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Exposure Related Dose Estimating Model (ERDEM)
Exposure Related Dose Estimating Model (ERDEM) A Physiologically-Based Pharmacokinetc and Pharmacodynamic (PBPK/PD) Model for Assessing Human Exposure and Risk (PDF, 160 pp., 4.8MB, About PDF), by Jerry N. Blancato, Fred W. Power, Robert N. Brown and Curtis C. Dary. EPA/600/R-06/061, June 2006.
ERDEM is a physiologically-based pharmacokinetic (PBPK) model with a graphical user interface (GUI) front end. Such a mathematical model was needed to make reliable estimates of the chemical dose to organs of animals or humans because of uncertainties of making route-to route, low-to-high exposure, and species-to-species extrapolations when there are exposures to one, or to multiple chemicals.
There is a new release of ERDEM presented here, Beta Version 5.1. It has a GUI front end, export and four model versions for small to very large models. This version contains the determination of enzyme inhibition and modeling of the transfer of chemical from a surface to skin. It has wash-off as well. There is a video tutorial, an extensive user guide and a user-friendly help system. The user can use the available comments screen to place references for parameter values. Version 5.1 has a greatly improved experimental data input screen as well as a much improved installation process. Databases from recent earlier versions of ERDEM can be converted to the version 5.1 database.
Doses may be peak concentration, area under the concentration time curve, or other measures of the chemical in given organs. Also, the metabolites of the exposure chemicals must be determined because their dose may be critical to the determination of a possible toxic event. The multitude of chemicals and their metabolites may act together, but most likely will have peak doses at different times and have different time profiles due to the nature of the exposure and the partitioning among the organs.
ERDEM solves a system of ordinary differential equations that describe the organ system consisting of lung, gastro-intestinal, dermal, liver, kidney, and other “compartments,” as needed. Metabolism, binding, and enzyme inhibition are modeled.
Experimental data is used, as available, in order to improve estimates of the various input parameters. Statistical analysis is performed as needed to determine a reasonable range of results, based on the variability and uncertainty of the input parameters. The system is flow limited, for the most part, with partition coefficients for each organ or compartment used to determine the amount of chemical species going to the compartment and that remaining in the blood.
DISCLAIMER: The model provided for download is in ERDEM5.1.exe. It has full user interface including enzyme inhibition and dermal transfer from surfaces to the skin. It includes a sample database. The parameters for a given model are in Model Data Sets. These parameters included are for test and demonstration purposes. All parameters used in the ERDEM models must be determined independently by the researcher and substantiated by references so that the model results can be evaluated based on the trustworthiness of the data sources.
Downloading ERDEM
ERDEM is a physiologically-based pharmacokinetic (PBPK) model that was developed using the Advanced Continuous Simulation Language (ACSL) from AEgis Technology Group, Inc., http://www.aegistg.com
Aegis has stopped supporting ACSL and has released acslXtreme.
The U.S. EPA sponsored the development of the ERDEM software through an Interagency Agreement with the U.S. General Services Administration which contracted to Anteon Corporation, and a GSA Schedule 70 contract, currently in place, with Anteon (now, General Dynamics Information Technology). http://www.anteon.com
Model development and usage requires ACSL and a FORTRAN package such as Compaq Visual FORTRAN. AEgis generously supplied a viewer that allows the code to be seen and the compiled models to be run (in read-only mode) without the use of ACSL or the FORTRAN program. The ERDEM 5.1 download software is provided below. A comment sheet is also provided.
Brief Instructions:
- There are two download options, save the download file to your root directory, or open it and extract the files to the root directory.
- If you wish to download ERDEM 5.1, then double click on the Download ERDEM_5.exe link. This will take up to an hour to download with high speed internet access. Extract the files to your root directory. Before installing ERDEM 5.1, you must manually delete any earlier version of ERDEM (using the software add/delete function in the Control Panel.) Then look in the ERDEM_5.1 folder and double click on the file AUTORUNPRO.EXE. This will start the installation. You must install this under your domain and have administrative privileges during this installation.
- The ERDEM 5.1 installation contains a User Guide, Video Tutorial, Release Notes, and an extensive Help system.
System Requirements:
The ERDEM 5.1 modeling system works on Windows 98, Windows NT 4.0, Windows 2000, and Windows XP. It may work on Windows ME, but has not been tested. The computer should have at least a 700 MHz processor and at least 512 MB of memory.
IMPORTANT: PLEASE REGISTER FIRST (link below) before performing the download.
We welcome comments that can be considered for future development. Comments or questions on ERDEM should be sent to erdem_model@epa.gov
ERDEM 5.1 Download:
Download ERDEM_5.exe
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