US EPA

EPA released for public comment a physiological parameters database (created using Microsoft ACCESS) intended to be used in PBPK modeling. The database contains physiological parameter values for humans from early childhood through senescence. It also contains similar data for animals (primarily rodents). This information (contained in this database) was collected through extensive search and contains physiological parameter data for humans from infancy through old age, as well as data for experimental laboratory species. To date, roughly 30% of the data entries have been verified by an independent contractor as a means of quality assurance and quality control (QA/QC). Because the QA/QC process will be ongoing during the public comment period, EPA requests that end-users focus on providing feedback regarding their experience working with the database, and not try duplicating efforts to QA the database. Users are also welcome to comment on specific studies or methods employed in the studies included in the database if desired.

The PBPK Modeling Database is available for download as a compressed Microsoft ACCESS file. To open the compressed file, first save the file on your hard drive, and unzip the contents into a folder of your choosing.

Physiologically-based pharmacokinetic (PBPK) models have increasingly been employed in chemical health risk assessments carried out by the U.S. Environmental Protection Agency (EPA), and it is anticipated that their use will continue to increase. Because relevant physiological parameter values (e.g. alveolar ventilation, blood flow and tissue volumes, glomerular filtration rate) are critical components of these models but are scattered among various sources in the scientific literature, EPA has fostered several efforts to compile these data into an electronic relational database that is intended to be suitable for use by researchers and risk assessors.

As an important class of dosimetry models, PBPK models 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.

EPA is releasing a database containing values of human and animal physiological parameters for public comment. The information assembled in this database should provide a scientific basis for selection of several key physiological parameters for dosimetry modeling for application in risk assessment.

Data entries are currently being verified by an independent contractor as a means of quality assurance and quality control (QA/QC). Comments from the public will be considered for improving the database. After the QA/QC process and the open public comment period, the database will be modified and again provided freely for download. Because the database may be updated at future intervals, modelers and others who have data that would augment the existing information or who may have other suggestions to improve the database are encouraged to email the contacts below.

Comments on the assessment may be submitted and reviewed using the e-Government Regulations.gov Web site. From the site, select Environmental Protection Agency and the keyword EPA-HQ-ORD-2009-0173 (for the docket ID) to comment on this report.