregate (multiple route) and cumulative (multiple chemicals exhibiting a common mechanism of toxicity) pesticide exposure and incorporate an additional safety factor to protect children. Only the non-specific metabolites common to OPs are quantified in urine to provide a measure of exposure to this class of pesticides, but this does not provide levels of exposure to individual pesticides [4]. Methods are needed to quantify the contribution of each route and pesticide to the levels of non-specific biomarkers in urine and provide estimates of aggregate and cumulative dose, necessary for comparing to toxicological benchmarks like the US. Even for a widely studied chemical like chlorpyrifos, there is not a consensus on the appropriate absorption fractions for each route
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