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

基本信息

批准号：
8207929
负责人：
Seyoum Ayehunie
金额：
$ 46.08万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
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/8207929
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&apos 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 validation studies

项目摘要

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.