{"title":"NAM:需要测试版","authors":"Denise Bloch, Philip Marx-Stoelting, Tewes Tralau","doi":"10.1016/j.cotox.2024.100490","DOIUrl":null,"url":null,"abstract":"<div><p>A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including <em>in vitro</em>, <em>in silico</em>, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of <em>in vivo</em> data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100490"},"PeriodicalIF":4.6000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202024000329/pdfft?md5=43c34608e921555b7f5665fb5635a6ef&pid=1-s2.0-S2468202024000329-main.pdf","citationCount":"0","resultStr":"{\"title\":\"NAMs: Beta testing needed\",\"authors\":\"Denise Bloch, Philip Marx-Stoelting, Tewes Tralau\",\"doi\":\"10.1016/j.cotox.2024.100490\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including <em>in vitro</em>, <em>in silico</em>, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of <em>in vivo</em> data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.</p></div>\",\"PeriodicalId\":93968,\"journal\":{\"name\":\"Current opinion in toxicology\",\"volume\":\"39 \",\"pages\":\"Article 100490\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2468202024000329/pdfft?md5=43c34608e921555b7f5665fb5635a6ef&pid=1-s2.0-S2468202024000329-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current opinion in toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2468202024000329\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468202024000329","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
针对急性全身毒性和短期毒性,已经开发出了多种新方法(NAMs),包括体外、硅学和海洋学方法。为了推进这些方法的监管实施,我们建议迫切需要在监管环境中对这些方法进行测试。将 NAMs 用于急性全身毒性和短期毒性有几个局限性,如缺乏适用领域的定义、用于验证的参考数据有偏差、缺乏对动力学过程和多器官复杂性的表征。这些局限性可能会导致与普通监管实施相关的风险,例如将方法应用于预期适用范围之外的物质,或由于缺乏机理信息或动力学考虑而降低预测性。我们认为可以通过 beta 版测试来避免这种情况。beta 版测试的进一步好处是可以填补体内数据空白,并有可能改进方法的人体相关性验证。为了在不久的将来提高对 NAM 的改进、熟悉和接受程度,这种 beta 测试概念必须依赖于方法测试人员和开发人员之间的反馈回路。
A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including in vitro, in silico, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of in vivo data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.