Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (External Review Draft 2005)

Abstract

This draft report of Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment addresses the application and evaluation of PBPK models for risk assessment purposes. These models represent an important class of dosimetry models that are useful for predicting internal dose at target organs for risk assessment applications.

Topics covered include:

• the types of data required use of PBPK models in risk assessment,
• evaluation of PBPK models for use in risk assessment, and
• the application of these models to address uncertainties resulting from extrapolations (e.g. interspecies extrapolation) often used in risk assessment.

In addition, appendices are provided that include

• a compilation of chemical partition coefficients and rate constants,
• algorithms for estimating chemical-specific parameters, and
• a list of publications relating to PBPK modeling.

Impact/Purpose

This report is primarily meant to serve as a learning tool for EPA scientists and risk assessors who may be less familiar with the field. In addition, this report can be informative to PBPK modelers within and outside the Agency, as it provides an assessment of the types of data and models that the EPA requires for consideration of a model for use in risk assessment.

Status

In summer 2005, there will be a meeting in Washington, DC for the purpose of providing an independent scientific peer review of this document. EPA will issue a separate notice, to be published in the Federal Register, that will give the dates and place of this public meeting. The notice will describe procedures for the public to register, without cost, to attend the meeting and to give written and/or oral comment before the peer review panel. With the completion of the scientific peer review, EPA will review all comments received, including public comments, to finalize the document.

Once this is done, the final report, which addresses both public and peer review comments, will be published and available from the EPA Web site.

Citation

U.S. EPA. Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (External Review Draft 2005). U.S. Environmental Protection Agency, Washington, D.C., EPA/600/R-05/043A, 2005.

Date	Description
01- 2003	EPA award released a solicitation for a contract to develop a report for the "Application of Physiologically Based Pharmacokinetic Data and Models in Risk Assessment."
02- 2004	A draft document was released for internal review.
03- Jul 2005	EPA released the external review draft for public comment and peer review
04- Nov 2005	A draft of this report was subjected to an external review by a panel of independent experts.

This download(s) is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency determination or policy.

• Approaches For The Application Of Physiologically Based Pharmacokinetic (Pbpk) Models And Supporting Data In Risk Assessment - 2005 External Peer Review (PDF)  (110  pp, 997.1 KB, about PDF)
• Appendix 1: Algorithims for Predicting Chemical-Specific Parameters for PBPK Models (PDF)  (17  pp, 272.5 KB, about PDF)
• Appendix 2: List of Publications Relevant to PBPK Modeling of Environmental Chemicals and it's Use (PDF)  (90  pp, 381.8 KB, about PDF)
• Appendix 3: Partition Coefficients and Metabolic Rate Constants for PBPK Modeling of Environmental Chemicals (PDF)  (147  pp, 2.5 MB, about PDF)
• Summary Report of the Panel Peer Review Discussion of the PBPK Document (PDF)  (19  pp, 115.2 KB, about PDF)
• Disposition of Comments from the PBPK Peer-Review (PDF)  (11  pp, 60.5 KB, about PDF)

Related Link(s)

• Approaches For the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data In Risk Assessment (Final Report)