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混合物评估程序（PAC-MAP）提供了评估单个多环芳族化合物（PAC），定义的PAC混合物以及使用体外/短期内体内测试电池的复杂环境样品的框架。精选的PACS与广泛的毒性（致癌性，免疫毒性，生殖和发育毒性，神经毒性）和复杂的作用机理有关。特别是，许多PAC与抑制体液免疫功能有关，并且已经将免疫毒性确定为估计PAC的致癌潜力的信息参数。作为预测混合物效应的潜在测试电池的一部分，我们检查了单个PAC调节抗原特异性抗体反应并影响骨髓细胞学的潜力。 BRT检查了5种化学物质或混合物，其潜力使用FY20中的啮齿动物模型诱导免疫毒性。其中包括植物性紫锥菊紫癜的提取物，e摩尔PAC混合物，两种基于ED10或ED50的等值PAC混合物，用于免疫抑制，以及对Pac Dibenzo（a，l）pyrene的重复研究，该研究首先在FY19中进行了测试。收到了有关多壁碳纳米管，Tris（氯丙基）磷酸盐（TCPP），N-叔丁基苯甲磺酰胺（NBBS）和棘菊紫罗兰提取物的免疫毒理学研究的最终报告。其中两项研究是NBB和TCPP，是非常大的发育免疫毒性研究。 BRT在这个财政年度关闭了5项单独的免疫病理学研究。 BRT向NTP COR提供了其他体内报告草案，以进行4项免疫毒性研究和5项针对目前正在最终完成的PAC MAP化学物质进行的免疫病理研究。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要研究计划。在第20财年，BRT将精力集中在设计和优化非放射性活性方法上，以替换铬-51进行直接杀害测定。该替换将为NK和CTL分析提供更安全，有效的替代端点，这些NK和CTL测定是在免疫毒性测试合同下针对NTP进行的体内研究所需的组成部分。