National Toxicology Program

National Toxicology Program

Development of a U.S. Strategy for Implementing the Vision for Toxicity Testing in the 21st Century

Discussion of the Strategy Proposal by the Scientific Advisory Committee for Alternative Toxicological Methods

A proposal for developing a Strategy for Implementing the Vision for Toxicity Testing in the 21st Century will be the main topic for discussion at the meeting of the Scientific Advisory Committee for Alternative Toxicological Methods (SACATM) on Tuesday, September 27, at the National Institute of Environmental Health Sciences, Research Triangle Park, NC

In order to realize the full potential for improving and protecting human health offered by advances in science and technology, the United States must develop a strategy for the safe, effective, and timely implementation of human-based predictive approaches for toxicity testing. The recently enacted Frank R. Lautenberg Chemical Safety for the 21st Century Act, which calls for increased use of information from alternative test methods and strategies, and the Precision Medicine Initiative, a bold new research effort to revolutionize how we improve health and treat disease, both speak to the urgent need to develop a strategy for evaluating the impact of xenobiotics on human and environmental health. A pending report from the National Academy of Sciences (NAS) on Incorporating 21st Century Science into Risk-Based Evaluations will certainly help inform future efforts.  However, developing a holistic approach for establishing confidence in these new approaches may require significant changes in policy, practice, and regulation; a challenge so complex and broad in scope that it cannot adequately be addressed by any single agency or existing government entity.  Consequently, a discussion of the best path(s) forward to address this issue needs to be started.

At their September 27 meeting, SACATM will comment on the need for a U.S. Strategy and Roadmap for implementing 21st century toxicity testing approaches, and to provide advice on the specific topics identified below as important for this effort.

  1. The historical use of animal models by regulated industries, coupled with the institutionalized use of animal-based data as the “gold standard” against which all new methods must be compared, could impede the validation and adoption of human-based methods and approaches that may be cheaper, faster, and more physiologically relevant. There exists an urgent need to identify and understand informative animal models, while also developing a scientific framework for validating more human-relevant (non-animal) methods.
    • Traditional approaches to validation often rely on comparing data obtained from a new method/strategy with results from an existing animal-based test. This becomes problematic for toxicity tests that have species-specific biases and also precludes any new test from performing “better” than the animal test, as any discordance will be assessed in favor of the existing method. In the absence of sufficient human data, how can new methods be validated as having equivalent (or better) performance than the animal-based test without a direct comparison to data from the animal test intended for replacement?
    • Is there a place in our current paradigms to begin to apply a fundamental non-animal strategy that allows prospective validation without compromising near term human safety?
  2. The utilization of human data will be an essential component of future validation efforts needed to establish confidence in new approaches for screening, prioritization and testing. Therefore, mechanisms for the ethical collection and sharing of data derived from human subjects exposed to xenobiotics need to be addressed.
    • What obstacles currently prevent the collection and use of human toxicological data and what are some potential solutions to facilitate the use of human data in the future?
  3. Increased strategic coordination amongst and between Federal agencies and stakeholders (including international partners) would improve scientific and fiscal efficiency, providing greater return on investments while expediting the development and utilization of new technologies.
    • What strategies and mechanisms could be employed to increase communication and coordination of activities amongst and between the federal government and key stakeholders?
  4. While advancements in science and technology are essential to the development of 21st century approaches, there a number of “non-scientific” considerations (e.g., political, institutional, international, social, ethical, trade, policy, education, training, and legal challenges) that could impede the adoption and implementation of such approaches. These issues must be delineated and addressed as part of a comprehensive implementation plan.
    • What are the most important “non-scientific” issues and how should they be prioritized?
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.