PMID- 17299829
OWN - NLM
STAT- MEDLINE
DCOM- 20071009
LR  - 20070409
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 27
IP  - 3
DP  - 2007 May-Jun
TI  - Evaluation of physiologically based pharmacokinetic models for use in risk 
      assessment.
PG  - 218-37
AB  - Physiologically based pharmacokinetic (PBPK) models are sophisticated dosimetry 
      models that offer great flexibility in modeling exposure scenarios for which 
      there are limited data. This is particularly of relevance to assessing human 
      exposure to environmental toxicants, which often requires a number of 
      extrapolations across species, route, or dose levels. The continued development 
      of PBPK models ensures that regulatory agencies will increasingly experience the 
      need to evaluate available models for their application in risk assessment. To 
      date, there are few published criteria or well-defined standards for evaluating 
      these models. Herein, important considerations for evaluating such models are 
      described. The evaluation of PBPK models intended for risk assessment 
      applications should include a consideration of: model purpose, model structure, 
      mathematical representation, parameter estimation, computer implementation, 
      predictive capacity and statistical analyses. Model purpose and structure require 
      qualitative checks on the biological plausibility of a model. Mathematical 
      representation, parameter estimation, computer implementation involve an 
      assessment of the coding of the model, as well as the selection and justification 
      of the physical, physicochemical and biochemical parameters chosen to represent a 
      biological organism. Finally, the predictive capacity and sensitivity, 
      variability and uncertainty of the model are analysed so that the applicability 
      of a model for risk assessment can be determined. Published in 2007 by John Wiley 
      & Sons, Ltd.
FAU - Chiu, Weihsueh A
AU  - Chiu WA
AD  - National Center for Environmental Assessment, Office of Research and Development, 
      U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington, 
      DC 20460, USA.
FAU - Barton, Hugh A
AU  - Barton HA
FAU - DeWoskin, Robert S
AU  - DeWoskin RS
FAU - Schlosser, Paul
AU  - Schlosser P
FAU - Thompson, Chad M
AU  - Thompson CM
FAU - Sonawane, Babasaheb
AU  - Sonawane B
FAU - Lipscomb, John C
AU  - Lipscomb JC
FAU - Krishnan, Kannan
AU  - Krishnan K
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Hazardous Substances)
SB  - IM
MH  - Algorithms
MH  - Animals
MH  - Computer Simulation
MH  - Hazardous Substances/*pharmacokinetics
MH  - Humans
MH  - *Models, Biological
MH  - Monitoring, Physiologic/methods
MH  - Reproducibility of Results
MH  - Risk Assessment/methods
RF  - 144
EDAT- 2007/02/15 09:00
MHDA- 2007/10/10 09:00
CRDT- 2007/02/15 09:00
PHST- 2007/02/15 09:00 [pubmed]
PHST- 2007/10/10 09:00 [medline]
PHST- 2007/02/15 09:00 [entrez]
AID - 10.1002/jat.1225 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2007 May-Jun;27(3):218-37. doi: 10.1002/jat.1225.