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

PAC混合物评估计划（PAC-MAP）提供了一个框架，用于评估单个多环芳香族化合物（PAC），定义的PAC混合物和复杂的PAC含有环境样品的广度，使用体外/短期体内测试电池，包括广泛的端点。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。特别是，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。作为预测混合效应的潜在测试组合的一部分，我们检查了单个PAC调节抗原特异性抗体应答和影响骨髓细胞学的潜力。 2019财年收到了两项PAC-MAP研究的最终报告。NTP已经审查了另外三种化合物（二苯并噻吩、二苯并（a，l）芘）的报告草案，预计将在2020财年第一季度完成。 评估PAC混合物的研究始于2019财年第4季度。 已收到成年小鼠和大鼠吸入暴露于多壁碳纳米管后潜在全身免疫毒性评估的最终报告，经口暴露于偏钒酸钠和NTP报告正在进行中。已经完成了对阻燃剂磷酸三（氯丙基）酯和增塑剂N-丁基苯磺酰胺的发育免疫毒理学研究，正在审查这些研究的报告。

The 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. In particular, 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 individual PACs to modulate the antigen specific antibody response and affect bone marrow cytology. Final reports for two PAC-MAP studies, were received in FY19. Draft reports for three additional compounds, dibenzothiophene, chrysene, dibenzo(a,l)pyrene have been reviewed by the NTP and are expected to close in Q1FY20. Studies evaluating defined mixtures of PACs began in Q4FY19. Final reports have been received for the assessment of the potential systemic immunotoxicity following inhalation exposure to multiwalled carbon nanotubes in adult mice and rats, and oral exposure to sodium metavandate and NTP reporting is in progress. Developmental immunotoxicology studies on the flame retardant Tris(Chloropropyl) phosphate and the plasticizer N-Butylbenzenesulfonamide have been completed and the reports for these studies are under review.