New EU Initiative to ‘AXLR8’ Research in Toxicology toward a Pathway-Based Paradigm

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New EU Initiative to ‘AXLR8’ Research in Toxicology toward a Pathway-Based Paradigm

V. Cilento Johnson, Guest Science Writer

Published: April 26, 2010

The standard approach for assessing the effects of chemicals and drugs on human tissues and cells is to administer high doses of these substances to living animals until they exhibit signs of extreme toxicity. The data from these tests is then extrapolated to determine safety in humans. This traditional approach is economically expensive and time-consuming, and it entails considerable animal use and suffering. In addition, animal data is not a clear indication of how chemicals will act in humans and cannot precisely determine the human health risk. As a result, leading regulatory and scientific authorities are advocating a move toward a ’21st century’ approach to chemical safety based on tests on human cells, supplemented by computer-based computational methods.

In the ’21st century’ approach, emphasis is placed on understanding how chemicals interact with the human body’s cellular response pathways at exposure levels that are environmentally relevant. Once critical pathways are mapped, human cell-based or, in vitro, tests can be developed to study interactions at significant molecular and cellular targets along the pathways. The in vitro tests can be performed large-scale with the use of robotic automation and the data can be interpreted and combined with pharmacokinetic modeling to determine human toxicity levels.

Parallel but related efforts are being made in Europe, not as much under the banner of ’21st century toxicolgy’ but as alternatives to animal testing in terms of the 3Rs of replacement, reduction, and refinement.  A number of large-scale, integrated research projects for the formulation of new 3R test methods are presently funded by the European Commission (EC) 6th and 7th Framework Programs (FP6/FP7) for research and technology development. It is essential that 3Rs activities at the European and international levels are coordinated in order to accelerate their progression toward scientific and regulatory acceptance.

The EC’s Research Directorate General is funding an initiative termed AXLR8 (‘accelerate’) for the purpose of monitoring EU FP6/FP7-funded 3Rs research activities and related international initiatives with the aim of accelerating the transition to a toxicity pathway-based paradigm for chemical safety assessment.  AXLR8 is an initiative of the Humane Society International/United Kingdom, the Institute for Pharmacy at the Free University of Berlin, and the Centre for Advanced Research & Development on Alternative Methods at the Flemish Institute of Technological Research.

AXLR8 aims to:

  1. Monitor the progression of the European FP6/FP7 research projects on alternative testing strategies by organizing annual workshops where knowledge gaps can be identified and priorities for future research funding can be recommended. Annual progress reports from these workshops will be disseminated and will include science and technology roadmaps to assist the EC in selecting and prioritizing future research.
  2. Convene a Scientific Panel of experts who will participate in the annual workshops and can advise the AXLR8 Secretariat.
  3. Engage regulatory authorities to ensure they are consistently informed of progress at the R&D level so that regulatory considerations can be understood and communicated back to the scientists who are developing the 3Rs/21stcentury approaches to safety assessment. In this way, a foundation can be laid to promote expeditious and well-organized alternative approaches in the future.
  4. Promote increased stakeholder and public awareness concerning 21st century approaches toward safety assessment.

Says AXLR8 coordinator Professor Horst Spielmann:

“With the recent demands of new legislative programs such as the EU chemicals policy REACH, which will require safety testing of many thousands of substances in short timeframes, the limitations of current animal-based systems are becoming clear. To process the backlog of existing chemicals already in use, as well as new substances, regulators need timely access to reliable and relevant toxicity data. The EC has made an unprecedented investment in 21st century science and technology to support the development of a new generation of test methods that can deliver results in weeks instead of years, using new scientific tools to generate better information for regulators and tangible benefits for human health and environmental protection. The EU FP7 project AXLR8 will accelerate the acceptance of the new animal-free methods into regulatory safety testing at the international level.”

The AXLR8 project was officially launched on January 1, 2010 and will run for 40 months. Initial activities include preparing for the first scientific workshop (invitation-only) in Berlin in late May/early June, and a public information day to be held in conjunction with the ESTIV/EUSAAT Linz2010 conference in Linz/Austria on September 1, 2010.

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