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Striving for 21st century toxicology – exploiting mechanistic understanding to further alternative methods

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Jan 24, 2014
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Report on how Toxicity Pathway concepts can be applied in chemical safety assessment

The US National Research Council's report (2007), "Toxicity Testing in the 21st Century: A Vision and Strategy”, represented a step-change in thinking surrounding the safety assessment of environmental chemicals. The take-home message was that by understanding toxicity in terms of Toxicity Pathways, we'll be able to use intelligent combinations of computational and in vitro methods to assess the potential hazard and risk that a chemical may pose to humans and the environment, without resorting to animal testing. Shifting to this new paradigm promises more efficient, comprehensive and cost effective testing strategies for every chemical in commerce and will provide a convincing scientific basis to move away from animal testing.  But 7 years on from the publication of the NRC landmark report, much still needs to be done to translate Toxicity Pathway concepts into safety assessment practice.

Stemming from on-going collaboration between the Joint Research Centre's European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and The Hamner Institutes for Health Sciences (NC, USA), the recently published report "Toxicity Pathways – from concepts to application in chemical safety assessment" addresses three key questions, namely

  • What constitutes a Toxicity Pathway? 
  • How can we use Toxicity Pathways to develop in vitro assays and integrated testing strategies? 
  • How can the results from Toxicity Pathway based testing serve human health risk assessments? 

Dr. Maurice Whelan, head of the Systems Toxicology Unit and EURL ECVAM, pointed out that "the report illustrates how Toxicity Pathway thinking is evolving and indicates what pieces of the puzzle still need to fall into place before a true toxicity pathway-based safety assessment framework without the use of animals can become a reality." The report draws in particular on discussions from a Toxicity Pathways workshop, organised in September 2011 by EURL ECVAM and The Hamner, which brought together 23 invited experts from Europe and North America.

“Our report remains timely as international risk assessment and toxicology communities debate new ideas regarding definitions and use of toxicity pathway and network biology concepts for making regulatory and public health decisions about chemical safety.  Adoption of cell-based, high throughput tools would signal a new era for responsible regulation and more efficient use of resources in supporting regulation.  These meetings of experts, allowing opportunity for wide-ranging discussions, will help gain clarity and consensus on the value of these tools”, noted Dr. Melvin Andersen, now the Chief Science Officer at The Hamner Institutes.