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Session 28

Quantification: a key aspect in transitioning mechanistic approaches from hazard identification to risk assessment

Programme of the Session

  • Challenges and considerations in quantifying mechanistic data 
    Jennings Paul 
    Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria
  • Quantification and relationship of stress and adversity in cellular systems 
    Alice Limonciel 
    Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria
  • Inclusion of biokinetic principles and ADME as inputs for AOPs
    Nynke Kramer 
    Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands
  • Modelling the quantitative aspects of AOPs 
    Mark Cronin 
    Liverpool John Moores University, Liverpool, United Kingdom 
  • Systems biology tools for quantitative AOPs 
    Frederic Yves Bois 
    DRC/VIVA/METO, INERIS, Verleuil en Halatte, France

Session Abstract

Over the last decade the field of toxicology has become a mechanistically driven science. This has been facilitated by several key technological developments including the adoption of toxicogenomics. However, this new era of data-rich toxicology poses a problem in transitioning hazard identification to risk assessment. Indeed, for hazard identification, a chemical’s impact is simplified into two parameter dose response relationships. In reality cause and effect are much more complicated encompassing kinetics, molecular initiating events, and multiple cascading secondary events before an adverse effect can materialise. This is complicated further by innate defence mechanisms (e.g. glutathione content) and the initiation of adaptive stress responses (e.g. the Nrf2 pathway).  The documentation of this information into adverse outcome pathway constructs goes some way to help organise this information. However, within current AOP constructs quantification is lacking and kinetics is ignored. This session will lay out current challenges and potential solutions to introduce quantitation into AOP constructs in order to improve their utilisation and uptake for chemical risk assessment.
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