Safety of Silicone Breast Implants (1999) / Chapter Skim
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4 Silicone Toxicology
4 Silicone Toxicology
Pages 80-113
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From page 80... ...
This chapter identifies silicone compounds as they are listed in individual reports, but it is organized by route of exposure not by type of compound. Silicone fluids, gels, and elastomers are covered since they are components of silicone breast implants.
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From page 81... ...
It is important to note that toxicology studies often report silicone dose levels substantially in excess of any doses that could be achieved on a relative weight basis in women with silicone breast implants. Earlier in this report, the committee emphasizes the relevance of published, peer-reviewed scientific reports and assigns secondary importance to technical reports from industry.
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From page 82... ...
Accumulating qualitative and quantitative data on the general toxicity of silicones, however, allow a reasonable degree of confidence that silicone compounds in breast implants are not hazardous. BRIEF HISTORY OF SILICONE TOXICOLOGY The principles of safety evaluation have not changed much over the past 50 years.
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From page 83... ...
This compound also produced inflammation and necrosis at the sites of subcutaneous and intradermal injections and proved lethal on repeated intraperitoneal injections. Other silicone fluids in the peritoneal cavity elicited only reactions "typical .
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From page 84... ...
Specific studies on breast implant compounds are relied on by the committee for conclusions relevant to the safety of silicone breast implants, however.
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From page 85... ...
Linear polymers of this size are unlikely to be found in breast implants (Kale et al., 1998; reference not found in the original but added for this report, see Chapter 2~. Systemic toxicity after oral, dermal, or inhalation exposure is low.
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From page 86... ...
The compounds have minimal potential for skin irritation. Subchronic studies involving oral administration of the agents did not reveal any systemic toxicity.
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From page 87... ...
Multiple tests found a lack of genotoxicity. Tests for reproductive toxicity following oral or dermal exposure failed to show any clearly positive results.
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From page 88... ...
All of these dose levels are orders of magnitude greater that could be achieved in women with breast implants on a milliliter- or milligram-per-kilogram body weight basis. No immunotoxic potential was identified, although in some studies, adjuvant activity was noted with an increase in humoral but not cell-mediated immunity.
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From page 89... ...
To further elucidate this point, mice were injected subcutaneously or intraperitoneally with 1 ml of Dow Corning 360 silicone fluid, 350 cS, followed by intravenous carbon particles to induce reticuloendothelial blockade. Silicone was found in macrophages in regional lymph nodes in all animals and in macrophages in the adrenal in some intraperitoneally injected animals.
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From page 90... ...
(1971) briefly reported injecting Dow Corning MDX 40411 in amounts ranging from 1 to 500 ml into mice, rats, guinea pigs, rabbits, and monkeys, with the formation of thin capsules, very little tissue reaction, and no systemic effects.
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From page 91... ...
These authors cited others who had injected larger doses intraarterially or intravenously causing embolisms in various organs. Intraperitoneal injections of Dow Corning MD 44011, a silicone fluid that was actually injected in women for breast augmentation (see Chapter 1)
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From page 92... ...
Dogs, examined up to one year after implantation of sponges subcutaneously, intraperiostally, or placed directly onto bone, tolerated the implantation well, and the material was not invaded by bone or periosteum (Marzoni et al., 1959~. Actual breast implant materials, such as Dow Corning Q7-2245 elastomer, in a biological safety screen consisting of tissue cell culture, systemic toxicity, rabbit intracutaneous and pyrogen tests, guinea pig sensitization, and rabbit 90-day implants, elicited no local or systemic responses (Munten et al., 1985)
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From page 93... ...
(1998) in the course of evaluating human fibroblast proliferative responses to smooth and variously textured Dow Corning Medical Grade Silastic found no influence of toxic leachables that might have been released from the silicone samples using 3-~4,5-dimethylthiazole-2-yl)
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From page 94... ...
Surgitek breast implant components, silicone gel-SCL, silicone gelMeme, silicone elastomer SCL, and standard elastomer coated with type A adhesive and polyurethane foam were examined in a two-year rat study with negative (Millipore filters, 0.65-,um pore size) and positive (Millipore filters, 0.025-,um pore size)
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From page 95... ...
It was concluded that implantation of silicone gel-SCL or silicone gel-Meme at a higher dose than usual in humans did not produce any signs of systemic toxicity in female rats (Lemen and Wolfe, 1993~. Most recently, a lifetime implant study with Dow Corning Q7-2159A silicone gel, used in breast implants, tested whether a silicone implant would produce tumors at other than the implant site.
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From page 96... ...
