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USE OF PHARMACOKINETIC MODELING FOR DIETARY EXPOSURE STUDY DESIGN AND MODEL EVALUATION
Citation:
Hu, Y., E. D. Pellizzari, G G. Akland, L J. Melnyk, AND M Berry. USE OF PHARMACOKINETIC MODELING FOR DIETARY EXPOSURE STUDY DESIGN AND MODEL EVALUATION. Presented at ISEA Annual Meeting, Vancouver, British Columbia, August 11, 2002.
Impact/Purpose:
The purpose of this research is to reduce uncertainties in exposure assessments of young children by improving EPA's ability to measure exposures in the context of aggregate and cumulative exposure assessments. The general objective of this research is to support FQPA children's exposure assessment efforts by improving procedures and reducing uncertainty in measurements for dietary exposure of young children, a critically needed area for improved risk assessment. Specifically, this research will evaluate a protocol and companion model for measuring or otherwise assessing the combined dietary intake of a young child as influenced by pesticides, or other environmental contaminants, which contaminate their foods during the eating process (indirect ingestion exposure). This research will continue to develop the important factors which are needed to characterize excess intake of pesticides by young children. Specifically, the research will measure pesticide surface transfer efficiencies for food contacts with surfaces and eating activity patterns of young children that define the frequency of contacts with contaminated surfaces. A series of reports/products are anticipated by the end of FY05.
Description:
It has been shown that young children have potentially higher dietary pesticide intake when they handle foods while eating. Foods become contaminated with pesticides from "dirty" hands and home surfaces. A dietary intake model has been developed to estimate the potential increase in pesticide exposure caused by food handling and the model prediction has been confirmed in the small-scale field study. However, modelers often struggle with the validity of models and often model validation using biomarkers is unsuccessful because of large intra- and inter- individual variabilities for exposures, metabolism, physiological parameters, multiple sources of the exposures, and laboratory measurement errors. In this work, we demonstrated how to efficiently conduct a field study with the appropriate study design guided by pharmacokinetic modeling to minimize these problems. We used the children's dietary exposure model to evaluate increased pesticide intakes. Our work indicated that a longitudinal study in which the subject can serve as his/her own control, proper selection of pesticides with a biological half-life in appropriate range, and homes with pesticide loadings at specified levels were important factors to design a successful field study to evaluate the children's dietary intake model. We also explored the effects of other exposure pathways such as exposures via inhalation and indirect ingestion from non-dietary sources to evaluate the model using urinary biomarkers.
We attempted to evaluate the dietary pesticide intake model using two methods: the left-over foods and urinary measurements in a small-scale longitudinal study that involved 3 young children. Exposed days that allowed normal dietary exposure caused by handling of the foods alternated with unexposed days to create a predicted zig-zag pattern in the urinary pesticide metabolite measurements. The left over food measurements demonstrated that the handled foods indeed had much higher pesticides than foods that were not handled by the children (P=0.007). The zig-zag pattern predicted by toxicokinetic modeling was also observed in actual urinary metabolite measurements of all of the 3 subjects, which indicates an observable increase in dietary pesticide intake caused by children's handling of the foods. Comparison of the predicted urinary measurements and actual measurements, however, indicated model over prediction or unmeasured exposure sources. Nonetheless, our work suggested substantial amounts of dietary pesticide intake resulting from young children's handling of the food that should not be neglected and the model provided a sound base for further fine-tuning.