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SILICONES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Silicones are used in adhesives, antifoaming agents, ceramics, cosmetics, glass, hydraulic fluids, medical implants, dielectrics, and lubricants. Silicones are chains of alternating silicon and oxygen atoms which have various organic groups added. The amount of cross linkage determines whether the polymer is a solid, an elastomer or fluid. Subcutaneous injection of silicone fluid has also been used illicitly for physical enhancement by men and women.
    B) Simethicone is used orally in treatment of flatulence, abdominal distension, and topically as a skin protectant.
    C) This management does not address the very irritating and potentially corrosive chlorosilanes and ethoxysilanes.

Specific Substances

    A) SILICONE
    1) Siloxane
    2) Siloxanes
    3) Molecular Formula: R2-Si-O
    4) Organosiloxane
    DIMETHICONE
    1) NIOSH/RTECS TW 2690000
    2) PDMS
    3) Polydimethyl siloxane
    4) Dimethylpolysiloxane
    5) CAS 9006-65-9
    SIMETHICONE
    1) Activated dimethicone
    2) Dimethyl polysiloxane
    3) Antifoam A
    4) Simeticonum
    5) CAS 8050-81-5
    CYCLOMETHICONE
    1) Cyclosiloxanes, di-Me
    2) Cyclohexasiloxane
    3) Cycloheptasiloxane
    4) Cyclotetrasiloxane
    5) Cyclopentasiloxane
    6) Cyclopolydimethylsiloxane
    7) Dimethylcyclopolysiloxane
    8) Dow corning 344
    9) Dow corning 344 fluid
    10) Dow corning X 2-1401
    11) KF 993
    12) Polydimethyl siloxy cyclics
    13) Q 2-1401
    14) SWS 03314
    15) SWS-F 222
    16) X 2-1401
    GENERAL TERMS
    1) Crystalon

Available Forms Sources

    A) FORMS
    1) Brand names for dimethicone include Covicone, Silastic 200, Silicote.
    2) Simethicone is available as 40 to 125 mg tablets and drops containing 40 mg/0.6 mL. Brand names include Mylicon(R), Gas-X(R), Silain(R), and Phazyme(R), Aeropax(R), Antifoam A(R), Baros(R), Bicolon(R), Delesan(R), Meteorex(R), MS Antifoam M(R), Mylocon(R), Ovol(R), Phasil(R), and Polysilcon(R).
    B) USES
    1) Silicone is used to lubricate single-use insulin syringes. Collier & Dawson (1985) demonstrated that 1 mL of U-100 regular insulin stored at 25 degrees C for 24 hours in a 1 mL syringe lubricated with less than 1.5 mg of liquid silicone will contain 30 to 40 mcg when expelled.
    2) Silicone is present in domestic cleaning powders such as Ajax(R), which is 90% silica crystals (silicon dioxide crystals) (Dumontet et al, 1991; Hawley, 1981).
    3) Silicone oil 5000 centistokes (AdatoSil 5000(R) intravitreal injection) is used for retinal tamponade following or in conjunction with surgery in complicated or persistent detachment of the retina (S Sweetman , 2001; Pastor et al, 1998).
    4) Simethicone has been used as an adjunct in the treatment of various clinical conditions in which gas retention may be a problem including postoperative gaseous distention, air swallowing, dyspepsia, infant colic, peptic ulcer, spastic or irritable colon, and diverticulitis. Simethicone-coated cellulose suspension is used in conjunction with ultrasound imaging to enhance the delineation of upper abdominal anatomy by reducing gas shadowing (S Sweetman , 2001; Gilman et al, 1990).
    5) Silicone fluid (polydimethylsiloxane) has been used illegally as a tissue filler for subcutaneous injection by both males and females. It is reportedly used by bodybuilders, male-to-female transsexuals for body feminization and by females for physical enhancement. Reported sites of injection have included the gluteal and trochanteric regions, pectoralis muscles, breasts, arms and vaginal wall. The illicit use of large volumes (up to 1 liter) of silicone fluid have been associated with silicone pulmonary embolism, acute alveolar hemorrhage, and death (Restrepo et al, 2009).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Silicone is used to make consumer products and medical implants. It is used as a filler in breast implants. It has been injected directly into tissue for cosmetic purposes, although this is not a medically approved use. Simethicone is used to treat colic and gaseous distension.
    B) PHARMACOLOGY: Simethicone is though to decrease gaseous distension by decreasing surface tension of gas bubbles in the GI tract.
    C) TOXICOLOGY: Silicones are generally not toxic, but injection may result in local granuloma formation. Systemic absorption of a large amount may produce silicone pulmonary embolism.
    D) EPIDEMIOLOGY: Environmental exposure is common. Injection for cosmetic purposes is uncommon. Life-threatening effects are very rare.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Ingestion is not expected to produce significant toxicity. Injection may produce local tissue granuloma formation.
    2) SEVERE TOXICITY: Direct injection into tissue can cause a severe systemic reaction with fever, pneumonitis, widespread microemboli and associated tissue infarction (primarily lungs but also intestines, liver, brain and heart), acute lung injury, and alveolar hemorrhage. Fatalities have been reported.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Fever and febrile illness have been reported following silicone injection or implantation.
    0.2.6) RESPIRATORY
    A) Silicone injection has been associated with the development of fatal pulmonary edema, pneumonitis, pleural effusion, ARDS and dyspnea.
    0.2.9) HEPATIC
    A) Granulomatous hepatitis has occurred following silicone injection.
    0.2.10) GENITOURINARY
    A) Renal failure was reported in one patient after augmentation mammoplasty.
    0.2.14) DERMATOLOGIC
    A) Hypopigmentation and peau d'orange skin changes have been reported after silicone injection or implantation.
    0.2.21) CARCINOGENICITY
    A) Two large studies have not found an increase in cancer among patients with silicone breast implants.

