As complex mixtures, botanicals present unique challenges when assessing safe use, particularly when endpoint gaps exist that cannot be fully resolved by existing toxicological literature. Here we explore in vitro gene expression as well receptor binding and enzyme activity as alternative assays to inform on developmental and reproductive toxicity (DART) relevant modes of action, since DART data gaps are common for botanicals. Specifically, botanicals suspected to have DART effects, in addition to those with a significant history of use, were tested in these assays. Gene expression changes in a number of different cell types were analysed using the connectivity mapping approach (CMap) to identify modes of action through a functional read across approach. Taken together with ligand affinity data obtained using a set of molecular targets customised towards known DART relevant modes of action, it was possible to inform DART risk using functional analogues, potency comparisons and a margin of internal exposure approach.

作为复杂的混合物，植物药在评估安全使用时会面临独特的挑战，尤其是当存在现有毒理学文献无法完全解决的终点空白时。在这里，我们探讨了体外基因表达以及受体结合和酶活性，作为替代测定法来告知发育和生殖毒性（DART）相关的作用方式，因为DART数据缺口对于植物药是常见的。具体而言，在这些分析中还测试了除了具有重要使用历史的植物以外，还怀疑具有DART作用的植物。使用连接映射方法（CMap）分析了许多不同细胞类型中的基因表达变化，以通过跨功能的方法识别作用方式。