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Octamethylcyclotetrasiloxane exhibits estrogenic activity in mice via ERalpha.

Authors
He-B; Rhodes-Brower-S; Miller-MR; Munson-AE; Germolec-DR; Walker-VR; Korach-KS; Meade-BJ
Source
Toxicol Appl Pharmacol 2003 Nov; 192(3):254-261
NIOSHTIC No.
20032133
Abstract
Octamethylcyclotetrasiloxane (D4) is a low molecular weight cyclic silicone used in the synthesis of larger silicone polymers and in the formulation of a variety of personal care products. The effects of oral D4 exposure in mice on serum estradiol levels, uterine wet weight, and uterine peroxidase activity were investigated. Additionally, in vitro estrogen receptor binding activity was evaluated. Serum estradiol levels decreased in a dose-dependent manner after exposure to 100 mg/kg to 1000 mg/kg D4. Studies with adrenalectomized animals demonstrated that the decreased serum estradiol levels were not due to elevated serum corticosterone levels. Uterine wet weights in ovariectomized mice were significantly increased in a dose-dependent manner by exposure to 250-1000 mg of D4/kg, but not by exposure to other silicone compounds tested (hexamethylcyclotrisiloxane, decamethylcyclopentasiloxane, decamethyltetrasiloxane, and octaphenylcyclotetrasiloxane). Uterine peroxidase activity, a marker for estrogenic activity, was also significantly increased in D4-exposed mice, but not in mice exposed to the other siloxanes. Pretreating mice with the estrogen receptor antagonist ICI 182,780 completely blocked the D4-induced increase in uterine weight, and ovariectomized estrogen receptor-alpha knockout mice showed no increases in uterine weights when orally exposed to D4 or estradiol. In an in vitro estrogen receptor binding assay, D4 showed significant competition with 3H-estradiol for binding to estrogen receptor-alpha, but not estrogen receptor-beta. The data presented here indicate that D4 has weak estrogenic activity, and that these effects are mediated through estrogen receptor-alpha.
Keywords
Silicon-compounds; Estrogenic-hormones; Laboratory-animals; Dose-response; Exposure-levels; Animal-studies; Animals; Uterus; In-vitro-studies; Serological-techniques; Peroxidases
Contact
National Institute for Occupational Safety and Health, MS 4020, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
TXAPA9
CAS No.
556-67-2; 541-02-6; 546-56-5; 541-05-9
Publication Date
20031101
Document Type
Journal Article
Email Address
bhm8@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0041-008X
NIOSH Division
HELD; OD
Source Name
Toxicology and Applied Pharmacology
State
NC; WV
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