Use of Physiologically Based Pharmacokinetic Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk (Final Report)

Background

This final report, Use of Physiologically Based Pharmacokinetic Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement (PDF, 234 pp, 1MB), addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. It is the result of Cooperative Agreement CR828047010 between US EPA/ORD/NCEA and the Chemical Industry Institute for Toxicology(CIIT) and Dr Gregory Kedderis. It comprises five chapters; topics and results covered in the first four chapters have been published in the peer reviewed scientific literature.

Topics covered include:

- Data Quality Objectives
- Experimental Framework
- Required Data
- Two example case studies that develop and incorporate in vitro metabolic rate constants in PBPK models designed to quantify human interindividual variability to better direct the choice of uncertainty factors for health risk assessment.

History/Chronology

The following is a brief history of the development of the report:

2002/03: Chapters 1-4 results were published in peer reviewed literature.
Jul 2004: A draft of Chapter 5 was released for internal review.
Oct 2004: A draft of Chapter 5 released for external review.
Dec 2004: Simplified acquisition developed to refine the final case study (Chapter 5).
Jun 2005: A draft of the full document was subjected to peer consultation.
Apr 2006: EPA released the final report.

Next Steps

This is the final document. Results from Chapter 5 (the final case study) will be published in the peer reviewed literature.

Citation:

Use of Physiologically Based Pharmacokinetic Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk (Final Report). U.S. Environmental Protection Agency, Washington, D.C., EPA/600/R-06/014A.

Contact Information:

John C. Lipscomb
- by phone at: 5135697217
- by fax at:
- or by email at: lipscomb.john@epa.gov