A Simple Toxicokinetic Model Exhibiting Complex Dynamics and Nonlinear Exposure Response

Details

• Personal Author:
  Park RM
• Description:
  Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects. [Description provided by NIOSH]
• Subjects:
  Occupational Exposure Occupational Health Risk Assessment Safety
• Keywords:
  Analytical Models Author Keywords: Dose Response Biological Systems Chronic Exposure Dose Response Gene Regulation Homeostasis Hormesis Kinetics Metabolic Equilibrium PBPK Risk Analysis Risk Assessment Simulation Simulation Methods Upregulation

  More +
• ISSN:
  0272-4332
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSI - Division of Science Integration
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  40
• Issue:
  12
• NIOSHTIC Number:
  nn:20060323
• Citation:
  Risk Anal 2020 Dec; 40(12):2561-2571
• Contact Point Address:
  Robert Park, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Division of Science Integration, Risk Eval uation Branch, 1090 Tusculum Ave, MS C-15, Cincinnati OH 45226-1998, USA
• Email:
  rhp9@cdc.gov
• Federal Fiscal Year:
  2021
• Peer Reviewed:
  True
• Source Full Name:
  Risk Analysis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6fa18234cc9e1266525acd436a78c1cd4e2dadee76150a937b28a9fd43aec0daf8711180635b57d88c750ded78753a01442c965274857910b8ae5ba201fcec5e
• Download URL:
  https://stacks.cdc.gov/view/cdc/224265/cdc_224265_DS1.pdf
• File Type:
  [PDF - 888.75 KB ]