E9-8795. Physiological Parameters Database for PBPK Modeling

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice of public comment period.

SUMMARY:

EPA is announcing a public comment period for an on-line database file, using the Microsoft® Access database management system, that contains a comprehensive collection of physiological parameter data intended to be suitable for application in physiologically based pharmacokinetic (PBPK) modeling. The public comment period will be for 30 days. EPA requests that interested users comment on the functionality or usability of this resource and provide comments that may be considered for improving the final product.

The draft database represents a compilation of several individual databases developed over the past few years. It contains physiological parameter data for humans from infancy through old age, as well as data for experimental laboratory species. EPA requests that end-users provide feedback regarding their experience working with this database. Users are also encouraged to comment on specific studies or methods employed in the studies included in the entire draft database.

As a means of quality assurance and quality control (QA/QC), about 30% of the data entries, randomly selected, have been verified by an independent contractor. This QA/QC process will be ongoing.

DATES:

The 30-day public comment period begins April 16, 2009 and ends May 18, 2009. Technical comments should be in writing and must be received by EPA by close of business, May 18, 2009.

ADDRESSES:

The draft database is available for download from the U.S. EPA Web site http://cfpub.epa.gov/​ncea/​cfm/​recordisplay.cfm?​deid=​204443. Users must have Microsoft® Access in order to open and manipulate the database file.

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.

FOR FURTHER INFORMATION CONTACT:

For information on the public comment period, contact the Office of Environmental Information Docket; telephone: [phone]; facsimile: 202-566-1753; or e-mail: [e-mail].

If you have questions about the database, please contact the Information Management Staff, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC 20460; telephone: [phone]; facsimile: 703-347-8691; or e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

I. Information About the Product

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 physiological 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, lifestages, and exposure scenarios, as well as address various sources of uncertainty in risk assessments. This database contains a collection of physiological data relevant for parameterizing PBPK models for children, adults, and the elderly. In addition, the database contains physiological data for parameterizing PBPK models for young (i.e., developing) and adult rodents.

II. How To Submit Technical Comments to the Docket at Regulations.gov

Submit your comments, identified by Docket ID No. EPA-HQ-ORD-2009-0173, by one of the following methods:

• http://www.regulations.gov: Follow the on-line instructions for submitting comments.
• E-mail: [e-mail].
• Fax: [phone].
• Mail: Office of Environmental Information (OEI) Docket (Mail Code: 2822T), U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. The phone number is 202-566-1752.
• Hand Delivery: The OEI Docket is located in the EPA Headquarters Docket Center, Room 3334 EPA West Building, 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. Such deliveries are only accepted during the docket's normal hours of operation, and special arrangements should be made for deliveries of boxed information.

If you provide comments by mail or hand delivery, please submit an original 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.

Instructions: Direct your comments to Docket ID No. EPA-HQ-ORD-2009-0173. 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. It is EPA's policy to include all comments it receives in the public docket without change and to make the comments available online at http://www.regulations.gov,, including any personal information provided, unless a comment includes information claimed to be Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Do not submit information that you consider to be CBI or otherwise protected through http://www.regulations.gov or e-mail. The http://www.regulations.gov Web site is an “anonymous access” system, which means EPA will not know your identity or contact information unless you provide it in the body of your comment. If you send an e-mail comment directly to EPA without going through http://www.regulations.gov,, your e-mail address will be automatically captured and included as part of the comment that is placed in the public docket and made available on the Internet. If you submit an electronic comment, EPA recommends that you include your name and other contact information in the body of your comment and with any disk or CD-ROM you submit. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. Electronic files should avoid the use of special characters, any form of encryption, and be free of any defects or viruses. For additional information about EPA's public docket visit the EPA Docket Center homepage at http://www.epa.gov/​epahome/​dockets.htm.

Docket: Documents in the docket are listed in the http://www.regulations.gov index. Although listed in the index, some information is not publicly available, e.g., CBI or other information whose disclosure is restricted by statute. Certain other materials, such as copyrighted material, are publicly available only in hard copy. Publicly available docket materials are available either electronically in http://www.regulations.gov or in hard copy at the OEI Docket in the EPA Headquarters Docket Center.

Dated: March 16, 2009.

Rebecca Clark,

Acting Director, National Center for Environmental Assessment.