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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：
10023392
负责人：
FLORENCE BURLESON
金额：
$ 148.21万
依托单位：
BRT-BURLESON RESEARCH TECHNOLOGIES, INC.
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/10023392
关键词：
Adult Affect Animals Antibody Response Antigens Aromatic Compounds Autoimmune Diseases Bone Marrow Carbon Nanotubes Chemical Agents Chemicals Chrysenes Communicable Diseases Complex Contracts Cytology Dermal Development Event Exposure to Flame Retardants Food Additives Health Health Hazards Hematopoietic Human Hypersensitivity Immunologic Techniques Immunologics Immunotoxicology In Vitro Individual Inhalation Exposure Measures Methods Molecular Mus National Toxicology Program Neoplasms Oral Pharmaceutical Preparations Plasticizers Predictive Value Pyrenes Rattus Reporting Research Resistance Sampling Sodium Structure Testing Therapeutic Agents Toxic effect Xenobiotics carcinogenicity developmental toxicity dietary supplements environmental agent exposed human population immune function immune system function immunoregulation immunotoxicity in vivo in vivo evaluation inorganic phosphate neurotoxicity 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. 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.

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。两项 PAC-MAP 研究的最终报告于 2019 财年收到。另外三种化合物（二苯并噻吩、屈、二苯并(a,l)芘）的报告草稿已由 NTP 审核，预计将于 20 财年第一季度完成。评估特定 PAC 混合物的研究于 2019 财年第四季度开始。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，口服暴露于偏钒酸钠和 NTP 报告正在进行中。关于阻燃剂磷酸三（氯丙基）酯和增塑剂正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。