Skip to Content


Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment E-Docket ID No. ORD-2005-0022

Document Details

Information about this document as published in the Federal Register.

Published Document

This document has been published in the Federal Register. Use the PDF linked in the document sidebar for the official electronic format.

Start Preamble


Environmental Protection Agency.


Notice of public comment period.


The U.S. Environmental Protection Agency (EPA) is announcing a 30-day public comment period for the external review draft document titled, “Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043A). The draft document was prepared by the EPA's National Center for Environmental Assessment (NCEA) within EPA's Office of Research and Development (ORD).

EPA also anticipates that Versar, Inc., an EPA contractor for external scientific peer review, will convene a panel of experts and organize and conduct an external peer-review workshop. This workshop will be announced in a separate Federal Register notice, once EPA is notified by Versar, Inc., of the date and location for the workshop. The public comment period and the external peer-review workshop are separate processes that provide opportunities for all interested parties to comment on the document.


The 30-day public comment period begins July 28, 2005, and ends August 29, 2005. Technical comments should be in writing and must be received by EPA by August 29, 2005.


The draft document and EPA's peer-review charge are available primarily via the Internet on the National Center for Environmental Assessment's home page under the Recent Additions and Publications menus at​ncea. A limited number of paper copies are available from the Technical Information Staff, NCEA-W; telephone: 202-564-3261; facsimile: 202-565-0050. If you are requesting a paper copy, please provide your name, mailing address, and the document title, “Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043A).

Comments may be submitted electronically via EPA's E-Docket, by mail, by facsimile, or by hand delivery/courier. Please follow the detailed instructions as provided in the SUPPLEMENTARY INFORMATION section of this notice.

Start Further Info


For information on the public comment period, contact the OEI Docket; telephone: 202-566-1752; facsimile: 202-566-1753; or e-mail:

If you have questions about the document, please contact the Technical Information Staff, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC 20460; telephone: 202-564-3261; facsimile: 202-565-0050; or e-mail:

End Further Info End Preamble Start Supplemental Information


I. Information About the Document

Physiologically-based pharmacokinetic (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 external review draft document 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?

II. How To Submit Technical Comments to EPA's E-Docket

EPA has established an official public docket for information pertaining to “Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment” (EPA/600/R-05/043A), Docket ID No. ORD-2005-0022. The official public docket is the collection of materials available for public viewing and includes the documents specifically referenced in this action, any public comments received, and other information related to this action, but excludes Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. The official public docket is available for public viewing at the Office of Environmental Information (OEI) Docket in the Headquarters EPA Docket Center, (EPA/DC) EPA West Building, Room B102, 1301 Constitution Ave., NW., Washington, DC. The EPA Docket Center Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is 202-566-1744, and the telephone number for the OEI Docket is 202-566-1752; facsimile: 202-566-1753; or e-mail:

An electronic version of the public docket is available through EPA's electronic public docket and comment system, E-Docket. You may use E-Docket at​edocket/​ to submit or view public comments, to access the index of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Once in the system, select “search,” then key in the appropriate docket identification number.

Certain types of information will not be placed in E-Docket. Information claimed as CBI and other information for which disclosure is restricted by statute will not be available for public viewing in the official public docket or in E-Docket. EPA's policy is that copyrighted material will not be placed in EPA's electronic public docket but will be referenced there and will be available as printed material in the official public docket.

If you intend to submit comments to EPA, please note that it is EPA policy to make public comments available for public viewing as received at the EPA Docket Center or in E-Docket. This policy applies to information submitted electronically or in paper form, except where restricted by copyright, CBI, or statute. When EPA identifies a comment Start Printed Page 43693containing copyrighted material, EPA will provide a reference to that material in the version of the comment that is placed in EPA's electronic public docket. The entire printed comment, including the copyrighted material, will be available in the official public docket.

Public comments submitted on computer disks that are mailed or delivered to the EPA Docket Center will be transferred to E-Docket. Public comments that are mailed or delivered to the EPA Docket Center will be scanned and placed in E-Docket. Where practical, physical objects will be photographed, and the photograph will be placed in E-Docket with a brief description written by the docket staff.

You may submit comments electronically, by mail, by facsimile, or by hand delivery/courier. To ensure proper receipt by EPA, include the appropriate docket identification number with your submission. Please ensure that your comments are submitted within the specified comment period. Comments received after the closing date will be marked “late,” and may only be considered if time permits.

If you submit comments electronically, EPA recommends that you include your name, mailing address, and an e-mail address or other contact information in the body of your comment. Also include this contact information on the outside of any submitted disk or CD-ROM, and in any cover letter accompanying the disk or CD-ROM. This ensures that you can be identified as the person submitting the comment and allows EPA to contact you in case the Agency cannot read your submission due to technical difficulties or needs further information on the substance of your comment. EPA will not edit your comment, and any identifying or contact information provided in the body of a comment will be included as part of the comment that is placed in the official public docket and made available in E-Docket. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, it may delay or preclude consideration of your comment.

Electronic submission of comments to E-Docket is EPA's preferred method for receiving comments. Go directly to EPA Dockets at​edocket, and follow the online instructions for submitting comments. To access EPA's electronic public docket from the EPA Internet Home Page, select “Information Sources,” “Dockets,” and “EPA Dockets.” Once in the system, select “search,” and then key in Docket ID No. ORD-2005-0022. The system is an “anonymous access” system, which means EPA will not know your identity, e-mail address, or other contact information unless you provide it in the body of your comment.

Comments may be sent by electronic mail (e-mail) to, Attention Docket ID No. ORD-2005-0022. In contrast to EPA's electronic public docket, EPA's e-mail system is not an “anonymous access” system. If you send an e-mail comment directly to the docket without going through EPA's E-Docket, EPA's e-mail system automatically captures your e-mail address, and it becomes part of the information in the official public docket and in E-Docket.

You may submit comments on a disk or CD-ROM that you mail to the OEI Docket mailing address. Files will be accepted in WordPerfect, Word, or PDF format. Avoid the use of special characters and any form of encryption.

If you provide comments in writing, please submit one unbound original with pages numbered consecutively, and three copies of the comments. For attachments, provide an index, number pages consecutively with the comments, and submit an unbound original and three copies.

Start Signature

Dated: July 22, 2005.

Peter W. Preuss,

Director, National Center for Environmental Assessment.

End Signature End Supplemental Information

[FR Doc. 05-14932 Filed 7-27-05; 8:45 am]