STUDIES TO EVALUATE THE POTENTIAL FOR ENVIRONMENTAL&THERAPEUTIC AGENTS TO INDUCE IMMUNOTOXICITY - In vitro immunomodulation

潜在致敏剂的体外危险识别技术对NTP越来越重要。在22财年，BRT重点报告了由机构合作伙伴提名的化学品的数据。NTP与EPA、CSPC、FDA和其他联邦机构合作，编制了一份227种化学品的清单，用于体外测试可能导致敏化和过敏的可能性。这些化合物的提名是基于体内数据的可用性，以探索几种体外方法的适用范围，包括：1)DPRA-直接肽反应试验；2)角蛋白-角质形成细胞激活；以及3)h-clat-人类细胞系激活试验。这些检测作为NTP体外测试电池的工具箱，用于评估化学物质引起敏化的可能性。NTP已经收到了5份来自这些体外研究的最终报告，并已与机构间的合作者分享。建立了一项合作研究，以调查GARDSkin试验的适用范围。这项测试使用基因表达谱来区分皮肤敏感者和非敏感者。在这个项目中，总共测试了31种化学品。NTP机构合作伙伴正在审查这些数据，一份报告正在编写中。在22财年，NTP要求BRT作为独立的验证实验室加入EASA的验证试验。验证团队向BRT提供了总共20种编码的化学物质，并在盲法下使用EASA分析方法进行了分析。这些化学品的数据收集工作已经完成，并向验证小组提交了一份报告草稿。这项测试是对体外超敏反应评估工具箱的一个有价值的补充。

In vitro techniques for hazard identification for potential sensitizers have been of increasing importance to the NTP. In FY22, BRT focused on reporting out the data for chemicals nominated by agency partners. The NTP, in collaboration with the EPA, CSPC, FDA and other federal agencies, had compiled a list of 227 chemicals for in vitro testing for the potential to cause sensitization and hypersensitivity. These compounds were nominated based on the availability of in vivo data to explore the applicability domain for several in vitro approaches including the: 1) DPRA – Direct Peptide Reactivity Assay; 2) Keratinosens – keratinocyte activation; and the 3) h-CLAT – Human cell line activation test. These assays serve as the toolbox for the NTP in vitro testing battery that is being used to evaluate the potential for chemicals to cause sensitization. The NTP has received 5 final reports from these in vitro studies which have been shared with interagency collaborators. A collaborative study was established to investigate the applicability domain for the GARDSkin assay. This assay uses gene expression profiling to discriminate skin sensitizers from non-sensitizers. A total of 31 chemicals were tested in this project. The data is under review by NTP agency partners and a report is in preparation. In FY22 BRT was asked by NTP to join the validation trial for the Electrophilic Allergen Screening Assay (EASA) as an independent validation laboratory. A total of 20 coded chemicals were provided to BRT from the validation team and were analyzed using the EASA assay under a blinded approach. Data collection for these chemicals has been completed and a draft report has been submitted to the validation team. This assay represents a valuable addition to the in vitro toolbox for hypersensitivity assessment.