Jump to main content or area navigation.

Contact Us

Computational Toxicology Research

Key Links
CompTox Home Basic Information Organization EPA Exposure Research Research Projects Chemical Databases Stakeholder Workshops EPA Chemical Safety Research Research Publications Scientific Reviews Communities of Practice ToxCast Data Challenges Staff Profiles CompTox Partners Jobs and Opportunities

Systems Model

Predicting chemical-induced liver toxicity requires estimates of dose-dependent adverse outcomes in humans. Currently, the risk of dose-dependent target organ toxicity in human populations is extrapolated from high-dose rodent effects using default assumptions. These extrapolations are plagued by uncertainties due to the absence of experimental data beyond the point of departure, which prevents accurate quantification of low-dose effects.  The v-Liver simulator estimates dose and time dependent effects of chemicals using in vitro data. This is a systems model of liver function that integrates physiologically based pharmacokinetic modelling (PBPK), cellular systems and molecular networks to simulate in vivo effects of chemicals.

v-Liver Simulator Components

The Virtual Liver simulates chemical-induced effects in the liver using a virtual hepatic lobule with three interconnected systems:

  • Micro-circulation/ and dosimetry: A vascular network model to quantitatively simulate the flow of nutrients and chemicals between hepatic circulation and sinusoids. To estimate microdosimetry, it uses experimental data on the clearance and plasma-protein binding of each chemical.
  • Cell and molecular response: A mechanistic model of key molecular events involved in determining the phenotypic state of cells. It uses in vitro data and the v-Liver knowledgebase to evaluate alternative mechanistic models.
  • Tissue response: An agent-based cellular systems model to represent the spatial organization and interactions between parenchymal and non-parenchymal cells.

Jump to main content.