An In Vitro Robotic Assay for Anti-Estrogenic Activity

抗雌激素活性的体外机器人测定

• 批准号: 7676901
• 负责人: Cathy Z Yang
• 金额: $ 7.53万
• 依托单位: CERTICHEM, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7676901
• 关键词: Adverse effects; Animal Feed; Antioxidants; Behavioral; Biological Assay; Cell Proliferation; Chemicals; Cosmetics; Data; Development; Diet; Endocrine; Endocrine Disruptors; Environment; Estrogens; Evaluation; Feasibility Studies; Food; Food Additives; Food Preservatives; Funding; Genes; Goals; Grant; Health; High Pressure Liquid Chromatography; Hormones; Human; In Vitro; Investigation; Knowledge; MCF7 cell; Mammals; Measures; Methods; Mission; National Toxicology Program; Numbers; One-Step dentin bonding system; Paper; Pesticides; Pharmacologic Substance; Phase; Physiological Processes; Plastics; Polymers; Prevalence; Reporting; Reproducibility; Robotics; Sampling; Scientist; Screening procedure; Silicones; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Testing; Time; Transcriptional Activation; United States Environmental Protection Agency; United States Food and Drug Administration; United States National Institutes of Health; Validation; Work; Writing; chemical release; commercial application; commercialization; consumer product; cost effective; design; desire; estrogenic activity; experience; fetal; in vivo; monomer; reproductive; social

DESCRIPTION (provided by applicant): Recent scientific investigations have shown that many chemicals used in plastics, pharmaceuticals, pesticides, cosmetics, food additives, etc., are endocrine disruptors (EDs). EDs interfere in various ways with hormones such as estrogens to have significant adverse effects on many behavioral and physiological processes. ED effects (e.g. estrogenic or anti-estrogenic) sometimes occur at very low (picomolar to nanomolar) concentrations, especially on fetal or developing mammals (including humans). The prevalence and actions of EDs in our environment warrant the development of valid assay methods. Consequently, various governmental bodies (e.g., EPA, FDA, and ICCVAM) and proactive corporations have explicitly expressed a desire to have in vitro robotic assays for EDs, such as anti-estrogenic activity (anti-EA). However, no robotic anti-EA assay is commercially available. To begin to meet these governmental, scientific and commercial needs, CertiChem (CCi) has completed a Phase I SBIR grant showing that it is feasible to develop an anti- EA robotic assay that would be valid (i.e., reliable, accurate, versatile, rapid, and cost effective) using MCF-7 cells. In this Phase II application, CCi now proposes to develop this robotic assay for anti-EA for commercialization by repeatedly assaying a set of 78 reference test chemicals to confirm the reliability and accuracy of CCi's proposed anti- EA assay. CCi also proposes to demonstrate the versatility of this assay by examining the anti-EA in a set of antioxidants used in foodstuffs and plastics. Finally, CCi proposes to perform HPLC separation assays on some reference test chemicals to confirm that their anti-EA is not due to contamination and to enhance the versatility of this assay for commercial use. Development of a robotic screening assay for anti-EA is commercially, scientifically, and socially important because of the large number of chemicals (>10,000) - much less chemical mixtures - that should now be screened for anti-EA by profit, non-profit, or governmental entities. Development of a robotic assay for anti-EA is desired as part of the mission of NIEHS, EPA and ICCVAM. Recent scientific investigations have shown that many (perhaps over 10,000) chemicals used in common products such as plastics, pesticides, cosmetics, and food additives have estrogenic/anti-estrogenic activities that severely interfere with normal estrogen actions to produce adverse effects on many behavioral, reproductive, and physiological processes in humans. In this Phase II proposal, CertiChem (CCi) proposes to develop a very sensitive and accurate assay to measure anti-estrogenic activity in a set of reference test chemicals and in common consumer products. CCi proposes to use these data and CCi's data on estrogenic activity on many chemicals to identify which chemicals have anti-estrogenic activity and to work with various firms to design consumer products that are free of chemicals that release anti-estrogenic or estrogenic activities.

描述（由申请人提供）：最近的科学研究表明，塑料、药品、农药、化妆品、食品添加剂等中使用的许多化学品都是内分泌干扰物（EDs）。ed通过多种方式干扰雌激素等激素，对许多行为和生理过程产生显著的不良影响。ED效应（如雌激素或抗雌激素）有时发生在非常低的浓度（皮摩尔到纳摩尔），特别是对胎儿或发育中的哺乳动物（包括人类）。环境中EDs的普遍存在和作用要求开发有效的检测方法。因此，各种政府机构（如EPA、FDA和ICCVAM）和积极进取的公司都明确表示希望对ed进行体外机器人检测，如抗雌激素活性（anti-EA）。然而，目前还没有商业上可用的机器人抗ea检测。为了开始满足这些政府，科学和商业需求，CertiChem （CCi）已经完成了I期SBIR授权，表明使用MCF-7细胞开发一种有效（即可靠，准确，通用，快速和经济有效）的反EA机器人检测是可行的。在这个II期申请中，CCi现在提议通过重复分析一组78个参考测试化学品来开发这种抗EA机器人检测方法，以确认CCi提出的抗EA检测方法的可靠性和准确性。CCi还建议通过检查食品和塑料中使用的一组抗氧化剂中的抗ea来证明该测定法的多功能性。最后，CCi建议对一些参考测试化学品进行HPLC分离分析，以确认其抗ea不是由于污染，并增强该分析的商业用途的通用性。机器人抗ea筛选试验的发展具有商业、科学和社会重要性，因为大量的化学物质（100万）-更少的化学混合物-现在应该由利润、非营利或政府实体筛选抗ea。作为NIEHS， EPA和ICCVAM任务的一部分，需要开发抗ea的机器人检测。最近的科学研究表明，塑料、杀虫剂、化妆品和食品添加剂等常用产品中使用的许多（可能超过10,000种）化学物质具有雌激素/抗雌激素活性，严重干扰正常的雌激素作用，对人类的许多行为、生殖和生理过程产生不利影响。在这个II期提案中，CertiChem （CCi）提议开发一种非常敏感和准确的检测方法来测量一组参考测试化学品和普通消费品中的抗雌激素活性。CCi建议使用这些数据以及CCi关于许多化学物质的雌激素活性的数据来确定哪些化学物质具有抗雌激素活性并与不同的公司合作设计不含释放抗雌激素或雌激素活性的化学物质的消费品。