Laboratory Monitoring

    A) Routine laboratory studies are generally not needed.
    B) Obtain a chest x-ray in patients with pulmonary symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Minimal symptoms are expected and no specific care is required.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Patients with symptoms of pulmonary embolism may require ventilator support for hypoxia.
    C) DECONTAMINATION
    1) Decontamination is not indicated. Surgical excision may be considered for severe tissue reactions to injected silicone.
    D) ANTIDOTE
    1) None.
    E) ENHANCED ELIMINATION
    1) There is no role for enhanced elimination.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: If patients are symptomatic following an acute unintentional ingestion they can be followed at home.
    2) OBSERVATION CRITERIA: Patients who are symptomatic, patients who have injected silicone, and those with deliberate ingestions, should be referred to a healthcare facility.
    3) ADMISSION CRITERIA: Patients who remain persistently symptomatic should be admitted and monitored for worsening respiratory symptoms.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing respiratory symptoms.
    G) PHARMACOKINETICS
    1) Silicone is not well absorbed following oral administration. Silicone may distribute over hours producing delayed symptoms following injection. However, in most cases the silicone will remain at the site of injection. Simethicone is not absorbed following oral administration.
    H) PITFALLS
    1) Failure to recognize that injection may result in pulmonary embolism and systemic toxicity. Packets of silicone can create the same problems as any other foreign body, if ingested or aspirated.
    I) DIFFERENTIAL DIAGNOSIS
    1) Injection of other materials, pulmonary embolism.
    0.4.3) INHALATION EXPOSURE
    A) Inhalation hazard is low due to the low vapor pressure of most silicone fluids. Treatment is symptomatic and supportive.
    0.4.6) PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive.
    B) Monitor cardiac rhythm as indicated.

Range Of Toxicity

    A) TOXIC DOSE: Ingestion does not cause systemic toxicity, although packets may cause foreign body effects. Most cases of severe toxicity are associated with injection of large volumes of silicone oil.

Clinical Effects

Summary Of Exposure

    A) USES: Silicone is used to make consumer products and medical implants. It is used as a filler in breast implants. It has been injected directly into tissue for cosmetic purposes, although this is not a medically approved use. Simethicone is used to treat colic and gaseous distension.
    B) PHARMACOLOGY: Simethicone is though to decrease gaseous distension by decreasing surface tension of gas bubbles in the GI tract.
    C) TOXICOLOGY: Silicones are generally not toxic, but injection may result in local granuloma formation. Systemic absorption of a large amount may produce silicone pulmonary embolism.
    D) EPIDEMIOLOGY: Environmental exposure is common. Injection for cosmetic purposes is uncommon. Life-threatening effects are very rare.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Ingestion is not expected to produce significant toxicity. Injection may produce local tissue granuloma formation.
    2) SEVERE TOXICITY: Direct injection into tissue can cause a severe systemic reaction with fever, pneumonitis, widespread microemboli and associated tissue infarction (primarily lungs but also intestines, liver, brain and heart), acute lung injury, and alveolar hemorrhage. Fatalities have been reported.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Fever and febrile illness have been reported following silicone injection or implantation.
    3.3.3) TEMPERATURE
    A) FEVER has been reported following subcutaneous silicone injection and implantation of silicone gel breast prostheses (Restrepo et al, 2009; Villa & Sparacio, 2000; Manresa & Manresa, 1983; Chastre et al, 1983; Uretsky et al, 1979; Ellenbogen et al, 1975).
    1) An acute systemic febrile illness developed in one patient following injection of silicone under each breast. The patient died ten hours post injection (Ellenbogen et al, 1975).

