STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity.
STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity.
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DOI：
10.1289/ehp9341
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发表时间：
2022-03
影响因子：
10.4
通讯作者：
Tropsha A
中科院分区：
文献类型：
--
作者：
Borba JVB;Alves VM;Braga RC;Korn DR;Overdahl K;Silva AC;Hall SUS;Overdahl E;Kleinstreuer N;Strickland J;Allen D;Andrade CH;Muratov EN;Tropsha A
现代化学毒理学正面临着减少、改进和取代动物试验的日益增长的需求。用于农药、药品或化妆品中化学品急性毒性评估的最常见的动物试验类型被称为“6包”试验组，包括三个局部（皮肤致敏、皮肤刺激和腐蚀以及眼睛刺激和腐蚀）和三个全身（急性口服毒性、急性吸入毒性和急性皮肤毒性）终点。据我们所知，我们编译，策划和整合了最大的公开数据集，并为所有六个终点开发了一个定量构效关系（QSAR）模型。根据经济合作与发展组织（OECD）QSAR原则，使用未包含在训练集中的化合物数据对所有模型进行验证。除了通过交叉验证评估的高内部准确性外，所有模型都表现出70%至77%的外部正确分类率。我们建立了一个可公开访问的全身和局部化学毒性（STopTox）门户网站（https：//stoptox.mml.unc.edu/），整合了所有开发的6包检测模型。我们开发了STopTox，这是一个全面的计算模型集合，可用作体内6包测试的替代方法，用于预测小有机分子的毒性危害。模型是按照开发和验证定量构效关系模型的最佳做法建立的。科学家和监管机构可以使用STopTox门户网站在感兴趣的化学品库中识别推定的有毒或无毒物质。https://doi.org/10.1289/EHP9341
Modern chemical toxicology is facing a growing need to Reduce, Refine, and Replace animal tests for hazard identification. The most common type of animal assays for acute toxicity assessment of chemicals used as pesticides, pharmaceuticals, or in cosmetic products is known as a “6-pack” battery of tests, including three topical (skin sensitization, skin irritation and corrosion, and eye irritation and corrosion) and three systemic (acute oral toxicity, acute inhalation toxicity, and acute dermal toxicity) end points. We compiled, curated, and integrated, to the best of our knowledge, the largest publicly available data sets and developed an ensemble of quantitative structure–activity relationship (QSAR) models for all six end points. All models were validated according to the Organisation for Economic Co-operation and Development (OECD) QSAR principles, using data on compounds not included in the training sets. In addition to high internal accuracy assessed by cross-validation, all models demonstrated an external correct classification rate ranging from 70% to 77%. We established a publicly accessible Systemic and Topical chemical Toxicity (STopTox) web portal (https://stoptox.mml.unc.edu/) integrating all developed models for 6-pack assays. We developed STopTox, a comprehensive collection of computational models that can be used as an alternative to in vivo 6-pack tests for predicting the toxicity hazard of small organic molecules. Models were established following the best practices for the development and validation of QSAR models. Scientists and regulators can use the STopTox portal to identify putative toxicants or nontoxicants in chemical libraries of interest. https://doi.org/10.1289/EHP9341