ToxSci Advance Access published online on December 14, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl185
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In vitro and In vivo Evaluation of the Estrogenic, Androgenic and Progestagenic Potential of Two Cyclic Siloxanes
Dow Corning Corporation, Midland, Michigan 48686
1 Address correspondence to: Anne L. Quinn, Ph.D., Dow Corning Corporation, 2200 West Salzburg Road, Mail Stop: CO3101, Midland, Michigan 48686-0994, Fax: (989) 496-5595, E-mail: Anne.Quinn{at}dowcorning.com
Received September 13, 2006; accepted November 21, 2006
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The purpose of these experiments was to determine the potential estrogenic, androgenic and progestagenic activity of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5). Receptor binding experiments and a luciferase reporter gene assay were used to determine if the materials were able to bind and activate either the estrogen receptors (ER) or progesterone receptors (PR) -alpha or beta. The rat uterotrophic assay (RUA) for estrogenic activity and the Hershberger assay for androgenic activity were utilized as the in vivo assays. For the estrogen receptor binding studies, D4 was shown to bind to ER-alpha but not to ER-beta. D5 did not bind to either of the two receptors. D4 activated the reporter gene at 10µM while D5 was considered negative in the estrogen reporter gene assay. Neither material was a ligand for the progesterone receptors. Both the RUA and Hershberger assays were conducted using whole body inhalation of the two materials for 16 hours/day. D4 resulted in a small, but significant increase in both wet and blotted uterine weight as well as increases in both luminal and glandular epithelial cell height in both Sprague Dawley and Fischer 344 rats. D5 was negative in both rat strains, indicating that D5 does not possess estrogenic activity. Neither material possessed any significant anti-estrogenic activity. Both materials were negative in the Hershberger assay indicating that neither material possesses any significant androgenic activity. Our studies have shown that D4 exhibits a low affinity for estrogen receptor-alpha in vitro and a weakly estrogenic response in vivo.
Key Words: D4; D5; octamethylcyclotetrasiloxane; decamethylcyclopentasiloxane; silicone; siloxane; estrogen receptor alpha and beta; androgen; progesterone; luciferase reporter gene; RUA; estrogenic.
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