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Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
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Related Experiment Video

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Putative adverse outcome pathways relevant to neurotoxicity.

Anna Bal-Price1, Kevin M Crofton, Magdalini Sachana

  • 1European Commission Joint Research Centre, Institute for Health and Consumer Protection , Ispra , Italy.

Critical Reviews in Toxicology
|January 22, 2015
PubMed
Summary

The Adverse Outcome Pathway (AOP) framework aids understanding of toxicity pathways. A workshop identified potential AOPs for neurotoxic outcomes, forming a basis for future risk assessment.

Keywords:
adverse outcome pathwayin vitro testingkey eventsmolecular initiating eventpathways of neurotoxicitypredictive toxicology

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Area of Science:

  • Toxicology
  • Neuroscience
  • Risk Assessment

Background:

  • The Adverse Outcome Pathway (AOP) framework aids understanding of toxicity mechanisms.
  • It links molecular initiating events (MIEs) through key events (KEs) to adverse outcomes (AOs).
  • Few documented AOPs exist for neurotoxic and developmental neurotoxic outcomes in the central and peripheral nervous systems.

Purpose of the Study:

  • To identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes.
  • To lay the groundwork for developing detailed AOPs for neurotoxicity.
  • To support human health risk assessment using a mechanism-based approach.

Main Methods:

  • A workshop organized by EURL ECVAM in March 2013.
  • Identification of potential AOPs for neurotoxic and developmental neurotoxic outcomes.
  • Discussion of causally linked MIEs and KEs leading to AOs in the CNS and PNS.

Main Results:

  • Potential AOPs relevant to neurotoxicity were identified.
  • The outlined AOPs are not fully described but serve as a foundation.
  • The workshop provided a basis for further AOP development and evaluation.

Conclusions:

  • The AOP framework is valuable for understanding toxicity pathways.
  • Further development of AOPs is needed for neurotoxic outcomes.
  • These AOPs can enhance human health risk assessment by focusing on mechanisms.