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用于预测致癌潜力的自动化且可重复的类似读码框模型。

Automated and reproducible read-across like models for predicting carcinogenic potency.

作者信息

Lo Piparo Elena, Maunz Andreas, Helma Christoph, Vorgrimmler David, Schilter Benoît

机构信息

Chemical Food Safety Group, Nestlé Research Center, Lausanne, Switzerland.

In Silico Toxicology GmbH, Basel, Switzerland.

出版信息

Regul Toxicol Pharmacol. 2014 Oct;70(1):370-8. doi: 10.1016/j.yrtph.2014.07.010. Epub 2014 Jul 15.

Abstract

Several qualitative (hazard-based) models for chronic toxicity prediction are available through commercial and freely available software, but in the context of risk assessment a quantitative value is mandatory in order to be able to apply a Margin of Exposure (predicted toxicity/exposure estimate) approach to interpret the data. Recently quantitative models for the prediction of the carcinogenic potency have been developed, opening some hopes in this area, but this promising approach is currently limited by the fact that the proposed programs are neither publically nor commercially available. In this article we describe how two models (one for mouse and one for rat) for the carcinogenic potency (TD50) prediction have been developed, using lazar (Lazy Structure Activity Relationships), a procedure similar to read-across, but automated and reproducible. The models obtained have been compared with the recently published ones, resulting in a similar performance. Our aim is also to make the models freely available in the near future thought a user friendly internet web site.

摘要

通过商业软件和免费软件可以获得几种用于慢性毒性预测的定性(基于危害)模型,但在风险评估的背景下,为了能够应用暴露边际(预测毒性/暴露估计)方法来解释数据,定量值是必不可少的。最近已经开发出了用于预测致癌潜力的定量模型,在这一领域带来了一些希望,但这种有前景的方法目前受到以下事实的限制:所提出的程序既没有公开可用,也没有商业可用。在本文中,我们描述了如何使用lazar(惰性结构活性关系)开发了两种用于预测致癌潜力(TD50)的模型(一种用于小鼠,一种用于大鼠),lazar是一种类似于类推法但自动化且可重复的程序。将获得的模型与最近发表的模型进行了比较,结果显示性能相似。我们的目标还包括在不久的将来通过一个用户友好的互联网网站免费提供这些模型。

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