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

评估环境潜力的研究

基本信息

批准号：
10209928
负责人：
FLORENCE BURLESON
金额：
$ 178.88万
依托单位：
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-13 至 2020-08-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10209928
关键词：
Affect Animals Antibody Response Antigens Aromatic Compounds Autoimmune Diseases Biological Assay Bone Marrow Botanicals CTL assay Carbon Nanotubes Chemical Agents Chemicals Chromium Communicable Diseases Complex Contracts Cytology Dermal Development Echinacea purpurea Evaluation Event Exposure to Food Additives Health Health Hazards Hematopoietic Human Hypersensitivity Immunologic Techniques Immunologics Immunosuppression Immunotoxicology In Vitro Individual Measures Methods Molecular National Toxicology Program Neoplasms Pharmaceutical Preparations Predictive Value Pyrenes Reporting Research Resistance Rodent Model Sampling Structure Testing Therapeutic Agents Toxic effect Xenobiotics base carcinogenicity design developmental toxicity dietary supplements environmental agent exposed human population immune function immune system function immunopathology immunoregulation immunotoxicity in vitro testing in vivo in vivo evaluation inorganic phosphate neurotoxicity novel programs reproductive toxicity respiratory response

项目摘要

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. BRT examined 5 chemicals or mixtures for their potential to induce immunotoxicity using rodent models in FY20. These included an extract of the botanical echinacea purpurea, an equimolar PAC mixture, two equipotent PAC mixtures based on the ED10 or ED50 for immune suppression, and a repeat study of the PAC dibenzo(a,l)pyrene, which was first tested in FY19. Final reports were received for immunotoxicology studies on Multiwalled Carbon Nanotubes, Tris (Chloropropyl) phosphate (TCPP), N-Butylbenzenesulfonamide (NBBS), and Echinacea purpurea extract. Two of these studies, NBBS and TCPP, were very large developmental immunotoxicity studies. BRT closed 5 separate immunopathology studies during this fiscal year. BRT provided additional in vivo draft reports to the NTP COR for 4 immunotoxicity studies and 5 immunopathology studies conducted for PAC MAP chemicals which are currently being finalized. Development and evaluation of novel in vitro testing strategies is a major research initiative in the field of immunotoxicology. In FY20, BRT focused their efforts on designing and optimizing a non-radioactive method for replacement of Chromium-51 for direct killing assays. This replacement will provide a safer and effective alternative endpoint for the NK and CTL assays that are integral to the in vivo studies conducted for the NTP under the immunotoxicity testing contract.

PAC 混合物评估计划 (PAC-MAP) 提供了一个框架，用于使用体外/短期体内测试电池（包括广泛的终点）来评估各种单独的多环芳香族化合物 (PAC)、定义的 PAC 混合物以及含 PAC 的复杂环境样品。某些 PAC 与多种毒性（致癌性、免疫毒性、生殖和发育毒性、神经毒性）以及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，并且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，我们研究了单个 PAC 调节抗原特异性抗体反应和影响骨髓细胞学的潜力。 BRT 在 20 财年使用啮齿动物模型检查了 5 种化学品或混合物诱导免疫毒性的潜力。其中包括植物紫锥菊提取物、等摩尔 PAC 混合物、两种基于 ED10 或 ED50 用于免疫抑制的等效 PAC 混合物，以及 PAC 二苯并 (a,l) 芘的重复研究，该研究于 2019 财年首次进行测试。收到了有关多壁碳纳米管、磷酸三（氯丙基）酯 (TCPP)、正丁基苯磺酰胺 (NBBS) 和紫锥菊提取物的免疫毒理学研究的最终报告。其中两项研究，NBBS 和 TCPP，是非常大型的发育免疫毒性研究。 BRT 在本财年完成了 5 项独立的免疫病理学研究。 BRT 向 NTP COR 提供了针对 PAC MAP 化学品进行的 4 项免疫毒性研究和 5 项免疫病理学研究的额外体内草稿报告，目前这些研究正在最终确定。新型体外测试策略的开发和评估是免疫毒理学领域的一项重大研究举措。 2020 财年，BRT 的重点是设计和优化一种非放射性方法，以替代 Chromium-51 进行直接杀灭测定。这种替代将为 NK 和 CTL 测定提供更安全、有效的替代终点，这些测定是根据免疫毒性测试合同为 NTP 进行的体内研究的组成部分。