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

评估环境潜力的研究

• 批准号: 8937071
• 负责人: FLORENCE BURLESON
• 金额: $ 360.56万
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-13 至 2015-08-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8937071
• 关键词: Affect; American; Animals; Antibody Formation; Antigens; Aromatic Compounds; Autoimmune Diseases; Benzo(a)pyrene; Biological Assay; Bone Marrow; Chemical Agents; Chemicals; Coal; Communicable Diseases; Complex Mixtures; Contracts; Cost Savings; County; Cytology; Data; Dermal; Development; Dose; Ethers; Event; Exposure to; Food Additives; Health; Health Hazards; Hematopoietic; Human; Hypersensitivity; Immune system; Immunologic Techniques; Immunotoxicology; In Vitro; Individual; Inhalation Exposure; Intake; Laboratories; Liquid substance; Local Lymph Node Assay; Measures; Methods; Molecular; National Toxicology Program; Neoplasms; Oral; Pharmaceutical Preparations; Phenols; Plants; Predictive Value; Protocols documentation; Research; Resistance; Rivers; Rodent Model; Sampling; Structure; Testing; Therapeutic Agents; Toxic effect; West Virginia; Work; Xenobiotics; carcinogenicity; chemical spill; design; dietary supplements; environmental agent; exposed human population; immune function; immunotoxicity; in vivo; member; multi walled carbon nanotube; neurotoxicity; phenanthrene; programs; propylene; reproductive; respiratory; response; water treatment

This contract was established in the fourth quarter of FY14 and as such, only limited preparatory work has been conducted to date. The protocol for studies to investigate the dose response for irritancy and the sensitizing potential of 4-methylcyclohexylmethanol (MCHM) has been approved by the NTP. MCHM is used as a frothing agent to remove impurities from fine coal. In January, 2014, a chemical storage tank leaked approximately 10,000 gallons of a mixture of Crude MCHM and propylene phenol ethers into the Elk River in West Virginia. The spilled liquid was transported downriver and was withdrawn into the West Virginia American Water treatment plant intake. This water treatment plant serves approximately 300,000 people located in nine counties in southwestern West Virginia. Due to the paucity of data on a number of the chemicals purported to have been spilled, a multi-study project was initiated by NTP to generate data on 8 compounds from the spill, a crude mixture of MCHM and 4 structural class members of the spilled chemicals. The proposed study is a combined Irritancy/Local Lymph Node assay. By combining the two tests in one assay the NTP will reduce the number of animals used to investigate the potential toxicity of the chemicals and realize a cost savings. 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 will examine the potential for individual PACs to modulate the antigen specific antibody response and affect bone marrow cytology. Initial studies will establish dose response curves for the positive control Benzo(a)pyrene and the relatively inactive PAC Phenanthrene. In addition, studies using rodent models to evaluate the potential immunotoxicity of inhalation exposure to multi-walled carbon nanotubes and oral exposure to the groundwater contaminant sulfolane have been designed. Laboratory protocols will be finalized for these studies and the work will be conducted in FY15.

该合同于 2014 财年第四季度签订，因此迄今为止只进行了有限的准备工作。调查 4-甲基环己基甲醇 (MCHM) 刺激性剂量反应和致敏潜力的研究方案已获得 NTP 批准。 MCHM用作泡沫剂，以去除粉煤中的杂质。 2014 年 1 月，一个化学储罐将约 10,000 加仑的粗制 MCHM 和丙烯苯酚醚的混合物泄漏到西弗吉尼亚州的埃尔克河中。溢出的液体被输送到下游并被抽入西弗吉尼亚州美国水处理厂的取水口。该水处理厂为西弗吉尼亚州西南部九个县的约 300,000 人提供服务。由于缺乏有关据称已泄漏的多种化学品的数据，NTP 发起了一项多项研究项目，以生成泄漏中 8 种化合物的数据，这些化合物是 MCHM 和泄漏化学品的 4 种结构类别成员的粗混合物。拟议的研究是刺激性/局部淋巴结联合测定。通过将两种测试结合在一项测定中，NTP 将减少用于研究化学品潜在毒性的动物数量，并实现成本节约。 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，我们将检查单个 PAC 调节抗原特异性抗体反应和影响骨髓细胞学的潜力。初步研究将建立阳性对照苯并(a)芘和相对不活跃的 PAC 菲的剂量反应曲线。此外，还设计了使用啮齿动物模型来评估吸入暴露于多壁碳纳米管和口服暴露于地下水污染物环丁砜的潜在免疫毒性的研究。这些研究的实验室方案将最终确定，工作将于 2015 财年进行。