Cyclosiloxanes produce fatal liver and lung damage in mice

To examine the toxicity of cyclosiloxanes (CSs), the predominant low molecu lar weight cyclic silicones found in breast implants, we injected female CD -1 mice intraperitoneally with different doses of distillate (3.5-35 g/hg b ody weight) containing cyclosiloxane D3 (hexamethylcyclotrisiloxane; CS-D3) , cydosiloxane D4 (octamethlcyclotetrasiloxane; CS-D4), cyclosiloxane D5 (d ecamethylcyclopentasiloxane; CS-D5), and cyclosiloxane D6 (dodecamethylcycl ohexasiloxane; CS-D6). The distillate was found to be lethal and all the mi ce 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 devel oped inflammatory lesions of the lung and liver as well as liver cell necro sis with elevated serum levels of alanine aminotransferase, aspartate amino transferase, and lactic acid dehydrogenase. Administration of CS-D4 alone a lso produced lethality in these mice with an LD50 of 6-7 g/kg. CS-D4-treate d mice also exhibited pulmonary and hepatic lesions and elevated serum enzy mes. 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-veated mice and found increases of approximately 20-fold in liver and approximately 7-fold in lung on day 4 following injection. Our finding s are significant because in vitro experiments have demonstrated that CSs c an migrate out of breast implants, and in mouse experiments CSs have been s hown to be widely distributed in many organs after a single subcutaneous in jection and to persist for at least a year.