Bolon Brad, Garman Robert, Jensen Karl, Krinke Georg, Stuart Barry
GEMpath Inc., Cedar City, Utah 84720, USA.
Toxicol Pathol. 2006;34(3):296-313. doi: 10.1080/01926230600713269.
A key trait of developmental neurotoxicants is their ability to cause structural lesions in the immature nervous system. Thus, neuropathologic assessment is an essential element of developmental neurotoxicity (DNT) studies that are designed to evaluate chemically-induced risk to neural substrates in young humans. The guidelines for conventional DNT assays have been established by regulatory agencies to provide a flexible scaffold for conducting such studies; recent experience has launched new efforts to update these recommendations. The present document was produced by an ad hoc subcommittee of the Society of Toxicologic Pathology (STP) tasked with examining conventional methods used in DNT neuropathology in order to define the 'best practices' for dealing with the diverse requirements of both national (EPA) and international (OECD) regulatory bodies. Recommendations (including citations for relevant neurobiological and technical references) address all aspects of the DNT neuropathology examination: study design; tissue fixation, collection, processing, and staining; qualitative and quantitative evaluation; statistical analysis; proper control materials; study documentation; and personnel training. If followed, these proposals will allow pathologists to meet the need for a sound risk assessment (balanced to address both regulatory issues and scientific considerations) in this field today while providing direction for the research needed to further refine DNT neuropathology 'best practices' in the future.
发育神经毒物的一个关键特性是它们能够在未成熟的神经系统中造成结构性损伤。因此，神经病理学评估是发育神经毒性（DNT）研究的一个基本要素，这些研究旨在评估化学物质对年轻人类神经基质造成的风险。监管机构已经制定了常规DNT检测的指导方针，为开展此类研究提供一个灵活的框架；最近的经验促使人们做出新的努力来更新这些建议。本文档由毒理病理学会（STP）的一个特设小组委员会编写，该小组委员会的任务是审查DNT神经病理学中使用的传统方法，以便确定应对国家（美国环境保护局）和国际（经济合作与发展组织）监管机构的各种要求的“最佳实践”。建议（包括相关神经生物学和技术参考文献的引用）涵盖了DNT神经病理学检查的各个方面：研究设计；组织固定、收集、处理和染色；定性和定量评估；统计分析；合适的对照材料；研究记录；以及人员培训。如果遵循这些建议，病理学家将能够满足当今该领域进行合理风险评估（在平衡解决监管问题和科学考量方面）的需求，同时为未来进一步完善DNT神经病理学“最佳实践”所需的研究提供指导。
