Developmental toxicity is defined as the occurrence of adverse effects on the developing organism as a result from exposure to a toxic agent. These alterations can have long-term acute effects. Current in vitro models present important limitations and the evaluation of toxicity is not entirely objective. In silico methods have also shown limited success, in part due to complex and varied mechanisms of action that mediate developmental toxicity, which are sometimes poorly understood. In this article, we compiled a dataset of compounds with developmental toxicity categories and annotated mechanisms of action for both toxic and non-toxic compounds (DVTOX). With it, we selected a panel of protein targets that might be part of putative Molecular Initiating Events (MIEs) of Adverse Outcome Pathways of developmental toxicity. The validity of this list of candidate MIEs was studied through the evaluation of new drug-target relationships that include such proteins, but were not part of the original database. Finally, an orthology analysis of this protein panel was conducted to select an appropriate animal model to assess developmental toxicity. We tested our approach using the zebrafish embryo toxicity test, finding positive results.

中文翻译：

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用于收集和预测发育毒性中分子引发事件的计算方法。

发育毒性被定义为由于暴露于有毒物质而对发育中生物产生的不利影响。这些改变会产生长期的急性影响。当前的体外模型存在重要的局限性，毒性的评估也不是完全客观的。计算机方法也显示出有限的成功，部分是由于介导发育毒性的复杂而多样的作用机理，有时人们对此知之甚少。在本文中，我们编辑了具有发育毒性类别的化合物数据集，并注明了有毒和无毒化合物（DVTOX）的作用机理。有了它，我们选择了一组蛋白质靶标，这些靶标可能是发育毒性的不良结果途径的推定分子引发事件（MIE）的一部分。通过评估包括此类蛋白质但不属于原始数据库的新药物-靶标关系，研究了该候选MIE列表的有效性。最后，对该蛋白质组进行了正畸分析，以选择合适的动物模型来评估发育毒性。我们使用斑马鱼胚胎毒性测试测试了我们的方法，发现了积极的结果。