Dow Corning 360 medical-grade fluid, 350 cS, and two other PDMS fluids were administered in comparatively high doses (20, 200, or 12,000 mg/kg) to male and female rats, mice, and rabbits.
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From page 97... ...
. Finally, a two-year gel implant study of Dow Corning Q72159A and Dow Corning MDF-0193 in rats has been reviewed (Ruhr, 1991~.
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From page 98... ...
The reaction of local lymph nodes to injected silicone gel (1.5 ml injected subcutaneously into male Wistar rats) , was measured with rigorous quantitative morphometric techniques at intervals up to 365 days (Tiziani et al., 1995~.
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From page 99... ...
In a recent study, mice received subcutaneous injections of 250 mg of breast implant distillate, a low molecular weight siloxane mixture containing D3, D4, D5, D6, L5, and L6 (Kale et al., 1998~. These materials are released by gel fluid diffusion from breast implants in very low concentrations (see Chapter 3~.
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From page 100... ...
The LD50 for distillate was about 28 g/kg body weight, and for D4 alone 6-7 g/kg body weight (Lieberman et al., 1999~. It is not clear what relevance these studies have for women with silicone breast implants, since test article doses were given that were orders of magnitude greater than possible from breast implants, and LD50s in these ranges have historically been considered indicative of lack of toxicity (Casarett, 1975; Marshall et al., 1981~.
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From page 101... ...
Although some interest in these compounds has been expressed by women with implants or by other investigators, there is no evidence that they are found in silicone breast implants. Oral Exposure Oral toxicity for most silicone compounds is very low.
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From page 102... ...
Some silicone fluids may be absorbed from the gastrointestinal tract. In one male monkey given ~4C-labeled Dow Corning 360 fluid, very little absorption occurred, and more than 90% of the radioactivity was eventually recovered in the feces (Vogel, 1972~.
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From page 103... ...
However, the toxic effects of these compounds have not been observed in experimental silicone gel implant toxicological studies, and there is no evidence that they are present in silicone breast implants. Inhalation Exposure Because silicone compounds are present in hairspray and shampoo, adverse health effects following inhalation of these compounds have been explored.
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From page 104... ...
The effects of inhaled D4 and D5 were also evaluated in reproductive toxicity tests. Male and female rats were exposed to D4 concentrations ranging from 70 to 700 ppm (0.83-8.3 g/m3)
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From page 105... ...
A two-week recovery period was included in the experimental design. There were no test-related effects on survival, clinical condition, body weight gain, food consumption, clinical chemistry, and urinalysis at any exposure level.
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From page 106... ...
. Male and female rats were exposed for four weeks to D4 at airborne concentrations of 70 and 700 ppm.
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From page 107... ...
In an evaluation of the mutagenicity of Dow Corning 7-9172 Part A (used to make gel) with several tester strains, with and without metabolic activation systems, no positive responses were found (Isquith, 1992~.
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From page 108... ...
This compound does not occur in silicone breast implants, however. Early toxicity tests, conducted on a minimum number of animals, showed little if any signs of toxicity for two platinum compounds, Dow Corning Platinum Nos.
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From page 109... ...
It should also be kept in mind that platinum exposure from vehicle exhaust catalysts is increasing and is reflected in serum levels but not in any known health condition (Farago et al., 1998~. The committee could not find any such positive platinum-specific evaluations in women with breast implants and thus finds that evidence is lacking for an association between platinum in silicone breast implants and local or systemic health effects in women who have these implants.
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From page 110... ...
TIN The committee reviewed information bearing on the possible effect of tin on the safety of silicone breast implants. Stannous octoate, stannous oleate or dibutyltin dilaurate catalysts are generally involved in formulation of only part of an implant, e.g., the adhesive sealant in the case of Dow Corning and McGhan Medical or the RTV elastomer shells of saline implants in the case of Mentor and McGhan Medical Corporations.
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From page 111... ...
Meeks, Dow Corning, personal communication, 1999~. Studies of dibutyltin dilaurate found LD50 levels ranging from 85 mg/kg intraperitoneally to between 175 and 1240 mg/kg body weight orally.
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From page 112... ...
In general, there do not appear to be long-term systemic toxic effects from silicone gel implants or from unsuspected compounds in these gels or elastomers detected by these animal experiments. Some have speculated that platinum found in silicone gel and elastomer may be responsible for allergic disease in women with silicone breast implants.
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From page 113... ...
Toxicological studies of tin compounds used in silicone breast implants are scarce, and generally not of parenterally administered tin. The data on organotins indicate that tin catalysts are among the less toxic, and they have not been extractable from implants shells by saline and some organic solvents.
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