PLETHEM

PLETHEM

PLETHEM stands for Population Lifecourse Exposure-To-Health-Effects Model Suite. This computational platform is being developed by ScitoVation under a Memorandum of Understanding with EPA's National Exposure Research Laboratory and National Center for Computational Toxicology.

PLETHEM will provide a freely available, open-source, user-friendly platform for rapid modeling across the source-to-outcome continuum.

Value Proposition

PLETHEM's modular design approach supports a variety of exposure and PBPK models in order to provide a wide range of capabilities:

  • Provide quantitative dosimetry to bridge between exposures and potential health outcomes
  • Population level simulations
  • Lifetime exposure modeling capability
  • Test alternative exposure estimates against human biomonitoring data (Reverse Dosimetry)
  • Support rapid quantitative risk assessments from in vitro studies (HT-IVIVE)
  • Replace studies in neonatal animals with in vitro human metabolism and PBPK (Early-Life Sensitivity Modeling)
  • Provide a user-friendly run-time platform for PBPK models

Capabilities

PLETHEM includes both generic PBPK models and chemical-specific (bespoke) PBPK modeling capabilities. Currently available generic models include:

  • CEFIC's IndusChemFate PBPK model, which supports rapid estimation of tissue dose for new chemicals
    • Single or multiple exposure routes (oral, dermal and inhalation)
    • 11 physiological compartments, including metabolites
    • Database of chemicals and physiological parameters
    • Partition Coefficients estimated using QSAR models
    • Accepts a variety of in vitro metabolism data
  • NCCT httk Model
    • Rapid, conservative PBPK modeling for chemicals with limited data
  • HT-IVIVE Model
    • Supports rapid in vitro to in vivo extrapolation of high-throughput toxicity testing results
    • Implements approach developed by The Hamner Institutes for ToxCast

Continuing Development

Additional PBPK models are currently being added to PLETHEM to support early life sensitivity modeling, and PLETHEM. Work is also underway to provide a user-friendly interface for user-definition of a new PBPK model within PLETHEM.

PLETHEM is being designed to accept inputs from multiple EPA and OECD exposure estimation programs, including CEM, TRA, SEEM2, and SHEDS-HT. This exposure information can then be used to drive PBPK model-based estimates of resulting internal tissue exposures to support risk assessments. In the future, PLETHEM will also be able to link these internal exposures to cellular pathway models to provide quantitative Adverse Outcome Pathway dose-response modeling.

*PLETHEM has been developed with the support of the American Chemistry Council.