Statistical analysis of Clewell et al PBPK model of trichloroethylene kinetics

Abstract : A physiologically based pharmacokinetic model for trichloroethylene (TCE) in rodents and humans was calibrated with published toxicokinetic data sets. A Bayesian statistical framework was used to combine previous information about the model parameters with the data likelihood, to yield posterior parameter distributions. The use of the hierarchical statistical model yielded estimates of both variability between experimental groups and uncertainty in TCE toxicokinetics. After adjustment of the model by Markov chain Monte Carlo sampling, estimates of variability for the animal or human metabolic parameters ranged from a factor of 1.5-2 (geometric standard deviation [GSD]). Uncertainty was of the same order as variability for animals and higher than variability for humans. The model was used to make posterior predictions for several measures of cancer risk. These predictions were affected by both uncertainties and variability and exhibited GSDs ranging from 2 to 6 in mice and rats and from 2 to 10 for humans
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://hal-ineris.archives-ouvertes.fr/ineris-00961854
Contributor : Gestionnaire Civs <>
Submitted on : Thursday, March 20, 2014 - 3:26:25 PM
Last modification on : Wednesday, November 29, 2017 - 3:16:04 PM
Long-term archiving on : Friday, June 20, 2014 - 12:05:11 PM

File

2001-027.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : ineris-00961854, version 1
  • INERIS : PU-2001-027
  • PUBMED : 10807560

Collections

Citation

Frédéric Y. Bois. Statistical analysis of Clewell et al PBPK model of trichloroethylene kinetics. Environmental Health Perspectives, National Institute of Environmental Health Sciences, 2000, 108 (suppl. 2), pp.307-316. ⟨ineris-00961854⟩

Share

Metrics

Record views

159

Files downloads

448