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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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