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Human Exposure and Atmospheric Sciences

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Exposure Related Dose Estimating Model (ERDEM)

EPA’s Exposure Related Dose Estimating Model (ERDEM) is a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PD) modeling system, developed by EPA scientists to predict how chemicals move through and concentrate in human tissues and body fluids. With ERDEM, scientists are able to examine how chemical exposures impact organs and tissues in the human body and determine how long they will take to be naturally processed or expressed.

The ERDEM framework provides the flexibility for scientists to use either existing models or build new PBPK and PBPK/PD models to address specific science questions. ERDEM has been applied to a variety of chemicals as part of EPA’s regulatory risk assessment process, including malathion and N- methyl carbamate.

System Requirements
The ERDEM 5.1 modeling system works on Windows 98, Windows NT 4.0, Windows 2000, and Windows XP. The computer should have at least a 700 MHz processor and 512 MB of memory.

ERDEM was developed using Advanced Continuous Simulation Language (ACSL) from AEgis Technology Group, Inc. Aegis no longer supports ACSL and has released acslXtreme.

Model development and usage requires ACSL and a FORTRAN package such as Compaq Visual FORTRAN, however, the AEgis Technology Group, has 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.

Components of ERDEM
The ERDEM system includes three components:

  • The ERDEM Front End – a Windows-based application that allows users to enter exposure, pharmacokinetic, and pharmacodynamic parameters and data to store them in a database for later use, and then export them to a command file for input to the ERDEM Modeling Engine
  • The ERDEM Modeling Engine – which contains differential equations that use the physiological, biological, and pharmacodynamic modeling data that are entered via the ERDEM Front End. The various features of the modeling engine (compartments, metabolism, exposure, and enzyme inhibition) are accessed by flags set by the user. The engine uses Advanced Continuous Simulations Language (ACSL) to build the ERDEM models.
  • The ACSL Viewer – is part of the ACSLTOX modeling engine environment that allows users to start and view model run results.

Support Materials
The following document provides references and details on how to use the ERDEM system: Exposure Related Dose Estimating Model (ERDEM) A Physiologically-Based Pharmacokinetc and Pharmacodynamic (PBPK/PD) Model for Assessing Human Exposure and Risk

External Peer Reviews

Download Tips for ERDEM 5.1
The ERDEM 5.1 installation contains a User Guide, Video Tutorial, Release Notes, and an extensive Help system. There are two options for downloading ERDEM 5.1:

  • 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 the download ERDEM_5.exe link in the box to the right. It will take up to an hour to download with high-speed Internet.

If you wish to extract the files to your root directory, you must manually delete earlier versions of ERDEM (using the add/delete function in your computer’s Control Panel), before installing ERDEM 5.1. Once you have deleted earlier versions of ERDEM, you can 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.

ERDEM 5.1 includes a sample database. The parameters for a given model are in Model Data Sets. The parameters included are for test and demonstration purposes only. All parameters used in the ERDEM models must be determined independently by the researcher and substantiated by references so that model results can be evaluated based on trustworthy data sources.

Publications

  • Abbas, R., Fisher, J.W. 1997. “A Physiologically-Based Pharmacokinetic Model for Trichloroethylene and Its Metabolites, Chloral Hydrate, Trichloroacetate, Dichloroacetate, Trichloroethanol, and Trichloroethanol Glucuronide in B6C3F1 Mice.” Toxicol Appl Pharmacol 147: 15-30.
  • Blancato, J.N, Power, F.W., Wilkes, C.R., Tsang, A.M., Hern, S.C. and Olin, S.S. 2002. “Integrated probabilistic and deterministic modeling techniques in estimating exposure to water-borne contaminants: Part2: Pharmacokinetic Modeling” Proceedings: Indoor Air 2002, 9th International Conference on Indoor Air Quality and Climate. 262-267.
  • Clewell H.J., Gentry P.R., Allen B.C., Covington T.R., et al. 2000. “Development of a Physiologically based Pharmacokinetic Model of Trichloroethylene and its Metabolites for Use in Risk Assessment.” Environmental Health Perspectives. 108 (Supplement 2): 283-305.
  • Corley, RA, Mendrala, A.L., Smith, F.A., Staats, D.A., Gargas, M.L., Conolly, R.B., Andersen, M.E., and Reitz, R.H. 1990 “Development of a Physiologically Based Pharmacokinetic Model for Chloroform.” Toxicol Appl Pharmacol. 103: 512-527.
  • Dary, C.C., Blancato, J.N., Castles, M., Reddy, V., Cannon, M., Saleh, M.A., and Cash, G.G. "Dermal Absorption and Disposition of Formulations of Malathion in Sprague-Dawley Rats and Humans" in Biomarkers of Human Exposure, ACS Symposium Series No. 542, Saleh, M., C. Nauman, and J. Blancato, eds. American Chemical Society 1993.
  • Fisher, J.W., Mahle, D., and Abbas,R. 1998. “A Human Physiologically Based Pharmacokinetic Model for Trichloroethylene and Its Metabolites, Trichloroacetic Acid and Free Trichloroethanol.” Toxicol. Appl. Pharmacol. 152: 339-359.
  • Gargas, M.L., Burgess, R.J., Voisard, D.E., Cason, G.H., and Andersen, M.E. 1989. “Partition Coefficients of Low-Molecular Weight Volatile Chemicals in Various Liquids and Tissues.” Toxicol. Appl. Pharmacol. 98, 87-99.
  • Nihlén, A., Johanson, G. 1999 Physiologically based Toxicokinetic modeling of inhaled methyl tertiary-butyl ether in humans. Toxicol Sci 51:184-194.
  • Staats, D.A., Fisher, J.W., and Connolly, R.B. 1990 Gastrointestinal Absorption of Xenobiotics in Physiologically Based Pharmacokinetic Models, a Two-Compartment Description. The American Society for Pharmacology and Experimental Therapeutics. 19, No. 1: 144-148.
  • U.S. EPA. August 1997b. Exposure Factors Handbook, Volume III, Activity Factors. EPA/600/P-95/002Fc. U.S. EPA, Office of Research and Development, National Center for Environmental Assessment.
  • U.S. EPA. 1997. “Guiding Principals for Monte Carlo Analysis.” EPA/630/R-97/001. Available at http://www.epa.gov/raf/publications/guiding-monte-carlo-analysis.htm.

Questions/Comments
Contact: erdem_model@epa.gov

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