AXLR8

Accelerating the transition to a toxicity pathway-based paradigm for chemical safety assessment through internationally coordinated research and technology development

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 Obiettivo del progetto (Objective)

'Conventional approaches to toxicity testing and risk assessment are often decades old, costly and low-throughput, and of dubious relevance to humans. These factors have prompted leading scientific bodies to call for a transition to a 21st century paradigm, including a move away from apical outcomes at high doses in whole animals, and toward a mechanistic understanding of the source-to-outcome continuum between xenobiotic exposure and adverse health effects. Such a shift will require a robust understanding of the cellular response/toxicity pathways which that can lead to adverse effects when perturbed; appropriate in vitro systems to study chemical interactions at key targets along a pathway; and computational systems biology models to describe the “circuitry” underlying each pathway as a basis for creating biologically realistic dose-response models. The AXLR8 project aims to support the transition to a toxicity pathway-based paradigm for quantitative risk assessment, and to this end will: 1) Organise a series of scientific workshops and expert meetings to map and catalogue research progress, gaps and needs in the above areas. 2) Provide a range of tools and opportunities for enhanced interdisciplinary and international communication, coordination and collaboration in order to maximise the impact of available resources. 3) Work to streamline regulatory acceptance procedures to provide for the expeditious uptake of validated 3Rs methods, including a smooth transition to 21st century systems as they become available. 4) Produce an authoritative report on the state of the science, including a practical roadmap detailing priority research and funding targets, in order to ensure a prominent role for European science in this rapidly developing global research area.'

Introduzione (Teaser)

Chemical toxicity testing is inefficient, expensive, heavily reliant on animals and consequently not directly applicable to human exposure. Numerous projects addressing these issues came together for major future impact.

Descrizione progetto (Article)

Chemicals improve the quality of our lives whether through direct use in pharmaceuticals or through the numerous products in which chemical compounds are incorporated. However, we currently lack the appropriate tools to analyse toxicity quickly, cost effectively and in a way that is directly relevant to human exposure.

The EU is currently funding numerous research projects aimed at better understanding of the chemical pathways and cellular mechanisms of toxicity. The goal is to enable automated, human cell line-based in vitro testing for high-throughput and directly interpretable analyses.

EU funding of the project http://axlr8.eu (AXLR8) enabled the establishment of a focal point for coordination of these efforts.

AXLR8 organised annual workshops, roundtable discussions and informational forums. It also served as a bridge between end users and test developers to ensure industry needs and regulatory requirements are met. Having collected information on the latest progress, the team produced annual reports with recommendations concerning funding priorities for rapid and focused achievement of goals. The consortium developed tools, encouraged networking and enhanced public awareness.

Effective collaboration, harmonisation and monitoring of research endeavours at national, European and international levels to enable 100% human cell line-based toxicity testing is critical to success. AXLR8 has effectively laid the groundwork for that transition, establishing a coordinated effort and pointing the way to research funding priorities for Horizon 2020.

Project research itself has led to numerous scientific publications in peer-reviewed journals. The vision for elimination of animal testing while significantly enhancing the efficiency and effectiveness of analyses is on its way to becoming a reality.