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: 8418779
• 负责人: Seyoum Ayehunie
• 金额: $ 18.9万
• 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/8418779
• 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; 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; public health relevance; reproductive; response; screening; 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.

描述（由申请人提供）：环境或职业暴露于各种化学制剂可改变正常的内分泌功能。这些“内分泌干扰物”（艾德）的影响可能对健康产生严重影响，包括对生殖能力、胎儿发育、免疫系统和致癌作用的有害影响。目前的动物试验价格昂贵，使用大量动物，不一定适用于人类。因此，鉴定艾德的经验证的人体外方法是非常重要的领域。该研究项目将验证一种器官型EpiVaginal组织模型，用于对具有内分泌干扰潜力的化学品进行一级筛选。 I期研究将验证MatTek的器官型阴道-宫颈外（EpiVaginalTM）组织模型用于识别ED。将从修订后的ICCVAM推荐物质清单中选择75种具有已知艾德活性的模型化合物。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作为ED的生物标志物进行监测。艾德的预测模型将最终确定，测试方法将在多中心GLP研究中进行正式验证。此外，还将研究测定方法的重现性和该方法对高通量筛选格式的适应性。如果成功，所提出的方法将对环境化学品安全计划产生重大影响，并最终减少这些化学品对人类健康的影响。