Heent

    3.4.3) EYES
    A) Intraocular injection of silicone oil has been associated with the following complications: ocular hypotension (less than 13 mmHg), sustained ocular hypertension (greater than 23 mmHg), acute hypertensive peaks (greater than 30 mmHg), corneal alterations, emulsifications, silicone oil cloudiness and preretinal reproliferations. Highly purified silicone oil was associated with less complications than the less purified oil (Pastor et al, 1998).
    B) Intravitreal injection of liquid silicone for retinal tamponade, following or in conjunction with retinal detachment surgery, was associated with cataract, glaucoma, and keratopathy (S Sweetman , 2001).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ENDOCARDITIS
    1) WITH THERAPEUTIC USE
    a) Travis et al (1986) reported silicone-induced endocarditis as a complication of longstanding transvenous cardiac pacing catheterization. Thrombotic vegetations on the tricuspid valve were shown to be embedded with silicone.
    B) THROMBOEMBOLIC DISORDER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: One day after receiving an injection of an unknown volume of silicone fluid in the trochanter areas, a 28-year-old transsexual man (seropositive to HIV-1 antibody) developed nausea, vomiting, fever (38.5 degrees C), mild dyspnea (respiratory rate 36 beats per minute), cough, hemoptysis, and tachycardia (heart rate 160 beats per minute). He experienced progressive worsening of pulmonary bleeding, respiratory failure, and coma. He died 35 hours after admission. Autopsy showed pulmonary, myocardial, cerebral, intestinal, and hepatic infarcts secondary to microthromboembolism; hemorrhagic pleuritis, hemopericardium, surrenal, multifocal subarachnoid and gastrointestinal bleeding; venous pudendum plexus thrombosis. Clinical presentation and histopathological picture suggested a diagnosis of tissue damage with disseminated intravascular coagulation secondary to silicone-related multiple micro-embolisms (Villa & Sparacio, 2000).

