Development of a model to estimate aggregate and cumulative exposure and dose in young children.

摘要

While considerable attention has been placed on identifying sources of pollution and resulting health effects, knowledge of human exposure and dose is limited for most toxins. To provide more robust estimates, a physical-stochastic model (Stanford Protocol for Estimating Exposure and Dose (SPEED), has been developed to quantify exposure and dose for multiple routes and various pesticides with a common mechanism of toxicity. Based on previous models, SPEED integrates micro-level activity time series (MLATS), exposure mechanisms and physiologically based pharmacokinetic (PBPK) components. Contributions include modules to estimate dietary exposure, gastrointestinal absorption, and a full body PBPK model for parent pesticides and metabolites capable of accounting for changes in physiology as a function of age and gender. SPEED's unique incorporation of MLATS, sequential records of hand and mouthing contacts, allows for a more physically representative estimation of dermal and non-dietary ingestion exposure and facilitates the identification of exposure-prone behaviors and their contribution to absorbed dose.; SPEED was evaluated by quantifying cumulative aggregate exposure and dose to farmworker's children (6-27 months old). MLATS collected concurrently with residential measurements of pesticides were used to simulate 115,000 exposure scenarios. Target chemicals were organophosphate pesticides (i.e., chlorpyrifos and diazinon) because of their widespread use, common mechanism of toxicity and density of data. Dermal exposure simulations were within a factor of 2 of measured values from dosimeters worn by the children. Modeled urine metabolite concentrations were not statistically different than measured values from children in the same population.; Route and pesticide contribution analysis indicates that in general, chlorpyrifos dietary exposure accounts for the largest portion of metabolites in urine, however much variability was observed in route and pesticide contribution among the simulated data. Non-dietary ingestion exposure also contributed substantially to children's aggregate dose for both pesticides, and positive correlations established between dose and mouthing activity confirms the importance of the "micro-activity" approach. The risk metrics computed aggregate chlorpyrifos exposure simulations indicate that greater than 90% of these scenarios might pose a risk to children. SPEED can be adapted in the future to estimate exposure and dose from other chemicals.