In the Spotlight
Accelerating the National Research Council “Vision” for 21st Century Toxicology
Published: November 29, 2010
The NRC report, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” proposes an approach to assessing environmental chemicals based on identifying human toxicity pathways, modeling and interpreting these pathways using cellular and computational systems, and predicting levels of human exposure that are not likely to be associated with adverse effects. Thus the NRC proposal is human-focused and not designed to predict hazards associated with high-dose studies in animals, which distinguishes the NRC vision from most other approaches to toxicity testing.
The pathway approach is expected to be implemented incrementally over the course of 10-20 years. The NRC vision foresees the need for other approaches to supplement or better interpret the results from pathway testing, especially during the early years of implementation. According to the NRC report, such “targeted testing” could involve either in vivo or in vitro approaches. Progress in advancing targeted testing (such as refining human tissue-based approaches) will be key to implementing the “vision.”
The “Human Toxicology Project” is defined by the Consortium as the research and development necessary for realizing the proposed NRC vision for 21st century toxicology. “Coordinating those efforts around the NRC vision would lead to a revolution in biological understanding and biotechnology akin to that produced by the Human Genome Project,” according to Martin Stephens of the Humane Society of the United States and coordinator of the Consortium’s workshop (also a member of the AltTox Management Team).
Speakers at the Consortium workshop, entitled “Accelerating Implementation of the National Research Council Vision for Toxicity Testing in the 21st Century,” described current programs in the US and EU (e.g., ToxCast, Tox21, AXLR8, RISK21), and proposed innovative and collaborative approaches for moving the “vision” forward. Speaker presentations are available on the Consortium’s website here. Five of the original NRC committee members participated in this workshop: Melvin Andersen, Kim Boekelheide, Gail Charnley, Daniel Krewski (committee Chair), and Martin Stephens.
Scientists and institutions in the US and Europe share a common goal in wanting to modernize toxicological testing, but they have taken different approaches. To help bridge the gap, several trans-Atlantic cooperative efforts are already in place. Maurice Whelan, Head of the Systems Toxicology Unit at the European Commission Joint Research Centre’s Institute for Health and Consumer Protection (IHCP), cited the recent research collaboration established between the US Environmental Protection Agency (EPA) and the IHCP. The common theme of this collaboration, based on sharing high-throughput toxicological profile data and data from integrated testing strategies based on computational and in vitro methods, is the shift towards a “toxicological pathway based hazard assessment.”
The workshop was attended by thought-leaders and decision-makers in the relevant sectors, and succeeded in generating highly-interactive discussions during both plenary and break-out sessions. Common themes emerged, and some of the outcomes from these interactive sessions are summarized below. Consortium members are drafting the workshop proceedings for submission to Toxicological Sciences, which will include a full description of the workshop “outcomes.”
Key workshop “outcomes” noted by AltTox staff included the following:
Need for strategic planning
- Participants identified the need for a well-developed implementation strategy so that efforts are better coordinated and effective collaborations developed. Keeping up the momentum through the development of such a plan was identified as a key factor in moving the “vision” forward. Thomas Hartung, Director of Johns Hopkins Center for Alternatives to Animal Testing, noted that the workshop participants were preaching to the converted (each other) and advised that the next meeting should be strategic where decisions and plans for progress are established. Proposals for the next steps to oversee the “vision” included: a) the development of a steering committee or management team, and b) the creation of new NRC committee to prepare a detailed “roadmap” for implementation.
- Participants agreed that the pilot project approach proposed by Mel Andersen of the Hamner Institutes for Health Sciences has merit as a means of “jump-starting” the implementation of the NRC vision. This proposal would examine the effects of data-rich chemicals on well-studied pathways, and thus capitalize on existing knowledge to assess the workings of the pathway approach in real-life case studies.
Need for better funding and resources
- The current level of funding, at least in the US, does not match the ambitious scale of the NRC vision. Implementation of “the vision” will require additional amounts and sources of funding, which means that support from Congress—with public backing—is critically important.
Need for better coordination
- Coordination of research efforts needs to be improved, including coordination between different components of the vision.
Communication issues, such as…
- Better communication and coordination of efforts with regulators were cited as important by both EU and US participants. Even within agencies the scientific and regulatory branches may not be working together. Some workshop participants felt that regulators are willing to talk about the NRC vision, but not ready to embrace it. Some suggested an incremental implementation of new methods would be more welcome.
- Greater sharing of toxicological data would support progress. Industry and pharmaceutical toxicity test data are generally not publicly available, which would benefit database and methods development.
The need for a new and sustained dynamic was endorsed by workshop participants. The proposed development of a specific plan for implementing the NRC vision is clearly the major outcome that can be advanced by the collaborative work of the Consortium and workshop participants. The “next steps” are still to be determined.
NRC report: “Toxicity Testing in the 21st Century: A Vision and a Strategy”
Human Toxicology Project Consortium website
HSUS Press Release: “Scientists, Corporations and Other Stakeholders Call for a Focused Approach to Modernizing Safety Testing of Chemicals”
Related pages on AltTox
In the Spotlight articles
Federal Agencies Collaborate on New High Throughput Toxicity Screening Initiative
Molecular Libraries Initiative: Application to Tox21 and the NIH Chemical Genomics Center
New EU Initiative to ‘AXLR8’ Research in Toxicology toward a Pathway-Based Paradigm
The Way Forward essays
Toxicity Testing in the 21st Century by Melvin Andersen, Daniel Krewski, Ellen Mantus & Lauren Zeise
The Way Forward: Alternatives – The Future is Now! by Andrew Rowan
A Paradigm Shift in Toxicity Testing is Inevitable by Kim Boekelheide
Tox21: Putting a Lens on the Vision of Toxicity Testing in the 21st Century by Christopher Austin, Robert Kavlock & Raymond Tice
ASAT: Reversing the Paradigm in Toxicity Testing! by Bart Sangster
A New Perspective on the Past, Present and Future of Toxicity Testing by Sunita Shukla
Computational Toxicology by Robert Kavlock