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

潜在致敏物危险识别的体外技术对NIEHS越来越重要。与商业供应商签订了研究合作协议，以评估GARDair检测试剂盒在识别呼吸道致敏物方面的效用。作为先前报告的机构伙伴研究的延伸，其中使用体外方法评估了200多种化学品，以评估其诱导皮肤致敏的潜力，NIEHS要求伙伴机构提名，以评估使用体外方法评估化学品诱导肺部过敏反应的潜力。 GARDair检测试剂盒使用了一个有可能识别呼吸道致敏物的基因集。机构合作伙伴共提名了100种化学品进行测试，包括已知的呼吸道致敏剂以及未知的致敏潜力的化学品。BRT在2023财年完成了化学品的采购，实验室研究正在进行中。到目前为止，已有20种化学品通过了测距仪的检测，并完成了主要试验。NIEHS资助BRT参与亲电子过敏原筛查试验（EASA）的验证试验。 本试验在无细胞评估中使用非蛋白质/肽探针，以测量供试品与生物学重要分子“反应”的能力，用于鉴定亲电性过敏性接触性皮炎危害。这些化学品的数据收集于2022财年完成，研究方法转移和验证报告于2023财年完成并关闭。

In vitro techniques for hazard identification for potential sensitizers have been of increasing importance to the NIEHS. A research collaboration agreement with a commercial vendor was established to assess the utility of the GARDair assay to identify respiratory sensitizers. As an extension of the previously reported agency partner studies where >200 chemicals were evaluated using in vitro methods to assess their potential to induce skin sensitization, NIEHS requested nominations from partner agencies to evaluate the use of an in vitro method to evaluate chemicals for their potential to induce allergic responses in the lung. The GARDair assay uses a gene set that has potential for identifying respiratory sensitizers. Agency partners nominated a total of 100 chemicals to be tested, including known respiratory sensitizers as well as chemicals of unknown potential to induce sensitization. BRT completed procurement of the chemicals in FY23 and the laboratory studies are ongoing. To date, 20 chemicals have passed range finder assays and the main runs are completed. NIEHS funded BRT participation in validation trials for the Electrophilic Allergen Screening Assay (EASA). This assay uses non-protein/peptide probes in a cell-free assessment to measure the ability of a test substance to “react” with biologically important molecules for the identification of electrophilic allergic contact dermatitis hazards. Data collection for these chemicals was completed in FY22 and the study method transfer and validation reports were completed and closed in FY23.