Smith Martyn T
School of Public Health, University of California, Berkeley, CA 94720, USA.
Curr Opin Toxicol. 2025 Mar;41. doi: 10.1016/j.cotox.2024.100515.
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 approaches, tests, and 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.
在评估一种化学物质是否会导致癌症或其他不良后果时,通常会考虑三条证据线:流行病学、动物生物测定和机制证据。关键特征(KCs)构成了一种统一方法的基础,用于搜索、组织和评估机制证据以支持危害识别。关键特征是有毒物质本身已确定的属性,是基于我们对毒性机制的理解而产生的。已经针对致癌物、内分泌干扰物以及生殖、肝脏、免疫和心血管有毒物质发布了关键特征。我们注意到,不同类型的有毒物质有一些共同的关键特征,而其他一些则具有高度特异性。因此,对于潜在有害的生物活性化学物质,可能存在重叠的总体关键特征,可用于预测毒理学。然而,对于主要针对特定器官的化学物质,也有明显独特的关键特征,这些独特的关键特征对于预测靶器官毒性可能尤为重要。有可能开发出能够预测有害化学物质的“总体”和“独特”关键特征的方法、测试和生物标志物。然而,鉴于人体证据的重要性,开发一套可用于分子流行病学研究中测量关键特征的生物标志物也很重要。