There are many mechanisms of neurotoxicity that are initiated by the interaction of chemicals with different neurological targets. Under the U.S. Environmental Protection Agency's ToxCast program, the biological activity of thousands of chemicals was screened in biochemical and cell-based assays in a high-throughput manner. Two hundred sixteen assays in the ToxCast screening database were identified as targeting a total of 123 proteins having neurological functions according to the Gene Ontology database. Data from these assays were imported into the Organization for Economic Co-operation and Development QSAR Toolbox and used to predict neurological targets for chemical neurotoxins. Two sets of data were generated: one set was used to classify compounds as active or inactive and another set, composed of AC₅₀s for only active compounds, was used to predict AC₅₀ values for unknown chemicals. Chemical grouping and read-across within the QSAR Toolbox were used to identify neurologic targets and predict interactions for pyrethroids, a class of compounds known to elicit neurotoxic effects in humans. The classification prediction results showed 79% accuracy while AC₅₀ predictions demonstrated mixed accuracy compared with the ToxCast screening data.

中文翻译：

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使用ToxCast体外数据在计算机上鉴定化学神经毒素的蛋白质靶标，并在QSAR工具箱中交叉读取†

化学物质与不同神经系统靶标的相互作用引发了许多神经毒性机制。根据美国环境保护署的ToxCast计划，以高通量的方式在生物化学和基于细胞的测定中筛选了数千种化学物质的生物活性。根据基因本体论数据库，ToxCast筛选数据库中的216种测定被鉴定为靶向总共123种具有神经功能的蛋白质。这些测定的数据被导入到经济合作与发展组织QSAR Toolbox中，并用于预测化学神经毒素的神经学靶标。生成了两组数据：一组用于将化合物分类为有活性或无活性，另一组由AC ₅₀组成s仅用于活性化合物，用于预测未知化学物质的AC ₅₀值。QSAR工具箱中的化学分组和交叉读取可用于识别神经系统靶标并预测拟除虫菊酯的相互作用，拟除虫菊酯是一类已知在人类中引起神经毒性作用的化合物。与ToxCast筛选数据相比，分类预测结果显示了79％的准确性，而AC ₅₀预测显示了混合的准确性。