Hogberg Helena T, Fritsche Ellen, Gröters Sibylle, Kovi Ramesh C, Rao Deepa B, Terron Andrea, Winter Matthew J
National Institute of Environmental Health Sciences, Durham, North Carolina, USA.
SCHAT - Swiss Centre for Applied Human Toxicology, University of Basel, Basel, Switzerland.
Toxicol Pathol. 2025 Jun;53(4):305-320. doi: 10.1177/01926233251335719. Epub 2025 May 15.
The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on "New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives," organized in Spain, addressed the growing need for improved assessment of neurotoxicity. Traditional neurotoxicity assessment using in vivo animal studies are impractical for testing the substantial number of environmental chemicals that currently lack data and in the early detection of neuro-related adverse reactions in drug discovery. The NAMs, including human in vitro assays and small model organisms, have been developed for faster and cost-effective assessment of neurotoxic potential. While NAMs offer improved practicality, utility, and valuable mechanistic insights, their integration into regulatory decision-making requires robust scientific validation and technical characterization. Confidence in and regulatory application of NAMs data can be supported by mapping cellular outcomes to neuropathological findings in mammals, including humans, through the Adverse Outcome Pathway (AOP) framework, and the Integrated Approach to Testing and Assessment (IATA). Case studies presented demonstrated the application of NAMs in chemical and drug safety evaluations, focusing on developmental neurotoxicity (DNT), Parkinson's disease, and drug-induced seizures. In conjunction with in vivo toxicology studies, NAMs represent a significant step toward advancing chemical and drug toxicity assessment via hazard identification and drug screening safety assessments.
在西班牙举办的国际毒理病理学会(IATP)卫星研讨会“神经毒性评估的新方法学(NAMs)及监管视角”,探讨了改进神经毒性评估的日益增长的需求。使用体内动物研究进行传统神经毒性评估,对于测试目前缺乏数据的大量环境化学品以及在药物研发中早期检测神经相关不良反应而言并不实用。包括人体体外试验和小型模式生物在内的新方法学已被开发出来,用于更快速且具成本效益地评估神经毒性潜力。虽然新方法学提供了更高的实用性、效用及有价值的机制性见解,但将它们整合到监管决策中需要强有力的科学验证和技术特性描述。通过不良结局途径(AOP)框架以及测试与评估综合方法(IATA),将细胞结果映射到包括人类在内的哺乳动物的神经病理学发现,可支持对新方法学数据的信心及监管应用。所展示的案例研究证明了新方法学在化学品和药物安全性评估中的应用,重点关注发育性神经毒性(DNT)、帕金森病和药物性癫痫发作。与体内毒理学研究相结合,新方法学是通过危害识别和药物筛选安全性评估推进化学品和药物毒性评估的重要一步。
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