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The key characteristics concept
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DOI：10.1016/j.cotox.2024.100515.png)
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Abstract
En 中文
In evaluating whether a chemical can cause cancer or another adverse outcome, three lines of evidence are typically considered: epidemiology, animal bioassays and mechanistic evidence. The key characteristics (KCs) form the basis of a uniform approach for searching, organizing, and evaluating mechanistic evidence to support hazard identification. KCs are the established properties of the toxicants themselves and are generated from our understanding of mechanisms of toxicity. KCs have been published for carcinogens, endocrine disruptors and reproductive, liver immune and cardiovascular toxicants. We noted that several KCs were common to different types of toxicants, whereas others were highly specific. Hence, there may be overlapping umbrella KCs for potentially hazardous bioactive chemicals that could be used in predictive toxicology. There are, however, also clearly unique KCs for chemicals that primarily target a specific organ and these unique KCs could be especially important to predicting target organ toxicity. It is possible that in silico approaches, in vitro tests, and in vivo biomarkers could be developed, which predict the umbrella and unique KCs of hazardous chemicals. However, given the significance of human evidence, the development of a set of biomarkers that could be used to measure the KCs in molecular epidemiology studies is also important.
Keywords:
Carcinogens
Hazard
Risk assessment
Toxicity
AOPs
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