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The purpose of this portal is to create a collection of AOPs on the molecular level for the AOPs that are, or will be created for the EU-ToxRisk program, in which Open PHACTS Foundation (OPF) is responsible for AOP creation. The subjects of the first AOPs are linked to the use cases of the EU-ToxRisk program, and there will be a team of experts involved in the creation of each AOP.

The proposed list of the first set of AOPs to be created, some are more defined than others:

  • Decrease of lysosomal phospholipase activity leads to phospholipidosis
  • Immune-mediated liver injury
  • Reduced mitochondrial activity leads to cholestasis
  • Liver fibrosis
  • Unfolded protein response-mediated liver toxicity
  • Increased ROS levels lead to hepatotoxicity
  • Inhibition of mitochondrial complex I of nigra-striatal neurons leads to parkinsonian motor deficits
  • Decreased ATP production leads to neurodegeneration
  • Peripheral neuropathy caused by microtubule interacting drugs
  • Oxidative reactivity leads to chemical-induced fanconi syndrome
  • Oxidative reactivity leads to acceleration of chronic kidney disease
  • Compound accumulation via Megalin/Cubilin uptake leads to acute and chronic kidney disease
  • Renal proximal tubular uptake via organic cation transporters leads to...
  • Oxidative stress leads to COPD
  • Activation of Smad signaling leads to pulmonary fibrosis
  • Impaired HDAC leads to limbosacral spina bifida
  • HDAC inhibition leads to neural tube defects
  • Cyt p450 inhibition leads to Feminization and Masculinization
  • Estrogen/androgen ...
  • Bone malformation
  • Oxidative stress-induced hepatoxicity
  • Inflammatory cytokine-induced cell death
  • HDAC inhibition leads to impaired craniofacial development

Basic strategies and principles for general AOPs are described in this paper:

Villeneuve et al. (2014). Adverse Outcome Pathway (AOP) Development I: Strategies and Principles. Toxicological Sciences PubMed

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