title: An exposure:activity profiling method for interpreting high-throughput screening data for estrogenic activity--proof of concept.
abstract: Rapid high throughput in vitro screening (HTS) assays are now available for characterizing dose-responses in assays that have been selected for their sensitivity in detecting estrogen-related endpoints. For example, EPA's ToxCast™ program recently released endocrine assay results for more than 1800 substances and the interagency Tox21 consortium is in the process of releasing data for approximately 10,000 chemicals. But such activity measurements alone fall short for the purposes of priority setting or screening because the relevant exposure context is not considered. Here, we extend the method of exposure:activity profiling by calculating the exposure:activity ratios (EARs) using human exposure estimates and AC50 values for a range of chemicals tested in a suite of seven estrogenic assays in ToxCast™ and Tox21. To provide additional context, relative estrogenic exposure:activity quotients (REEAQ) were derived by comparing chemical-specific EARs to the EAR of the ubiquitous dietary phytoestrogen, genistein (GEN). Although the activity of a substance in HTS-endocrine assays is not a measure of health hazard or risk, understanding how such a dose compares to human exposures provides a valuable additional metric that can be used in decision-making; substances with small EARs and REEAQs would indicate low priority for further endocrine screening or testing.
authors: American Chemistry Council, 700 2nd St., NE, Washington, DC, United States. Electronic address: rick_becker@americanchemistry.com.
authors: Richard A
authors: RA
authors: Becker
authors: Bayer CropScience LP, Research Triangle Park, NC, United States.
authors: Katie Paul
authors: KP
authors: Friedman
authors: Ted Simon LLC, Winston, GA, United States.
authors: Ted W
authors: TW
authors: Simon
authors: The Dow Chemical Company, Midland, MI, United States.
authors: M Sue
authors: MS
authors: Marty
authors: DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE, United States.
authors: Grace
authors: G
authors: Patlewicz
authors: The Dow Chemical Company, Midland, MI, United States.
authors: J Craig
authors: JC
authors: Rowlands
mesh_terms: D003661:Decision Support Techniques; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D019833:Genistein / Q000633:toxicity; D057166:High-Throughput Screening Assays / Q000592:standards; D006801:Humans; D048789:Phytoestrogens / Q000633:toxicity; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D015203:Reproducibility of Results; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D052244:Endocrine Disruptors; D004967:Estrogens; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D019833:Genistein
keywords: Endocrine disruption; Estrogen assays; Exposure; Exposure:activity ratio; Genistein; Potency; Relative estrogenic exposure:activity quotient; Tox21; ToxCast™