PDF(Pubmed)
Abstract：
In vitro toxicology research has accelerated with the use of in silico, computational approaches and human in vitro tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput in vitro cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing in vivo testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of in vitro tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and \"roadmaps\" to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate in vitro model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.
摘要：
体外毒理学研究随着计算机的使用而加速，计算方法和人体体外组织系统，促进重大改进，评估新型消费品的安全和健康风险。分子和细胞生物学的创新已经改变了测试范式，减少对低通量动物数据的依赖，更多地使用中高通量体外细胞筛选方法。这些新的方法方法（NAM）正在其他行业部门实施，用于化学测试，筛选候选药物和原型消费品，在对可靠的需求的驱动下，与人类相关的方法。常规毒理学方法自50多年前发展以来基本上没有变化，使用高剂量，经常采用体内试验。由于代谢或暴露的差异，进行或推断动物研究的数据会遇到一些缺点。在过去的十年中，体外工具和能力的开发取得了长足的进步，未来十年的挑战将是将这些平台整合到应用产品测试中，并被监管机构接受。政府和验证机构已经启动并应用了框架和“路线图”，以支持NAM的敏捷验证和接受。与香烟相比，下一代烟草和尼古丁产品（NGP）有可能降低吸烟者的风险。这些产品包括加热但不燃烧烟草的加热烟草产品（HTPs）；蒸汽产品也称为电子尼古丁输送系统（ENDS），加热电子液体以产生可吸入的气溶胶；口腔无烟烟草产品(例如，瑞典式鼻烟）和无烟草口服尼古丁袋。随着NGP可用性的增加以及科学研究支持监管批准的要求，NAMs方法可以补充NGP的评估。这篇综述探讨了如何将NAM应用于评估NGP，突出关键考虑因素，包括使用适当的体外模型系统，部署危险识别的筛选方法，以及测试文章表征的重要性。讨论了适合目的测试和方法标准化的重要性和机会，强调行业和跨行业合作的价值。支持监管机构接受的方法的开发可能会导致实施NAM用于烟草和尼古丁NGP测试。
