Developmental Neurotoxicity Risk Assessment of Silymarin

Question: Is there a risk of thyroid-mediated development neurotoxicity through MCT8 inhibition by silychristin when a pregnant woman takes silymarin supplements at a given dose, frequecy and duration (referring to the regulatory question 3a)?


This workflow is being implemented at this page at the moment, you can check out the webapplication here.

Steps to complete the workflow to answer the question:

  1. External Exposure Assessment: The tools that assess the magnitude, frequency, duration and exposure routes of a given exposure
    • Inputs: Magnitude, frequency, duration of silychristin exposure (numeric variables) and exposure route (categorical variable, e.g. oral)
    • No outputs for this specific question.
  2. Internal Exposure: PBPK Modeling
    • Inputs:
      1. Chemical properties: fup; Blood Plasma Ratio (BPR); Tissue-Blood partition coefficients for fat, liver, fetus, slowly perfused tissue and richly perfused tissue; CLint Liver S9; the concentration of S9 protein in the incubation; Unbound fraction in the S9 incubation; Scaling factor from S9 to liver; Unbound fraction in the liver; the absorption rate constant across the small intestine; the fraction absorbed across small intestine. These inputs are currently set in the model; however, they can be made user-defined in the final, generalized status of the workflow.
      2. Biological properties
    • Outputs:
  3. Hazard
    • Inputs:
    • Outputs:
  4. Report
    • Inputs:
    • Outputs: