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

翻译毒理学部（DTT）PAC混合物评估计划（PAC-MAP）提供了一个框架，用于使用包括广泛终点的体外/短期体内测试组合评估单个多环芳香族化合物（PAC）、定义的PAC混合物和含PAC的复杂环境样品的广度。某些PAC与广泛的毒性（致癌性、免疫毒性、生殖和发育毒性、神经毒性）和一系列复杂的作用机制相关。许多PAC与体液免疫功能抑制有关，免疫毒性已被确定为估计PAC致癌潜力的信息参数。作为预测混合物效应的潜在测试组合的一部分，我们检查了13种单独PAC和3种混合物调节抗原特异性抗体应答和影响骨髓细胞学的潜力。 2023财年未启动体内免疫毒理学研究，工作重点是报告/存档之前合同年度进行的研究。 BRT提供了2份PAC混合物的最终报告，完成了这些研究的报告。 BRT完成了另外3份关于紫锥菊和双酚F免疫毒性研究的报告草案，最终报告将在合同第10年完成。此外，BRT还为6篇稿件提供了领导力、数据分析和写作，其中3篇已被接受在2023财年出版。两份手稿正在国家卫生研究院审批过程中，PAC-MAP研究的几篇论文正在编写中。

The Division of Translation Toxicology (DTT) PAC Mixtures Assessment Program (PAC-MAP) provides the framework for assessing a breadth of individual polycyclic aromatic compounds (PACs), defined PAC mixtures, and complex PAC-containing environmental samples using an in vitro/short-term in vivo testing battery that includes a broad spectrum of endpoints. Select PACs have been associated with a wide range of toxicities (carcinogenicity, immunotoxicity, reproductive and developmental toxicity, neurotoxicity) and a complicated array of mechanisms of action. Many PACs have been associated with suppression of humoral immune function and immunotoxicity has been identified as an informative parameter for estimating the carcinogenic potential of PACs. As part of the potential testing battery to predict mixture effects, we have examined the potential for 13 individual PACs and 3 mixtures to modulate the antigen specific antibody response and affect bone marrow cytology. No in vivo immunotoxicology studies were started in FY23 and efforts were focused on reporting/archiving of studies conducted in previous contract years. BRT provided 2 final reports for PAC Mixtures completing the reporting of those studies. BRT completed an additional 3 draft reports for studies of the Immunotoxicity of Echinacea and Bisphenol F with final reports to be completed in contract year 10. In addition, BRT contributed leadership, data analysis and writing for 6 manuscripts, 3 of which were accepted for publication in FY23. Two manuscripts are in the NIH clearance process and several papers from the PAC-MAP studies are in preparation.