Juberg Toxicology Consulting LLC, Indianapolis, IN, USA.
DAFoxTox Consulting, Austin, TX, USA.
Regul Toxicol Pharmacol. 2023 Sep;143:105444. doi: 10.1016/j.yrtph.2023.105444. Epub 2023 Jul 11.
For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB). SciPinion convened an expert panel to address specific questions related to the interpretation of in vitro DNT test data. The consensus of the expert panel was that the DNT IVB might be used during initial screening, but it is not presently a complete or surrogate approach to determine whether a chemical is a DNT in humans. By itself, the DNT IVB does not have the ability to capture nuances and complexity of the developing nervous system and associated outcomes including behavioral ontogeny, motor activity, sensory function, and learning/memory. Presently, such developmental landmarks cannot be adequately assessed in the DNT IVB or by other NAMs. The expert panel (all who serve as co-authors of this review) recommended that additional data generation and validation is required before the DNT IVB can be considered for application within global regulatory frameworks for decision-making.
几十年来，人们越来越关注与化学物质相关的潜在发育神经毒性（DNT）。监管机构历来利用标准化的体内测试来评估 DNT。由于包括高通量筛选 DNT、减少动物使用和潜在的成本效益等考虑因素，替代新方法（NAM）的发展应运而生；具体而言，体外发育神经毒性测试组合（DNT IVB）的出现。SciPinion 召集了一个专家小组，以解决与体外 DNT 测试数据解释相关的具体问题。专家组的共识是，DNT IVB 可用于初步筛选，但目前它不是确定化学物质是否对人类具有发育神经毒性的完整或替代方法。仅凭 DNT IVB 本身，它无法捕捉到发育中神经系统及其相关结果（包括行为发生、运动活动、感觉功能和学习/记忆）的细微差别和复杂性。目前，DNT IVB 或其他 NAMs 均无法充分评估这些发育里程碑。专家组（均为本综述的共同作者）建议，在 DNT IVB 可用于全球监管框架中的决策制定之前，需要进行额外的数据生成和验证。
