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INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS
Citation:
CHANG, D., P. P. EGEGHY, J. B. KNAAK, R. TORNERO-VELEZ, M. S. OKINO, F. W. POWER, M. DELLARCO, C. S. MAZUR, J. F. KENNEKE, AND C. C. DARY. INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS. Presented at ISEA/ISEE 2006 , Paris, FRANCE, September 02 - 06, 2006.
Impact/Purpose:
The overall goal of this work is to reduce the uncertainty in risk assessment. The chemical-specific models developed under this task highlight common methods, analyses, and data requirements for general dose modeling. Specific objectives relate directly to customer needs and contributions to the scientific field.
1)Quantify the relevant dose metrics, and associated uncertainties, under scenarios of regulatory interest.
2)Develop and evaluate methods for species-to-species, age, and route-to-route extrapolation.
3)Evaluate and identify important mechanisms of chemical interaction for cumulative risk assessment.
4)Identify data gaps, and recommend targeted experimental studies to reduce the uncertainties in the dose metric estimates.
5)Provide information on common ADME pathways to recommend enhancements of the general ERDEM dose modeling platform.
6)Develop specific chemical and chemical class PBPK/PD models to support pesticide product registration and re-registration demands through 2008 (EPA Strategic Plan Objective 4.1.1: Reduce exposure to toxic pesticides).
Description:
The objective of this work is to use the Exposure Related Dose Estimating Model (ERDEM) and quantitative structure-activity relationship (QSAR) models to develop an assessment tool for human exposure assessment to triazole fungicides. A dermal exposure route is used for the physiological based pharmacokinetic model and matrix formulation effects are simulated for propiconazole.