Validation of Human Vaginal Tissue Assay for Endocrine Disruptors

人体阴道组织内分泌干扰物检测的验证

• 批准号: 8057227
• 负责人: Seyoum Ayehunie
• 金额: $ 32.78万
• 依托单位: MATTEK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8057227
• 关键词: Adverse effects; Advisory Committees; Affect; Agonist; Agriculture; Androgens; Animal Testing; Animals; Area; Biological Assay; Biological Markers; Blinded; Cell Culture Techniques; Cells; Chemical Agents; Chemical Exposure; Chemicals; Development; Dose; Drug Industry; Economics; Endocrine; Endocrine Disruptors; Endocrine disruption; Endocrine system; Environmental Exposure; Environmental Health; Environmental Pollution; Estrogen Receptors; Estrogens; Estrone; Evaluation; Exposure to; Fetal Development; Food Processing; Gene Expression; Hazard Identification; Health; Histology; Hormone Receptor; Hormones; Human; Immune system; In Vitro; Interagency Coordinating Committee on the Validation of Alternative Methods; Laboratories; Malignant Neoplasms; Methods; Modeling; Monitor; Morphology; Occupational Exposure; Phase; Production; Public Health; Reproducibility; Reproductive system; Research; Research Project Grants; Rodent; Safety; Screening procedure; Structure; System; Testing; Thyroid Gland; Tissue Model; Tissues; United States Environmental Protection Agency; Vagina; Validation; Women' s Health; base; carcinogenesis; cost; environmental chemical; hazard; high throughput screening; hormone regulation; human tissue; in vitro Assay; operation; progesterone receptor B; programs; reproductive; response; validation studies

DESCRIPTION (provided by applicant): Environmental or occupational exposure to a broad variety of chemical agents can alter normal endocrine function. The effects of these "endocrine disruptors" (ED) can have serious health implications including deleterious effects to reproductive capacity, fetal development, the immune system, and carcinogenesis. Current animal tests are expensive, use a large number of animals, and are not necessarily applicable to humans. Thus, a validated, human in vitro method to identify ED is an area of great importance. This research project will validate an organotypic EpiVaginal tissue model for Tier 1 screening of chemicals with endocrine disrupting potential. Phase I research will validate MatTek's organotypic vaginal-ectocervical (EpiVaginalTM) tissue model for use in identifying ED. A battery of 75 model compounds with known ED activity will be selected from the revised ICCVAM list of recommended substances. The production of estrone by the tissue model and changes to tissue morphology and gene expression will be monitored as biomarkers of ED. A prediction model for ED with be finalized and the test method will undergo formal validation in a multi-center, GLP study. In addition, reproducibility of the assay method and adaptation of the method to a high throughput screen format will be investigated. If successful, the proposed method will have high impact in environmental chemical safety programs and ultimately will reduce the effect of these chemicals on human health. PUBLIC HEALTH RELEVANCE: Validation an in vitro organotypic tissue based assay to screen for endocrine disrupting potential is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The assay method will be adapted to a high throughput format to allow rapid and low- cost screening of chemicals. The organotypic tissue based in vitro screening method will have enormous environmental and public health significance.

描述(由申请人提供)：环境或职业暴露于多种化学制剂会改变正常的内分泌功能。这些“内分泌干扰物”(ED)的影响可能会对健康产生严重影响，包括对生殖能力、胎儿发育、免疫系统和致癌的有害影响。目前的动物试验费用昂贵，使用大量动物，而且不一定适用于人类。因此，一种有效的、人类体外鉴定ED的方法是一个非常重要的领域。这项研究项目将验证器官型表观阴道组织模型，用于一级筛选具有内分泌干扰潜力的化学物质。第一阶段研究将验证Mattek的器官型阴道-宫颈外(EpiVaginalTM)组织模型用于识别ED。已知ED活性的75种模型化合物将从修订的ICCVAM推荐物质清单中选出。通过组织模型产生雌酮以及组织形态和基因表达的变化将被监测为ED的生物标志物。勃起功能障碍的预测模型已经敲定，测试方法将在一项多中心的GLP研究中进行正式验证。此外，还将研究该分析方法的重复性以及该方法对高通量屏幕格式的适应性。如果成功，建议的方法将对环境化学安全计划产生很大影响，最终将减少这些化学物质对人类健康的影响。 公共卫生相关性：验证基于器官组织的体外分析以筛选内分泌干扰潜力，对于将对人类和野生动物暴露在干扰正常荷尔蒙调节的化学品中的危害降至最低非常重要。化验方法将适用于高通量格式，以实现对化学品的快速和低成本筛选。基于器官类型组织的体外筛选方法将具有巨大的环境和公共卫生意义。