Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use.
Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use.
复制标题
替代测试方法的参考化合物指示化学物质的发育神经毒性（DNT）的潜力：示例列表及其选择和使用标准。
DOI：
10.14573/altex.1604201
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lein PJ
中科院分区：
文献类型：
--
作者：
Aschner M;Ceccatelli S;Daneshian M;Fritsche E;Hasiwa N;Hartung T;Hogberg HT;Leist M;Li A;Mundi WR;Padilla S;Piersma AH;Bal-Price A;Seiler A;Westerink RH;Zimmer B;Lein PJ
关于工业和环境化学品造成的发育神经毒性危害的资料很少。新的检测方法很可能基于一系列替代和补充（非动物）检测。由于DNT被认为是由化学物质对基本神经发育过程（如神经元分化、前体细胞迁移或神经元网络形成）的调节引起的，因此第一代替代DNT测试针对这些过程。这种类型的测定的优点是它们捕获具有多个靶标和作用模式的毒物。此外，模拟的过程中的测定可以链接到毒性endophenotypes，即改变神经连接，形成的基础上，在man. The审查的作者召开了一个研讨会，以确定标准的选择阳性/阴性对照，准备建议其使用，并启动设置的参考化学品的目录。对于测试的初始技术优化，鉴定了一组>50种终点特异性对照化合物。为了进一步的测试开发，提出了一个额外的“测试”组，其中包括33种被认为直接作为真正的DNT毒物的化学物质，并对每种化学物质进行了注释，以达到这些标准。用于选择试验组化学品的原始文献的表格汇编提供了有关统计程序和毒性/无毒剂量（幼崽和母鼠）的信息。提供了关于如何使用此处汇编的>100种化合物（包括阴性对照）来解决特异性、逆境和使用替代试验系统的建议。
There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes. The advantage of such types of assays is that they capture toxicants with multiple targets and modes-of-action. Moreover, the processes modelled by the assays can be linked to toxicity endophenotypes, i.e. alterations in neural connectivity that form the basis for neurofunctional deficits in man. The authors of this review convened in a workshop to define criteria for the selection of positive/negative controls, to prepare recommendations on their use, and to initiate the setup of a directory of reference chemicals. For initial technical optimization of tests, a set of >50 endpoint-specific control compounds was identified. For further test development, an additional “test” set of 33 chemicals considered to act directly as bona fide DNT toxicants is proposed, and each chemical is annotated to the extent it fulfills these criteria. A tabular compilation of the original literature used to select the test set chemicals provides information on statistical procedures, and toxic/non-toxic doses (both for pups and dams). Suggestions are provided on how to use the >100 compounds (including negative controls) compiled here to address specificity, adversity and use of alternative test systems.
DOI：
10.1177/1740774509344440
发表时间：
2009-10
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Mount DL;Feeney P;Fabricatore AN;Coday M;Bahnson J;Byington R;Phelan S;Wilmoth S;Knowler WC;Hramiak I;Osei K;Sweeney ME;Espeland MA;Look AHEAD and ACCORD Research Groups
通讯作者：
Look AHEAD and ACCORD Research Groups