CAAT, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
ALTEX. 2011;28(2):83-93. doi: 10.14573/altex.2011.2.083.
The report by the National Research Council of the US National Academy of Sciences, Toxicity Testing in the 21st Century: A Vision and a Strategy, has prompted a discussion about renewing regulatory toxicology - especially for chemicals - by harnessing in vitro tests, in silico approaches, and testing in lower organisms. The key change is basing the assessments on mechanisms and toxicant modes of action. Identifying pathways of toxicity (PoT), especially on a larger scale, evidently requires omics technologies. When the PoT is known, a test battery allowing higher throughput than the current approach can be constructed. Here, we propose an extension of this concept to mapping the entirety of PoT in humans: the human toxome. Mapping the human toxome will allow us, for the first time, to conclusively identify substances as nontoxic or to identify nontoxic concentrations of substances (i.e., concentrations at which no relevant PoT are triggered). The concept is explained, and opportunities and obstacles are discussed, aiming to promote an initiative which will form the core of a Human Toxicology Project to implement Toxicology for the 21st Century.
美国国家科学院国家研究理事会的报告《21 世纪的毒理学测试：愿景与策略》引发了一场关于通过体外测试、计算方法和低等生物测试来更新监管毒理学——尤其是针对化学物质的监管毒理学——的讨论。关键的变化是基于机制和毒物作用模式来进行评估。确定毒性途径（PoT），尤其是在更大的规模上，显然需要组学技术。当知道了 PoT 后，就可以构建一个比当前方法具有更高通量的测试组合。在这里，我们提出将这一概念扩展到人类毒性途径的整体映射：人类毒体组。绘制人类毒体组图谱将使我们首次能够确定物质是否无毒，或者确定物质的无毒浓度（即没有触发任何相关毒性途径的浓度）。本文解释了这一概念，并讨论了其中的机会和障碍，旨在推动一项倡议，该倡议将构成实施 21 世纪毒理学的人类毒理学项目的核心。
