BG1Luc ER TA Test Method: Results of an International Validation Study and Proposed Performance Standards

the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has completed its evaluation of the validation status of the lUMI-Cell BG1luc4e2 eR tA test method (hereafter, BG1luc eR tA test method) as a screening test to identify substances with in vitro estrogen receptor agonist and antagonist activity. A test method evaluation report has been published (ICCVAM, 2011a), providing ICCVAM’s recommendations for the BG1luc eR tA test method based on the results of an international validation study and the demonstrated validity (usefulness and limitations). the report includes (1) protocols recommended by ICCVAM for future data collection and evaluation for the BG1luc eR tA test method, (2) a background review document (BRD) describing the validation status of this test method, (3) recommendations for future studies, and (4) performance standards to evaluate functionally and mechanistically similar test methods. xenobiotics Detection Systems, Inc. (xDS, Durham, NC) nominated the BG1luc eR tA test method to ICCVAM for an interlaboratory validation study. this test method uses BG1 cells (a human ovarian carcinoma cell line) that are stably transfected with an estrogen-responsive luciferase reporter gene to measure whether and to what extent a substance induces or inhibits tA activity via eR mediated pathways. ICCVAM and the Scientific Advisory Committee on Alternative Toxicological Methods (SACAtM) recommended that the BG1luc eR tA should be considered a high priority for interlaboratory validation studies, given the lack of adequately validated test methods and the regulatory and public health need for such test methods. the National toxicology Program Interagency Center for the evaluation of Alternative toxicological Methods (NICeAtM) subsequently led and coordinated an international validation study with its counterparts in europe (the european Centre for the Validation of Alternative Methods) and Japan (the Japanese Center for the evaluation of Alternative Methods) to assess the accuracy and reliability of the BG1luc eR tA test method for the qualitative detection of substances with in vitro eR agonist or antagonist activity. Following completion of this study, NICeAtM, ICCVAM, and the ICCVAM endocrine Disruptor Working Group (eDWG) prepared a draft BRD and draft test method recommendations. the drafts were provided to an independent international scientific peer review panel (hereafter Panel) and to the public for comment. the Panel met in public session on March 29-30, 2011 to discuss its peer review of the ICCVAM draft BRD and to provide conclusions and recommendations regarding the validation status of the BG1luc eR tA test method. the Panel also reviewed how well the information contained in the draft BRDs supported ICCVAM’s draft test method recommendations (ICCVAM, 2011b). In finalizing this test method evaluation report and the BRD, ICCVAM considered the conclusions and recommendations of the Panel, comments from ICCVAM’s Scientific Advisory Committee on Alternative toxicological Methods (SACAtM), and public comments. BG1Luc ER TA Test Method: Results of an International Validation Study and Proposed Performance Standards Warren Casey 1, Patricia Ceger 2, Dave Allen 2, Judy Strickland 2, Jon Hamm 2, Mike Paris 2, and William Stokes1 1NtP Interagency Center for the evaluation of Alternative toxicological Methods, National Institute of environmental Health Sciences, Research triangle Park, NC, USA; 2IlS Incorporated, Research triangle Park, NC, USA