Toxicity Pathways – from concepts to application in chemical safety assessment

Few would deny that the NRC report (NRC, 2007), "Toxicity Testing in the 21st Century: A Vision and Strategy”, represented a re-orientation of thinking surrounding the risk assessment of environmental chemicals. The key take-home message was that by understanding Toxicity Pathways (TP) we could profile the potential hazard and assess risks to humans and the environment using intelligent combinations of computational and in vitro methods. In theory at least, shifting to this new paradigm promises more efficient, comprehensive and cost effective testing strategies for every chemical in commerce while minimising the use of animals. For those of us who embrace the vision and the strategy proposed to achieve it, attention has increasingly focused on how we can actually practice what we preach. For a start, 21st century concepts described in the report have to be carefully interpreted and then translated into processes that essentially define and operationalize a TP framework for chemical risk assessment. In September 2011 the European Commission's Joint Research Centre (JRC) and the Hamner Institutes for Health Sciences co-organised a "Toxicity Pathways" workshop. It was hosted by the JRC and took place in Ispra, Italy. There were 23 invited participants with more or less equal representation from Europe and North America. The purpose of the meeting was to address three key questions surrounding a TP based approach to chemical risk assessment, namely – What constitutes a TP? How can we use TPs to develop in vitro assays and testing strategies? And, How can the results from TP testing be used in human health risk assessments? The meeting ran over two days and comprised a series of thought-starter presentations, breakout sessions and plenty of group discussions. The outcome was captured by rapporteurs and compiled as a workshop report which is available for download (without charge) from the JRC website. Here we expand on selected deliberations of the workshop to illustrate how TP thinking is still evolving and to indicate what pieces of the puzzle still need to fall into place before TP based risk assessment can become a reality.JRC.I.5-Systems Toxicolog