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Table 4 Available in vitro systems for portal of entry testing

From: Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

Portal of Entry Cell/Tissue Type Effect Endpoint Research Gap
Lung Epithelium Toxicity Trypan blue, LDH, apoptosis  
   Inflammation Gene expression, oxidative stress, signal transduction pathways  
   Translocation Transfer of nanoparticles across membranes Translocation process
   Carcinogenesis Genotoxicity, comet assay, 8OHdG, hprt assay, proliferation assay  
  Macrophages Toxicity Trypan blue, LDH, apoptosis  
   Chemotaxis Chemotaxis assay Recognition/Activation/Phagocytosis Process
   Phagocytosis Particle uptake into cells, cytoskeletal staining  
   Inflammation Gene expression, oxidative stress, signal transduction pathways Additional markers?
  Immune Cells Immune response Cytokine profile, adjuvant effects Additional markers?
  Endothelium Inflammation Adhesion molecules, oxidative stress Additional markers?
   Coagulation Von Willebrand factor, tissue factor  
  Fibroblasts Inflammation Oxidative stress, cytokine profile, gene expression profile  
   Fibrosis Collagen synthesis, cell proliferation  
  Lung slices Inflammation Oxidative stress, signal transduction pathway, immuno-histopathology  
   Translocation Particles across membranes Translocation process
   Fibrosis Collagen synthesis  
Skin Cell systems (e.g. HEK) Cytotoxicity Inflammation Cell viability – MTT, neutral red, Cytokine profile  
  Flow-through diffusion systems Absorption   
  Isolated Skin Flap Model Absorption, Cytotoxicity, Inflammation Glucose utilization, any other markers depending on end points (cytokine profiles, histopath, etc.)  
Mucosa Intestinal epithelium (GI tract) Cytotoxicity Cell viability – MTT, neutral red, trypan blue Apoptosis  
   Inflammation Cytokine profile, oxidative stress, signal transduction pathway  
   Translocation Permeability assays  
  GALT Inflammation Cytokine profile, oxidative stress  
   Immune response Adjuvant effects Additional markers?
  Buccal epithelium (oral cavitiy) Cytotoxicity Cell viability – MTT, neutral red, trypan blue Apoptosis  
   Inflammation Cytokine profile, oxidative stress, signal transduction pathway  
   Translocation Permeability assays  
  Vaginal epithelium (reproductive system) Cytotoxicity Cell viability – MTT, neutral red, trypan blue Apoptosis  
   Inflammation Cytokine profile, oxidative stress, signal transduction pathway  
   Translocation Permeability assays  
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