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An Evolving View of Quantitative Adverse Outcome Pathways and Considerations for Application
Citation:
Villeneuve, Dan. An Evolving View of Quantitative Adverse Outcome Pathways and Considerations for Application. ECETOC WORKSHOP ON QUANTITATIVE RESPONSE-RESPONSE RELATIONSHIPS (QAOPS), NA, MN, October 18 - 19, 2022. https://doi.org/10.23645/epacomptox.21423882
Impact/Purpose:
Presentation to the Centre for Chemical Safety Assessment (ECETOC) Workshop on Quantitative Response-Response Relationships (QAOPS) October 2022. Adverse outcome pathways are intended to summarize the scientifically-credible basis for extrapolating effects measured at the molecular/cellular/biochemical level of organization to hazards at higher levels of biological organization that are relevant to risk assessment. While it is helpful to establish that connection at a qualitative level, many regulatory decision-making contexts require the ability to determine the probability or severity of effect for a given exposure scenario. This presentation highlights previous approaches to support quantitative extrapolation along a toxicological pathway. It also identifies the limitations associated with a research intensive approach of biologically-based model development and proposes some alternative methods that are being investigated. Acceleration of the pace of quantitative adverse outcome pathway development could help increase the uptake of new approach methodologies for chemical safety assessment.
Description:
Quantitative adverse outcome pathways (qAOPs) have been broadly defined as AOPs for which the quantitative understanding of the key event relationships is sufficient to allow for estimation of the probability or severity of the adverse outcome occurring based on measured or modeled changes in an early key event in the pathway. This presentation will report on testing and evaluation of an early example of a qAOP based on a system of interconnected, mechanistically-based, computational models. Recognizing that the pace of similar qAOP development has not been sufficient to support the growing interest in application of new approach methodologies in chemical safety decision-making, we consider alternative ways to develop qAOPs. For example, anchoring AOP development to prototypical stressors for which there is a strong database of concentration-response data across key events may provide an alternative approach. However, applying this strategy will involve testing and evaluation of several key assumptions to evaluate whether relationships developed for the prototypical stressor and domain of empirical evidence can be extended to the plausible domain of applicability for the AOP. The contents of this abstract neither constitute, nor necessarily reflect, US EPA policy.
URLs/Downloads:
DOI: An Evolving View of Quantitative Adverse Outcome Pathways and Considerations for Application
VILLENEUVE_ECETOC-QAOP WORKSHOP OCTOBER 18 2022_V3.PDF (PDF, NA pp, 2591.897 KB, about PDF)