Support of the Research Effort to Evaluate the Cardiotoxic Potential of Multiple Test Agents in Rats

支持评估多种测试药物对大鼠的心脏毒性潜力的研究工作

• 批准号: 10710449
• 负责人: MILTON HEJTMANCIK
• 金额: $ 23.33万
• 依托单位: BATTELLE MEMORIAL INSTITU
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2023-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710449
• 关键词: Cardiotoxicity; Chemicals; Data; Dose; Evaluation; Heart; Histopathology; Human; In Vitro; Literature; Monitor; Oral; Publishing; Rattus; Research Support; Testing; Toxic effect; Toxicology; Translations; animal data; base; design; in vitro testing; in vivo; transcriptomics

This project conducted for the Division of Translational Toxicology (DTT) is designed to develop and qualify a toxicity evaluation pipeline for test agents with cardiotoxic potential. A suite of 9-10 chemicals were selected based on demonstrating the ability to be cardiotoxic from published literature of mechanistic, in vitro or in vivo studies. These chemicals are being tested in a 14-day repeat oral gavage study in rats with an emphasis on evaluation of the heart using histopathology and transcriptomics, as well as internal dose monitoring to provide translational data for animal to human and in vitro to in vivo extrapolation.

该项目为转化毒理学部门（DTT）进行，旨在开发和鉴定具有心脏毒性潜力的测试剂的毒性评估管道。根据已发表的机械、体外或体内研究文献中显示的心脏毒性，选择了一组9-10种化学物质。这些化学物质正在对大鼠进行为期14天的重复口服灌胃研究，重点是利用组织病理学和转录组学评估心脏，以及内部剂量监测，为动物到人类和体外到体内的外推提供转化数据。