ICCVAM recommended reference chemicals for validation of in vitro estrogen and androgen receptor binding and transcriptional activation assays

BC Blackard¹, CJ Inhof¹, RR Tice¹, WS Stokes², M Wind³, D Hattan⁴, LM Schechtman⁴

1. Integrated Laboratory System, Inc./NICEATM, RTP, NC, USA
2. NICEATM/NIEHS, RTP, NC, USA
3. U.S. Consumer Product Safety Commission, Bethesda, MD, USA
4. U.S. Food and Drug Administration, Rockville, MD, USA

In 1998, the U.S. EPA's Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) recommended the standardization and validation of several assays for identifying possible endocrine-disrupting (ED) substances. Included among these assays are estrogen (ER) and androgen receptor (AR) binding and/or transcriptional activation (TA) assays. NICEATM and the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) convened an independent scientific expert panel to evaluate the status of these assays and proposed reference chemicals for validation studies. Based on the expert panel's recommendations and public comments on a draft list of substances, ICCVAM prepared a final list of 78 substances for use in future ER/AR binding/TA validation studies. ICCVAM recommends testing a minimum of 53 substances for ER-based assays and 44 substances for AR-based assays; each set includes at least 25% negative or presumed negative substances. The use of this standard list of reference substances in future validation studies will facilitate determination of the acceptability of in vitro and in vivo assays and test batteries for inclusion in screening programs for ED substances. However, to comprehensively assess the usefulness of ER/AR binding/TA assays as individual components of the EDSTAC Tier 1 screening battery, and to facilitate development of more predictive in vitro ED assays, ICCVAM recommends that all 78 substances be tested in the four types of assays. This will generate a high quality in vitro database to facilitate future validation efforts and comparison of performance among different test methods and protocols. ILS staff supported by NIEHS Contract N01-ES 35504.

P091

Date: Tuesday, August 23, 2005, 13.00-14.00 h

5.1 Session: Strategies for Using Non-animal Methods in Relation to HPV, Endocrine Disruptors, and REACH Legislation.