Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, CROET/L606, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Environ Toxicol Pharmacol. 2005 May;19(3):735-44. doi: 10.1016/j.etap.2004.12.035. Epub 2005 Jan 25.
To address the growing need for scientifically valid and humane alternatives to developmental neurotoxicity testing (DNT), we propose that basic research scientists in developmental neurobiology be brought together with mechanistic toxicologists and policy analysts to develop the science and policy for DNT alternatives that are based on evolutionarily conserved mechanisms of neurodevelopment. In this article we briefly review in vitro and other alternative models and present our rationale for proposing that resources be focused on adapting alternative simple organism systems for DNT. We recognize that alternatives to DNT will not completely replace a DNT paradigm that involves in vivo testing in mammals. However, we believe that alternatives will be of great value in prioritizing chemicals and in identifying mechanisms of developmental neurotoxicity, which in turn will be useful in refining and reducing in vivo mammalian tests for exposures most likely to be hazardous to the developing human nervous system.
为满足对发展神经毒性测试(DNT)的科学有效且人道替代方法日益增长的需求,我们建议将发展神经生物学领域的基础研究科学家与机制毒理学家和政策分析师聚集在一起,共同制定基于神经发育过程中进化保守机制的 DNT 替代方法的相关科学和政策。在本文中,我们简要回顾了体外和其他替代模型,并提出了我们的建议,即应将资源集中用于调整 DNT 的替代简单生物系统。我们认识到,DNT 的替代方法不会完全取代涉及哺乳动物体内测试的 DNT 范例。但是,我们相信,这些替代方法在确定化学品的优先级和识别发育神经毒性的机制方面将具有巨大的价值,而这反过来又将有助于完善和减少对最有可能对人类发育中的神经系统造成危害的暴露的体内哺乳动物测试。