Using 21st Century Science to Improve Risk-Related Evaluations (2017) / Chapter Skim
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Building on those efforts, the National Research Council (NRC) report Toxicity Testing in the 21st SCIENTIFIC ADVANCES Century: A Vision and a Strategy1 envisioned a future in which toxicology relied primarily on high-throughput in To approach its task, the committee assessed scienvitro assays and computational models based on human tific and technological advances in exposure science and biology to evaluate potential adverse effects of chemi- toxicology that could be integrated into and used to imcal exposures.
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First, targeted analyses focus on identify- great promise for advancing exposure science and iming selected chemicals for which standards and methods proving and refining exposure measurements and assessare available. Improved analytical methods and expanded ment.
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Virtual-tissue models can potentially help cells collected from various populations to use for toxico- in conceptualizing and integrating current knowledge logical research; large compilations of publicly available about the factors that affect key pathways and the degree biological data that can be mined to develop hypotheses to which pathways must be perturbed to activate early and about relationships between chemicals, genes, and diseas- intermediate responses in human tissues and, when more es; and genetically diverse mouse strains and alternative fully developed, in supporting risk assessments. species that can be used for toxicological research.
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• Accounting for metabolic capacity in assays. Epidemiology Current in vitro assays generally have little or no metabolic capability, and this aspect potentially constrains their The scientific advances that have propelled exposure usefulness in evaluating chemical exposures that are rep- science and toxicology onto new paths have also substanresentative of human exposures that could lead to toxicity.
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Furthermore, various biospecimens are be- or biologically similar metabolites or that they are sufing collected and stored with the underlying assumption ficiently similar in structure to have the same or similar that they will be useful in future studies; researchers in- biological activity. The method is facilitated by having volved in such future-looking collections need to seek a comprehensive database of toxicity data that is searchinput from the scientists who are developing new assays able by curated and annotated chemical structures and by so that the biospecimens can be collected and stored in a using a consistent decision process for selecting suitable way that maximizes the potential for their future use.
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Animal Toxicity Dose Data on Response POD Appropriate Analogue Identify analogues on the basis of ● Similar chemical structure Adjust on the basis ● Similar physicochemical of pharmacokinetics properties of chemical of ● Common metabolism interest and ● Common key events biological activity ● Similar gene expression Model or Apply UFs Health Chemical of PODADJ Reference Interest Value FIGURE S-1 Approach to deriving health reference values when data on similar chemicals are available. Similarity can be based on such characteristics as chemical structure, physicochemical properties, metabolism, key events in biological pathways, or gene expression; similarity of several characteristics increases confidence in the analogy.
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From page 7... ...
The committee emphasizes arise from endogenous processes, and some result from that insufficient attention has been given to analysis, inthe human experience, such as background health condi- terpretation, and integration of various data streams from tions, co-occurring chemical exposures, food and nutri- exposure science, toxicology, and epidemiology. It protion, and psychosocial stressors.
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From page 8... ...
8 Using 21st Century Science to Improve Risk-Related Evaluations ultimately for improving public health and the environment. The committee emphasizes, however, that communicating the strengths and limitations of the approaches in a transparent and understandable way will be necessary if the results are to be applied appropriately and will be critical for the ultimate acceptance of the approaches.
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