In Vitro and In Vivo Evaluation of the Estrogenic, Androgenic, and Progestagenic Potential of Two Cyclic Siloxanes

Abstract

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 (ERs) or progesterone receptors (PRs)-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 ER-binding studies, D4 was shown to bind to ERalpha but not to ERbeta. D5 did not bind to either of the two receptors. D4 activated the reporter gene at 10 microM, while D5 was considered negative in the estrogen reporter gene assay. Neither material was a ligand for the PRs. Both the RUA and Hershberger assays were conducted using whole-body inhalation of the two materials for 16 h/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 antiestrogenic 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 ERalpha in vitro and a weakly estrogenic response in vivo.

Understanding the effects of the origin, occurrence, monitoring, control, fate and removal of siloxanes on the energetic valorization of sewage biogas—A review

“…Significant gaseous exchange via the lungs is predicted in air breathing organisms [42], suggesting that c-VMS may not bioaccumulate in birds, cetaceans and pinnipeds. Moreover, in vitro exposure to D4 via injection in mice caused fatal liver and lung damage [43], oral exposure to D4 caused oestrogenic effects [44][45][46] and inhalation of D5 affected the nervous system [47]. In the case of human beings, although in short-term and controlled studies no immunologic or pro-inflammatory effects of D4 were observed, the European Union suggested some damaging effects on hormone function that may result in infertility [48].…”

Cosmetics use and age at menopause: is there a connection?

“…One study looked at use of personal care products in a cohort of 94 postmenopausal women in Norway and serum levels of estrogenic (20) and anti-androgenic (21) cyclic volatile methylsiloxanes (cVMS) (22). Sources of exposure to cVMS are generally through cVMS present in personal care products, inhalation due to the volatility of the compounds, or cVMS contained in breast implants (22).…”

Distribution, Elimination, and Rearrangement of Cyclic Volatile Methylsiloxanes in Oil-Contaminated Soil of the Shengli Oilfield, China

“…In a recent peer-reviewed paper, Quinn et al (2007) used receptor-binding experiments and a luciferase reporter gene assay to determine if D5 was able to bind and activate either the estrogen receptors (ERs) or the progesterone receptors (PRs). They used the rat uterotrophic assay (RUA) for estrogenic activity and the Hershberger assay for androgenic activity as in vivo assays.…”