Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity.
Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity.
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DOI：
10.1016/j.tiv.2018.06.009
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Jarabek AM
中科院分区：
文献类型：
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作者：
Clippinger AJ;Allen D;Behrsing H;BéruBé KA;Bolger MB;Casey W;DeLorme M;Gaça M;Gehen SC;Glover K;Hayden P;Hinderliter P;Hotchkiss JA;Iskandar A;Keyser B;Luettich K;Ma-Hock L;Maione AG;Makena P;Melbourne J;Milchak L;Ng SP;Paini A;Page K;Patlewicz G;Prieto P;Raabe H;Reinke EN;Roper C;Rose J;Sharma M;Spoo W;Thorne PS;Wilson DM;Jarabek AM
需要新的方法来评估吸入物质对人类健康的影响。这些方法将基于毒性机制、对剂量测定的理解以及计算机建模和体外测试方法的使用。在实施这些方法之前，需要开发不良结果途径（AOP），识别和解决我们对模型输入和机制相关参数的理解中的差距，并优化可用于调查这些AOP中关键事件的非动物方法。本文描述了可用于评估吸入暴露后导致毒性的关键事件的AOP和体外和计算机模型工具箱。由于最佳的测试策略将根据感兴趣的物质而有所不同，在这里，我们提出了一种决策树方法来确定适当的非动物综合测试策略，该策略包括考虑物质的理化性质，相关的毒性机制，以及可用的计算机模型和体外测试方法。该决策树可以促进测试方法的标准化。案例研究的例子提供了一个基础的概念验证测试，以说明非动物的方法来预测吸入物质对人类的危害的效用。
New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. Before these approaches can be implemented, there is a need to develop adverse outcome pathways (AOPs), identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events in these AOPs. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance’s physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to predict the hazard to humans of inhaled substances.
影响因子：
4.1
作者：
Allen, Timothy E. H.;Goodman, Jonathan M.;Russell, Paul J.
通讯作者：
Russell, Paul J.
影响因子：
4.1
作者：
Ankley, Gerald T.;Bennett, Richard S.;Villeneuve, Daniel L.
通讯作者：
Villeneuve, Daniel L.