Heinrich Heine University, 40225, Düsseldorf, Germany.
IUF - Leibniz Research Institute for Environmental Medicine 40225, Düsseldorf, Germany.
Toxicol Sci. 2018 Sep 1;165(1):21-30. doi: 10.1093/toxsci/kfy178.
There is evidence that chemical exposure during development can cause irreversible impairments of the human developing nervous system. Therefore, testing compounds for their developmentally neurotoxic potential has high priority for different stakeholders: academia, industry, and regulatory bodies. Due to the resource-intensity of current developmental neurotoxicity (DNT) in vivo guidelines, alternative methods that are scientifically valid and have a high predictivity for humans are especially desired by regulators. Here, we review availability of stem-/progenitor cell-based in vitro methods for DNT evaluation that is based on the concept of neurodevelopmental process assessment. These test methods are assembled into a DNT in vitro testing battery. Gaps in this testing battery addressing research needs are also pointed out.
有证据表明,发育过程中的化学暴露会导致人类发育中的神经系统不可逆转的损伤。因此,测试化合物的发育神经毒性潜力是学术界、工业界和监管机构等不同利益相关者的首要任务。由于目前体内发育神经毒性(DNT)指南的资源密集型性质,监管机构特别希望获得具有科学有效性和高度人类预测性的替代方法。在这里,我们回顾了基于神经发育过程评估概念的用于 DNT 评估的基于干细胞/祖细胞的体外方法的可用性。这些测试方法被组装成 DNT 体外测试电池。还指出了该测试电池在解决研究需求方面存在的差距。