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Abstract

Grant Number: 1R43ES015641-01
Project Title: Validation of Organotypic Vaginal Tissue Based Assay for Endocrine Disruptors
PI Information:NameEmailTitle
AYEHUNIE, SEYOUM sayehunie@mattek.com SENIOR SCIENTIST

Abstract: DESCRIPTION (provided by applicant): Environmental or intentional 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 develop such a test method. Phase I research will prevalidate MatTek's organotypic vaginal- ectocervical (VEC-FT) tissue model for use in identifying endocrine disruptors (ED). A battery of 25 model compounds with known ED activity will be used. Changes to key hormonal receptors, enzyme activity, tissue structure, proliferation, and gene expression will be monitored. These data will be used to develop a prediction model that will be a sensitive and specific predictor of ED potential. During Phase II, the test method will undergo formal validation in a multi-center, GLP study. The prevalidated in vitro test to be developed for assessing the endocrine disrupting potential of chemicals/ formulations will have enormous environmental and public health significance. Evaluation of endocrine disruptors is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The proposed human organotypic tissue based assay will provide a sensitive and specific assay method to screen a large number of endocrine disrupting chemicals at a reduced cost.

Thesaurus Terms:
cervix, endocrine disrupting compound, environmental toxicology, technology /technique development, toxicant screening, vagina
aromatase, bioassay, cell proliferation, cost effectiveness, enzyme activity, epithelium, estrogen receptor, gene expression, keratinization
human tissue, tissue /cell culture

Institution: MATTEK CORPORATION
200 HOMER AVE
ASHLAND, MA 01721
Fiscal Year: 2007
Department:
Project Start: 01-JUN-2007
Project End: 31-MAY-2008
ICD: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
IRG: ZRG1


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