06-8053. Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice of availability.

SUMMARY:

EPA is announcing the availability of a final report titled, “Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043F), prepared by the National Center for Environmental Assessment (NCEA) within EPA's Office of Research and Development (ORD).

ADDRESSES:

The document is available electronically through the NCEA Web site at http://www.epa.gov/​ncea. A limited number of paper copies will be available from the EPAs National Service Center for Environmental Publications (NSCEP), P.O. Box 42419, Cincinnati, OH 45242; telephone: [phone] or 513-489-8190; facsimile: 513-489-8695. Please provide your name, your mailing address, the title and the EPA number of the requested publication.

FOR FURTHER INFORMATION CONTACT:

The Technical Information Staff, National Center for Environmental Assessment/Washington Office (8623D), U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW., Washington, DC 20460. Telephone: [phone]; fax: [phone]; e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

This final report highlights the benefits of using physiologically based pharmacokinetic (PBPK) modeling and it will be used as a learning tool for EPA scientists and health risk assessors. It describes principles of and the kind of data needed for PBPK modeling, and discusses some approaches for the evaluation and use of PBPK models in the health assessment of environmental agents. PBPK models represent an important class of dosimetry models that are useful for predicting internal doses to target organs. To predict internal dose level, PBPK models use physiological, biochemical, and physicochemical data to construct mathematical representations of processes associated with the absorption, distribution, metabolism, and elimination of compounds. With the appropriate data, these models can be used to extrapolate across species and exposure scenarios, and address various sources of uncertainty in health assessments.

This report addresses the following questions: (1) Why do risk assessors need PBPK models; (2) How can these models be used in risk assessments; and (3) What are the considerations for evaluating whether a PBPK model can be used in a given health assessment of an environmental agent?

The report is not intended to be used as Agency guidance on the use of PBPK modeling and does not specify when to use a PBPK model in health assessments of environmental agents.

Dated: September 14, 2006.

George W. Alapas,

Acting Director, National Center for Environmental Assessment.