Harmonized TCE PBPK Model


Please check this website for process updates, including opportunities to participate.  If you would like further information or would like to be added to an email contact list for project updates, please contact Dr. Lynne Haber at (513) 542-7475 x17 or through email: haber@tera.org.

Project Description

Development of a Harmonized PBPK Model for TCE and Its Metabolites

At the request of the United States Air Force (USAF) and the United States Environmental Protection Agency (EPA), Toxicology Excellence for Risk Assessment (TERA) facilitated and provided support to a USAF-EPA workgroup developing a harmonized physiologically-based pharmacokinetic (PBPK) model for trichloroethylene (TCE) and its metabolites.  The intent of this project is to use the best science and updated data to derive a comprehensive TCE PBPK model as an input for ongoing TCE risk assessment activities.   To complete this effort, TERA provided technical support to the USAF-EPA workgroup, that included input from scientists from academia and private consulting who are experienced in developing TCE PBPK models, toxicokinetics of TCE and its metabolites, biostatistics, and TCE risk assessment.  The resulting model was subject to a peer consultation organized by TERA in June 2004, which was open to the public.


Physiologically-based pharmacokinetic (PBPK) modeling is a useful method for improving the accuracy of chemical risk assessment.  Since TCE metabolism varies in different tissues and organs, and the active chemical species responsible for the adverse effects in various organs are different, sophisticated PBPK models are required in order to describe the kinetics of these chemical species in biological systems.  The toxicokinetics of TCE and its metabolites in the body have been studied extensively in many animal species, and in humans.  Based on these data, several PBPK models have been developed and published.  Two research groups have independently developed TCE PBPK models (Fisher 2000, Clewell et al, 2000) that have been used in TCE risk assessment.  Because of the difference in the toxicokinetic data used, difference in the model structure, and overall model complexity, it becomes a challenge for one to compare and evaluate these models.  Furthermore, neither of these models has been updated to include newly available kinetic data for TCE and its metabolites.

This project is designed to utilize all the toxicokinetic data available to derive a comprehensive TCE PBPK model as an input for ongoing TCE risk assessment activities.   The USAF-EPA Working Group, with technical expertise from TERA and scientists such as Dr. Fisher and Mr. Clewell under contract to the U.S. Air Force, is reviewing the available models and recent data, and is working to develop a harmonized model.   In addition, a peer consultation process will serve to provide broader scientific input to the project. Independent peer consulters will include other PBPK and TCE metabolism experts who have not been directly involved in the development of the harmonized TCE PBPK model.  Based on the recommendations from the peer consultation, the updated model will be revised, calibrated, and uncertainties will be evaluated. 

PBPK Peer Consultation Meeting

A peer consultation meeting on a draft harmonized physiologically-based pharmacokinetic (PBPK) model for trichloroethylene (TCE) was held on Tuesday, June 29, 2004 at the Kingsgate Conference Center of the University of Cincinnati .  An independent panel of expert scientists met in a public meeting to provide comments on the draft model.  This effort was undertaken at the request of the United States Air Force (USAF) and the United States Environmental Protection Agency (EPA).  The panel members provided input and recommendations to the authors in a number of areas.  A brief summary of the meeting results is available below and a more detailed meeting report will be made public in late summer.

What:    PBPK Model Peer Consultation Meeting
When:   June 29, 2004
Where:  Marriott Kingsgate Conference Center at University of Cincinnati , Cincinnati , Ohio

Harmonized TCE PBPK Model and Documentation