In-Vitro Toxicology Unit/European Centre for the Validation of Alternative Methods, Institute of Health and Consumer Protection, European Commission Joint Research Centre, TP 580, Via Fermi 1; 21020 Ispra (VA), Italy.
Neurotoxicol Teratol. 2010 Jan-Feb;32(1):36-41. doi: 10.1016/j.ntt.2008.12.003. Epub 2008 Dec 24.
The current testing requirements for both adult and developmental neurotoxicity evaluation are based on in vivo animal models and the neurotoxic potency of compounds is mainly determined by neurobehavioural and neuropathological effects. In vitro studies are considered complementary to animal tests because they provide an understanding of the molecular/cellular mechanisms involved in neurotoxicity. However, the selection of relevant in vitro neuronal/glial specific endpoints applied to various neuronal cellular models should be done in a careful way to build reliable and feasible testing strategies since usually these endpoints have to be tested in various complementary in vitro systems. The requirements for applying a more complex test strategy where toxicokinetic aspects are included together with different tools to compensate for the lack of in vitro metabolic competence are discussed. Taking into consideration the recent European Commission chemical legislation concerning registration, evaluation and authorisation of chemicals (REACH) it has become a priority to develop new intelligent testing strategies integrating computational models and in vitro assays based on cell culture models and endpoints that are amenable for adaptation to high throughput screening to be able to test a large number of chemicals.
当前，成人和发育神经毒性评估的测试要求基于体内动物模型，化合物的神经毒性效力主要由神经行为和神经病理学效应来确定。体外研究被认为是动物试验的补充，因为它们可以了解神经毒性相关的分子/细胞机制。然而，应该谨慎选择适用于各种神经元细胞模型的相关体外神经元/神经胶质特异性终点，以建立可靠且可行的测试策略，因为这些终点通常需要在各种互补的体外系统中进行测试。本文讨论了应用更复杂的测试策略的要求，其中包括毒性动力学方面以及不同的工具，以弥补体外代谢能力的不足。考虑到最近欧洲委员会关于化学品注册、评估和授权的法规 (REACH)，开发新的智能测试策略已成为当务之急，该策略整合了基于细胞培养模型和适用于高通量筛选的体外测定的计算模型，以能够测试大量的化学品。
