Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice Michael W. Lieberman, Ernest D. Lykissa, Roberto Barrios, Ching Nan Ou, Geeta Kala, and Subbarao V. Kala Department of Pathology, Baylor College of Medicine, Houston, TX 77030 USA Abstract To examine the toxicity of cyclosiloxanes (CSs) , the predominant low molecular weight cyclic silicones found in breast implants, we injected female CD-1 mice intraperitoneally with different doses of distillate (3.5-35 g/kg body weight) containing cyclosiloxane D3 (hexamethylcyclotrisiloxane ; CS-D3) , cyclosiloxane D4 (octamethylcyclotetrasiloxane ; CS-D4) , cyclosiloxane D5 (decamethylcyclopentasiloxane ; CS-D5) , and cyclosiloxane D6 (dodecamethylcyclohexasiloxane ; CS-D6) . The distillate was found to be lethal and all the mice injected with 35 g/kg died within 5-8 days. The median lethal dose (LD50) for distillate was estimated to be approximately 28 g/kg. These mice developed inflammatory lesions of the lung and liver as well as liver cell necrosis with elevated serum levels of alanine aminotransferase, aspartate aminotransferase, and lactic acid dehydrogenase. Administration of CS-D4 alone also produced lethality in these mice with an LD50 of 6-7 g/kg. CS-D4-treated mice also exhibited pulmonary and hepatic lesions and elevated serum enzymes. Analysis of LD50 data indicates that CS-D4 is about as toxic as carbon tetrachloride or trichloroethylene. We measured hydroxyl radical formation in CS-D4-treated mice and found increases of approximately 20-fold in liver and approximately 7-fold in lung on day 4 following injection. Our findings are significant because in vitro experiments have demonstrated that CSs can migrate out of breast implants, and in mouse experiments CSs have been shown to be widely distributed in many organs after a single subcutaneous injection and to persist for at least a year. Key words: breast implants, cyclosiloxanes, silicone, toxicology. Environ Health Perspect 107:161-165 (1999) . [Online 14 January 1999] http://ehpnet1.niehs.nih.gov/docs/1999/107p161-165lieberman/ abstract.html Address correspondence to M.W. Lieberman, Department of Pathology, Baylor College of Medicine, Houston, TX 77030 USA. We thank Donna Atwood, Susan Goodrum, and Estella Tam for their help with these experiments. This work was supported by a grant from the Consumer Advocates for Product Safety (CAPS) Foundation. Received 28 July 1998 ; accepted 21 October 1998. The full version of this article is available for free in HTML format. |