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

EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. This report describes and demonstrates techniques necessary to extrapolate and incorporate in vitro derived metabolic rate constants in PBPK models. It also includes two case study examples designed to demonstrate the applicability of such data for health risk assessment and addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. 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.

    This report is the result of Cooperative Agreement CR828047010 between US EPA/ORD/NCEA and the Chemical Industry Institute for Toxicology(CIIT) and Dr Gregory Kedderis.

Status

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

Citation

U.S. EPA. Use of Physiologically Based Pharmacokinetic (PBPK) 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.

History/Chronology

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