CORE--Synthesis

核心--综合

• 批准号: 7466429
• 负责人: Hans J Lehmler
• 金额: $ 19.4万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7466429
• 关键词: Aroclor 1254; Calibration; Chicago; Collaborations; Glutathione; In Vitro; Individual; Inhalation Toxicology; Inorganic Sulfates; Iowa; Polychlorinated Biphenyls; Preparation; Quality Control; Reference Standards; Research; Research Project Grants; Research Support; Signal Transduction; Solutions; Standards of Weights and Measures; Sulfur; Support of Research; Testing; Universities; Unspecified or Sulfate Ion Sulfates; Work; aroclor 1242; experience; in vivo; interest; programs

The Synthesis Core directly supports the research function of the University of Iowa SBRP research program by providing a PCB exposure mixture as well as individual PCB congeners and PCB metabolites. In support of the Analytical Core, this core will also provide analytical standards. Specific Aim 1 is the preparation of analytical and quality control/assurance standards for the Analytical Core. In close collaboration with the Analytical Core, which is responsible for purity control of PCB congeners and testing of prepared standards against certified Standard Reference Materials, the Synthesis Core will acquire or synthesize individual PCB congeners and prepare stock solutions for use as PCB calibration mixtures. Specific Aim 2 is the preparation of an airborne PCB exposure mixture for in vitro and in vivo studies for Research Projects #1, #2, #3, and # 5. This exposure mixture will approximate the PCB congener profile of the mean Chicago PCB signal. The mixture will be prepared in close cooperation with the Analytical and Inhalation Toxicology Cores by mixing of Aroclor 1242, Aroclor 1254 and individual PCB congeners. Specific Aim 3 is the synthesis of PCB congeners to supplement the PCB exposure mixture in Aim 2 and for use with the in vitro and in vivo studies of Research Projects #1, #2, #3, and # 5. These PCB congeners will also be available to the Analytical Core for the preparation of analytical and quality control/assurance standards. Specific Aim 4 is the synthesis of methoxylated and hydroxylated PCB metabolites. Hydroxylated PCB metabolites will be used by Projects #1, #2, #3, and #5 for in vitro and in vivo studies. Both the hydroxylated and methoxylated PCB derivatives will be provided to the Analytical Core and individual research projects as analytical standards for the identification and quantification of (unknown) metabolites. Specific Aim 5 is the synthesis of quinoid metabolites of PCBs and their glutathione conjugates for Research Projects #1 and #2. Specific Aim 6 will provide PCB sulfates needed by Project #3. All compounds will be synthesized, if necessary in large (gram) quantities, with straightforward synthetic approaches that are well established at the University of Iowa. Drawing on their extensive experience with the synthesis of organohalogen compounds, Synthesis Core staff will be able to synthesize every compound of interest to the individual research projects.

综合核心直接支持爱荷华大学SBRP研究计划的研究职能 通过提供多氯联苯暴露混合物以及单独的多氯联苯同系物和多氯联苯代谢物。在支持中 在分析核心中，该核心还将提供分析标准。具体目标1是准备 分析核心的分析和质量控制/保证标准。与……密切合作 分析核心，负责多氯联苯同系物的纯度控制和已制备的 标准对照认证的标准参考物质，合成核心将获得或合成 独立的多氯联苯同系物，并准备用作多氯联苯校准混合物的库存溶液。具体目标2 是用于体外和体内研究的气载多氯联苯暴露混合物的制备 项目#1、#2、#3和#5。这种暴露混合物将近似平均 芝加哥印刷电路板信号。混合物的制备将与分析和吸入法密切合作 由Aroclor 1242、Aroclor 1254和单独的多氯联苯同系物混合而成的毒理核心。具体目标3是 合成多氯联苯同系物以补充目标2中的多氯联苯暴露混合物并用于 研究项目#1、#2、#3和#5的体外和体内研究。这些多氯联苯的同系物也将 提供给分析核心，以编制分析和质量控制/保证标准。 具体目标4是合成甲氧基化和羟基化的多氯联苯代谢物。羟化印制电路板 代谢物将被项目#1、#2、#3和#5用于体外和体内研究。两者都是羟基化的 和甲氧基化的多氯联苯衍生物将提供给分析核心和个别研究项目 (未知)代谢物鉴定和定量的分析标准。具体目标5是 多氯联苯及其谷胱甘肽结合物的喹类代谢物的合成研究项目1 和#2.具体目标6将提供项目3所需的多氯联苯硫酸盐。所有化合物都将 合成，如果需要，大量(克)，用直接的合成方法，很好 成立于爱荷华大学。利用他们在合成方面的丰富经验 有机卤素化合物，合成核心员工将能够合成每一种感兴趣的化合物 个人研究项目。