Bayesian evaluation of a physiologically-based pharmacokinetic (PBPK) model of long-term kinetics of metal nanoparticles in rats

Details

• Personal Author:
  Haber LT ; Kuempel, Eileen D. ; MacCalman L ; Sweeney LM ; Tran CL
• Description:
  Biomathematical modeling quantitatively describes the disposition of metal nanoparticles in lungs and other organs of rats. In a preliminary model, adjustable parameters were calibrated to each of three data sets using a deterministic approach, with optimal values varying among the different data sets. In the current effort, Bayesian population analysis using Markov Chain Monte Carlo (MCMC) simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. The previously-developed model structure and some physiological parameter values were modified to improve physiological realism. The data from one of the three previously-identified studies and from two other studies were used for model calibration. The data from the one study that adequately characterized mass balance were used to generate parameter distributions. When data from a second study of the same nanomaterial (iridium) were added, the level of agreement was still acceptable. Addition of another data set (for silver nanoparticles) led to substantially lower precision in parameter estimates and large discrepancies between the model predictions and experimental data for silver nanoparticles. Additional toxicokinetic data are needed to further evaluate the model structure and performance and to reduce uncertainty in the kinetic processes governing in vivo disposition of metal nanoparticles. [Description provided by NIOSH]
• Subjects:
  Metals Occupational Health Safety Toxicology
• Keywords:
  Analytical-instruments Analytical-models Author Keywords: Nanoparticles Bayesian Analysis Biokinetics Biostatistics Kinetics Markov Chain Monte Carlo Mathematical-models Metal-compounds Nanotechnology Pharmacodynamics Physiological-function Physiologically-based Pharmacokinetic Model Quantitative-analysis Simulation-methods Statistical-analysis

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• ISSN:
  0273-2300
• Document Type:
  Text
• Funding:
  Contract ; Interagency Agreement
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  EID - Education and Information Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  151-163
• Volume:
  73
• Issue:
  1
• NIOSHTIC Number:
  nn:20046499
• Citation:
  Regul Toxicol Pharmacol 2015 Oct; 73(1):151-163
• Contact Point Address:
  Lisa M. Sweeney, Henry M. Jackson Foundation for the Advancement of Military Medicine, Naval Medical Research Unit Dayton, 2729 R St., Building 837, Wright-Patterson Air Force Base, OH 45433, USA
• Email:
  LMS29@cwru.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Regulatory Toxicology and Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d8237feaf9441cae34f6cc08fffcae94f7e4c373bc8807d698f478a22191e60693b0473896130cf98e465a3981b43ade37b4dac4b28cdaaf4a52d0ac02da497b
• Download URL:
  https://stacks.cdc.gov/view/cdc/201545/cdc_201545_DS1.pdf
• File Type:
  [PDF - 1.62 MB ]