VALIDATION OF AN IN VITRO ASSAY FOR ANDROGENIC ACTIVITY

DESCRIPTION provided by applicant Recent scientific investigations have shown that many chemicals used in plastics pharmaceuticals pesticides cosmetics food additives etc are endocrine disrupting chemicals EDCs EDCs interfere in various ways with hormones such as estrogens and androgens and can have significant adverse effects on many behavioral and physiological processes ED effects agonistic or antagonistic sometimes occur at very low picomolar to nanomolar concentrations especially in fetal or developing mammals including humans The prevalence and actions of EDCs in our environment warrant the development of valid testing 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 EDCs such as for androgenic AnA or anti androgenic Anti AnA activity However no reliable manual or robotic AnA or Anti AnA assays are yet commercially available ICCVAM NICEATM desire single laboratory validation assays of AnA and Anti AnA using a human based cell line To begin to meet these governmental scientific and commercial needs CertiChem CCi is submitting a Fast Track grant to show that it is feasible to develop AnA and Anti AnA assays in manual and medium throughput robotic formats that would be reliable accurate versatile rapid and cost effective CCi proposes to use MDA kb human based cells In our AnA and anti AnA assays these cells will be examined by a transcription reporter gene luciferase assay CCi proposes to examine Test Substances supplied and coded by ICCVAM for AnA and Anti AnA validation to confirm that CCiandapos s assays can accurately assess their AR agonistic and antagonistic activities CCi also proposes to test hydrophilic and hydrophobic extracts of silicone and paper products for AnA and Anti AnA Development of manual and robotic screening assays for AnA and anti AnA is highly desired as part of the mission of NIEHS EPA and ICCVAM as commercially scientificly and socially important Government agencies are now screening a large number of chemicals for hormonal activity including AR agonist and antagonist activities In addition hormonal activity of chemical mixtures extracted from commercial products is of great importance to government agencies NGOs and consumers PUBLIC HEALTH RELEVANCE Recent scientific investigations have shown that many chemicals used in common products such as plastics pesticides cosmetics and food additives have Androgenic and or Anti Androgenic male hormone activity that could potentially interfere with normal androgen actions to produce adverse effects on many behavioral reproductive and physiological processes in humans In this Fast Track SBIR application CertiChem CCi proposes a single lab validation of the MDA kb assays by repeatedly testing Test Substances coded and supplied by ICCVAM an intergovernmental agency that validates in vitro assays to show that our AR agonist and antagonist assays in MDA kb cells are both reliable and accurate Afterward CertiChem will use this assay to test high commercial value consumer products made with silicone or paper