Pragmatic Challenges for the Vision of Toxicity Testing in the 21st Century in a Regulatory Context: Another Ames Test? …or a New Edition of “the Red Book”?
Critical review highlights regulatory hurdles in chemical toxicity testing, suggesting pragmatic bridging strategies are needed to distinguish biological from adverse effects.
Key Points
To critically evaluate the National Research Council's vision for 21st-century toxicity testing and identify practical barriers to its adoption in regulatory risk assessment.
Reviewed the 2006, 2007, and 2008 National Research Council reports alongside subsequent implementation strategies for modernizing toxicity evaluations.
Evaluated high-throughput pathway perturbation concepts against regulatory definitions of adversity, existing international chemical management frameworks, and science policy default assumptions.
The proposed 21st-century framework fails to clearly differentiate between reversible adaptive cellular perturbations and true adverse apical health outcomes.
Implementation lacks short-term bridging strategies that leverage existing toxicological and exposure prioritization data from international programs like those in Canada and Europe.
Pervasive regulatory reliance on conservative default assumptions presents a major institutional disincentive to adopting mechanistic pathway-based testing alternatives.