Citation:

CHANG, D., T. L. WHITEHEAD, M. S. OKINO, C. S. MAZUR, J. F. KENNEKE, R. TORNERO-VELEZ, J. C. JOHNSON, AND C. C. DARY. AN IN SILICO INVESTIGATION OF THE ENANTIOSELECTIVE METABOLISM RATES OF TRIAZOLE FUGICIDES. Presented at 14th North American International Society for the Study of Xenobiotics Meeting, Rio Grande, PUERTO RICO, October 22 - 26, 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 in silico methods such as ab initio quantum and classical force-field methods to explore and develop an understanding for the enantioselective metabolism rates experimentally observed in the triazole fungicide bromuconazole. This directed study is pivotal for the ab initio generation of chemical-specific metabolic parameters necessary in the development of physiologically-based pharmacokinetic models used in human exposure and risk assessment studies.

Record Details: