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

PAC混合物评估计划(PAC-MAP)提供了使用包括广泛终点的体外/短期体内测试电池评估单个多环芳烃(PAC)、已定义的PAC混合物和含有PAC的复杂环境样品的框架。部分PAC与广泛的毒性(致癌、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有关。特别是，许多PAC与体液免疫功能的抑制有关，免疫毒性已被确定为评估PAC致癌潜力的信息参数。作为预测混合效应的潜在测试电池的一部分，我们研究了单个PAC调节抗原特异性抗体反应并影响骨髓细胞学的可能性。19财年收到了两份PAC-MAP研究的最终报告。NTP已经审查了另外三种化合物--二苯并噻吩类、大黄烯类、二苯并(a，L)芘的报告草案，预计将于20财年第一季度完成。对已确定的PAC混合物进行评估的研究始于19年第四季度。已收到评估吸入多壁碳纳米管对成年小鼠和大鼠的潜在全身免疫毒性的最终报告，口服偏钒酸钠和NTP的报告正在进行中。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已经完成，这些研究的报告正在审查中。

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.