The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
There is widespread use of silicone-containing medical devices in many surgical and medical specialties. A variety of aesthetic and reconstructive prostheses contain silicone such as breast, chin, ear and joint prostheses. There are silicone hydrocephalus shunts, fallopian tube clips, cardiac valves, drug release capsules and intraocular lenses to name just a few of the many applications of implantable silicone. It is estimated that, prior to FDA sanctions, 130,000 American women had breast implantation procedures. Non-implantable applications of silicone include their use in tubing for drains, catheters, dialysis machines and blood oxygenators.
There is a paucity of data available on the status of the immune system in the presence of silicone implants. These studies were designed to determine the potential effects of silicone on the immune system and host resistance to selected microbial and tumor models.
These studies were NOT designed to determine the potential immunogenicityof the silicone implants. However, it is possible that if present,continuous antigenic stimulation may alter some of the immuneassays that were performed in these experimental animals.
These studies were conducted over a 3 year period. The initial protocol was approved and studies conducted between 23 Oct 89 and 19 Apr 90. Since there were no dose-response studies in the initial protocol, additional dose-response studies were carried out when statistical significance occurred. In addition a study was conducted to clarify the Natural Killer Cell results. The dose levels and the duration of exposure were based on the known and perceived use. For the silicone fluid and gel, one ml was selected which was estimated to represent 1/20 of the body weight of the mouse. There were 2 study durations. A 10-day exposure period was selected because it is the peak time of the initial inflammatory response. The 180-day study provides for evaluation of the immune status during the chronic phase where the capsule is well formed. The studies reported here are for the 180-day implantation period. Studies related to 10 days of implantation are in a separate report entitled, "Immmunotoxicity of Silicone in Female B6C3F1 Mice - 10 Day Exposure."
The baseline toxicology data are summarized in Table ES-1. The primary objective of the toxicology studies was to characterize the toxicological profile produced by treatment with silicone. Subcutaneous implantation of the silicone preparation produced no significant changes in any of the parameters measured. There was no implant-related mortality from exposure and no overt signs of toxicity. There were no gross pathologic findings at the time of necropsy. For the most part, body weight and body weight gain were not altered by the implants. Selected hematologic and serum chemistry parameters were not different from the vehicle control group and were within the historical control range of the MCV Immunotoxicology Program. Body weight was not adversely affected by the silicone implant. There were no significant changes in the weight of the brain, liver, spleen, thymus, lungs or kidneys. Bone marrow cellularity, CFU-M and CFU-GM stem cells were unaffected by the implants.
Table ES-2 summarizes the immunology studies. Implantation of mice with silicone preparations produced no effects on indicators of humoral immunity, such as changes in B cell number, proliferative ability or ability to differentiate into antibody-producing cells to a T-dependent antigen. Indicators of cell-mediated immunity were also unaffected as seen in a lack of effect on T lymphocyte numbers and subset analysis, and spleen cell response to the T-dependent antigen, indicating that the regulatory T cells were similar tothose of control mice. Proliferative capacity, as measured byresponse to T cell mitogens and to allogeneic cells, was unaffected by silicone implants. Differentiation and the killing mechanism of T cells were intact as seen in a CTL response. Indicators of innate immunity that were unaffected included macrophage numbers and function and complement activity. Changes in natural killer cell function were slightly decreased.
Table ES-3 summarizes the three host resistance studies that were conducted. Implantation of mice with the silicone preparations did not produce any changes in host resistance to two bacterial models or one tumor host resistance model.