Citation:

MIRFAZAELIAN, A., K. KIM, S. S. ANAND, H. J. KIM, R. TORNERO-VELEZ, J. V. BUCKNER, AND J. W. FISHER. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN ADULT AND DEVELOPING SPRAGUE-DAWLEY RATS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 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:

This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights of rats of different ages. The PBPK model predictions compared favorably with experimental blood, brain and fat DLT profiles over the range of doses. The model will aid in our understanding of the processes affecting the disposition of pyrethroids in humans.

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