Notice of a Scientific Peer-Review Meeting to Review the Draft Document: Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (EPA/600/R-05/043A)

AGENCY:

Environmental Protection Agency.

ACTION:

Notice of external peer-review panel meeting.

SUMMARY:

The U.S. Environmental Protection Agency (EPA) is announcing that Versar Inc., an EPA contractor for external scientific peer review, will convene a panel of experts and organize and conduct an independent external peer-review workshop to review the draft report, “Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043A), which was prepared by the National Center for Environmental Assessment (NCEA) within EPA's Office of Research and Development. Versar, Inc. invites the public to register to attend this workshop as observers. In addition, Versar, Inc. invites the public to give oral and/or provide written comments at the workshop regarding the draft document under review. The draft document and EPA's peer-review charge are available primarily via the Internet on NCEA's home page under the Recent Additions and Publications menus at http://www.epa.gov/ncea . In preparing a final report, EPA will consider Versar, Inc.'s report of the comments and recommendations from the external peer-review workshop. In addition to the workshop announced today, EPA previously published a Federal Register notice (70 FR 43692) announcing a separate process for public comment on the draft document on July 28, 2005 and a second Federal Register notice (70 FR 48950) announcing a 45-day extension (closing October 14, 2005) of the public comment period.

DATES:

Versar, Inc. will hold the peer-review workshop from November 10, 2005, to November 11, 2005. On the first day, the meeting is scheduled to begin at 8:30 a.m. and end at 5 p.m., Eastern Daylight Time. The public may attend the peer-review workshop on November 10, 2005, as observers. In addition, members of the public in attendance at the workshop will be allowed to make brief (no longer than five minutes) oral statements at the commencement of the meeting. The second day of the workshop is scheduled from 8:30 a.m. to 12:30 p.m., Eastern Daylight Time. This second day will be not be open to the public and is meant to provide time for the peer-reviewers to begin drafting their comments on the draft report.

ADDRESSES:

The external peer-review panel meeting will be held at the Hyatt Arlington located at 1325 Wilson Boulevard, Arlington, VA, 22209. The EPA contractor, Versar, Inc., is organizing, convening, and conducting the peer-review panel meeting. To attend the meeting, register by November 4, by calling Ms. Amanda Jacob of Versar, Inc., 6850 Versar Center, Springfield, VA, 22151, at 703-750-3000 ext. 260, or via e-mail at AJacob@versar.com, or by sending a facsimile to 703-642-6954. Interested parties may also register on-line at: http://epa.versar.com/pbpk . Space is limited, and reservations will be accepted on a first-come, first-served basis. At the time of your registration for the meeting, please indicate if you intend to make an oral statement during the public comment period on the first day of the meeting.

FOR FURTHER INFORMATION CONTACT:

Questions regarding registration and logistics for the peer review meeting should be directed to Ms. Amanda Jacob, Versar, Inc., 6850 Versar Center, Springfield, VA, 22151; telephone: 703-750-3000 ext. 260; facsimile: 703-642-6954; e-mail: AJacob@versar.com. If you have questions about the document, please contact Technical Information Staff, NCEA, U.S. Environmental Protection Agency, Washington, DC 20460; telephone: 202-564-3261; facsimile: 202-565-0050; or e-mail: NCEADC.Comment@epa.gov.

SUPPLEMENTARY INFORMATION:

On July 28, 2005, EPA published a Federal Register notice (70 FR 43692) that announced a 30-day public comment period through August 29, 2005, for EPA's draft report, “Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043A). EPA published a second notice in the Federal Register on August 22, 2005 (70 FR 48950) that extended the public comment period for 45 days from August 29, until October 14, 2005. On July 28, 2005, the draft document was made publicly available on NCEA's Web site for review and comment. An electronic version of the public docket is available through EPA's electronic public docket and comment system, E-Docket. To view comments, go to http://www.epa.gov/edocket/ , select “search,” then key in the docket identification number, ORD-2005-0022. In the July 28, 2005, notice, EPA also announced that a subsequent Federal Register notice would announce the date and location of a workshop for independent external peer review of this draft document. Today's notice provides information on that external peer-review workshop.

The purpose of the draft document is to describe some approaches for the use of physiologically-based pharmacokinetic (PBPK) models in risk assessment. PBPK models represent an important class of dosimetry models that are useful for predicting internal dose at target organs for risk assessment applications. Dose-response relationships that appear unclear or confusing at the administered dose level can become more understandable when expressed on the basis of internal dose of the chemical. To predict internal dose level, PBPK models use pharmacokinetic data to construct mathematical representations of biological 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 risk 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 characteristics of acceptable PBPK models for use in risk assessment?