Octamethylcyclotetrasiloxane Exhibits Estrogenic Activity in Mice via ERalpha

Details

• Personal Author:
  Germolec DR ; He B ; Korach KS ; Meade BJ ; Miller MR ; Munson AE ; Rhodes-Brower S ; Walker VR
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Estrogens Laboratories Occupational Health Safety Silicon Compounds Urogenital System
• Keywords:
  Animal-studies Dose-response Estrogenic-hormones Exposure-levels In-vitro-studies Laboratory-animals Peroxidases Serological-techniques Silicon-compounds Uterus
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; OD - Office of the Director
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  254-261
• Volume:
  192
• Issue:
  3
• NIOSHTIC Number:
  nn:20032133
• Citation:
  Toxicol Appl Pharmacol 2003 Nov; 192(3):254-261
• Contact Point Address:
  National Institute for Occupational Safety and Health, MS 4020, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  bhm8@cdc.gov
• CAS Registry Number:
  Decamethylcyclopentasiloxane (CAS RN 541-02-6) ; Hexamethylcyclotrisiloxane (CAS RN 541-05-9) ; Octamethylcyclotetrasiloxane (CAS RN 556-67-2) ; Octaphenylcyclotetrasiloxane (CAS RN 546-56-5)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f157a935ceb0fca0fec66abfe43dccb21c8e93a505bc8942e9d3c84fcfbf01dc05971a049144580e25f3a8e25b163cd7756579dec62e13ee173b73e14890e30e
• Download URL:
  https://stacks.cdc.gov/view/cdc/186181/cdc_186181_DS1.pdf
• File Type:
  [PDF - 370.15 KB ]