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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.
Background
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
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