National Toxicology Program

The MCF-7 Cell Proliferation Assay of Estrogenic Activity measures whether, and to what extent, a substance induces cell proliferation via estrogen receptor (ER)-mediated pathways. The assay uses MCF-7 cells, an immortalized human breast adenocarcinoma cell line that endogenously expresses ER.

The assay was developed and refined by CertiChem Inc., in collaboration with laboratories at the University of Missouri and Northwestern University. A background review document (BRD) was prepared describing the historical development and rationale for the assay, and results from testing done at all three facilities were presented in support of the assay.

In accordance with the ICCVAM nomination process, a pre-screen evaluation of the CertiChem Inc. BRD was conducted to determine the extent to which:

• The BRD addressed ICCVAM prioritization criteria
• The BRD provided the information requested in the ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods (NIH Pub. No. 03-4508)
• The proposed test method adheres to the recommendations of the Background Review Document (BRD): ICCVAM Evaluation of In Vitro Test Methods for Detecting Potential Endocrine Disruptors (NIH Pub. No. 03-4503), especially those regarding essential test method components
• The proposed test method showed adequate performance (reliability and accuracy) during pre-validation to warrant consideration for validation studies

The pre-screen evaluation was made available to the public and ICCVAM invited comments on whether the CertiChem Inc. MCF-7 Cell Proliferation Assay of Estrogenic Activity should be considered for additional validation studies. Public comments and recommendations from the Scientific Advisory Committee on Alternative Toxicological Methods were considered and ICCVAM has recommended that the assay be given a high priority for additional validation.