Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products.
Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The "active" ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions.
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Huixiao.Hong@fda.hhs.gov.
Huixiao
H
Hong
Division of Nonprescription Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Diego.Rua@fda.hhs.gov.
Diego
D
Rua
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Suguna.Sakkiah@fda.hhs.gov.
Sugunadevi
S
Sakkiah
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Selvaraj.Chandrabose@fda.hhs.gov.
Chandrabose
C
Selvaraj
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Weigong.Ge@fda.hhs.gov.
Weigong
W
Ge
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Weida.Tong@fda.hhs.gov.
Weida
W
Tong
estrogenic activity; ingredient; model; prediction; sunscreen
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