Respiratory

    3.6.1) SUMMARY
    A) Silicone injection has been associated with the development of fatal pulmonary edema, pneumonitis, pleural effusion, ARDS and dyspnea.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: One patient developed severe acute bilateral pulmonary edema and died ten hours after silicone was injected under each breast. Autopsy revealed silicone in all organs (2.7 to 120 mg/100 mL) with 4000 mg/100 mL found in the lungs (Ellenbogen et al, 1975).
    b) CASE REPORT: Adult respiratory distress syndrome developed in one patient following subcutaneous silicone injection for augmentation mammoplasty (Celli & Kovnat, 1983). ARDS and evidence of embolization of silicone in the lungs and brain was observed on autopsy in a transsexual man after receiving multiple silicone injections. Pulmonary symptoms developed within several hours of exposure and he died 22 days later once mechanical ventilation was stopped (Clark et al, 2008).
    B) ACUTE PNEUMONITIS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Acute pneumonitis developed in three patients 24 hours after subcutaneous silicone injection. Chest x-ray showed bilateral interstitial infiltrates with patchy air space consolidation. One patient required intubation and mechanical ventilation. All cases resolved within 5 to 14 days (Chastre et al, 1983).
    b) CASE SERIES: Seven patients developed acute pneumonitis with hemoptysis, dyspnea and fever after subcutaneous injection of 100 to 250 ml of silicone for breast augmentation. Chest x-ray showed bilateral alveolar infiltrates and scattered air space consolidation. The only treatment provided was nasal oxygen and all patients recovered within 10 days (Lai et al, 1994).
    c) CASE REPORT: Silicone-induced acute pneumonitis developed in a woman with a history of infiltrating ductal breast carcinoma and a silicone gel mammary prosthesis that was placed 9 years prior to presentation. Chest x-ray showed pulmonary infiltrates and silicone in alveolar histiocytes and small blood vessels by lung biopsy. Rupture of the silicone implant was confirmed at the time of surgical removal. The patient was treated with a course of steroids with complete recovery (Paredes Vila et al, 2010).
    d) CASE REPORT: A 30-year-old woman presented with progressive shortness of breath and cough over the previous 10 days. For cosmetic augmentation, she had received 2 silicone injections (amount unknown) in her buttocks 12 days and 2 days prior to admission. Initial evaluation revealed an oxygen saturation of 63% while breathing ambient air, pulse 119 BPM, blood pressure 98/66, and respiratory rate of 20 breaths per minute. Rhonchi were heard throughout the lungs on auscultation; chest x-ray showed infiltrates in the lower left lobe. Arterial blood gases revealed respiratory alkalosis and pronounced hypoxemia. The patient was intubated electively and 100 mL of bright red blood was aspirated from the endotracheal tube. An open lung biopsy showed lipoid vacuoles compatible with silicone pneumonitis. The presence of elemental silicone within the vacuoles was confirmed. She was treated with methylprednisolone 250 mg IV every 6 hours for 5 days then gradually tapered. On day 7 she was extubated and her oxygen saturation remained at 98% to 100% (Gurvits, 2006).
    e) CASE REPORT: A 45-year-old transsexual man with a history of HIV developed multi-system organ failure after multiple subcutaneous silicone injections due to embolization of the lungs, brain and heart. Within several hours of injections, the patient developed difficulty breathing and was lethargic but arousable. An initial ECG and chest x-ray were normal. Within 2 hours of admission, pulmonary function rapidly deteriorated requiring intubation. The patient also became obtunded. A repeat chest x-ray showed bilateral pulmonary infiltrates. Despite mechanical ventilation, hypoxia continued with no change in neurologic function. A tracheostomy was placed on day 10; cultures remained negative for bacteria, mycobacteria and viruses. Several CT scans of the brain showed mild edema, but no other focal findings. By day 22 in consultation with the family, mechanical ventilation was stopped and the patient died that day. Autopsy demonstrated pneumonia, ARDS, and foreign body giant cells reactions to round optically clear material in the lungs and in the heart, massive amounts of silicone were found in the hips and buttocks region (Clark et al, 2008).
    1) CASE REPORT: A second man also received subcutaneous silicone injections and developed increasing respiratory difficulty and was intubated. An initial chest x-ray was negative, but gradually worsened showing mild pulmonary infiltrates. His oxygen requirements remained stable during mechanical ventilation and he was extubated successfully by day 10. No permanent sequelae occurred (Clark et al, 2008).
    C) PLEURAL EFFUSION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Bilateral pleural effusions developed in a woman following silicone gel breast prostheses implantation. Treatment included prednisone 40 mg daily. Slight pleural thickening continued 3 months after the implantation (Manresa & Manresa, 1983).
    D) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) Dyspnea has been reported following subcutaneous silicone injection and implantation of silicone gel breast prostheses (Manresa & Manresa, 1983; Chastre et al, 1983)
    E) PULMONARY EMBOLISM
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES
    1) In a retrospective review of 10 patients with silicone-induced pulmonary embolism, all 10 patients presented with acute respiratory distress along with fever in 5 cases. The cases included 8 men (6 male-to-female transsexuals) and 2 women who intentionally injected massive amounts of a highly viscous agent purportedly containing a silicone oil. Severe respiratory insufficiency requiring intubation and mechanical ventilation occurred in 6 patients, with 2 fatalities reported. The onset of respiratory symptoms following subcutaneous silicone injection was highly variable (i.e., 15 minutes up to 2 days). Alveolar hemorrhage was confirmed in all 6 patients that underwent bronchoalveolar lavage or transbronchial biopsy. Chest CT findings consistently demonstrated consolidation (n=7) and bilateral peripherally distributed ground-glass opacities along with interlobular septal thickening in all 10 patients. Several risk factors for the development of silicone pulmonary embolism included the use of high volumes of silicone fluid (up to 1 liter) and manipulation of the skin following the injection (Restrepo et al, 2009).
    b) CASE REPORTS
    1) CASE REPORT: Silicone pulmonary emboli were diagnosed in a patient receiving silicone injections for breast augmentation. Transbronchial biopsies were positive for multiple deposits of nonstaining foreign material in the interstitium and alveolar capillary walls. Globular deposits typical of silicone in the alveolar wall and capillaries and within alveolar macrophages were seen on electron microscopy. The patient recovered with supportive care (Duong et al, 1998).
    2) CASE REPORT: Rodriguez et al (1989) report a fatality from repeated silicone injections into the breast and hips resulting in lung embolism. Silicone in the lung vacuoles was identified by scanning electron microscopy with energy dispersive x-ray analysis.
    3) CASE REPORT: A 45-year-old transsexual man with a history of HIV developed multi-system organ failure after multiple subcutaneous silicone injections due to embolization of the lungs, brain and heart. Within several hours of injections, the patient developed difficulty breathing and was lethargic but arousable. An initial ECG and chest x-ray were normal. Within 2 hours of admission, pulmonary function rapidly deteriorated requiring intubation. The patient also became obtunded. A repeat chest x-ray showed bilateral pulmonary infiltrates. Despite mechanical ventilation, hypoxia continued with no change in neurologic function. A tracheostomy was placed on day 10; cultures remained negative for bacteria, mycobacteria and viruses. Several CT scans of the brain showed mild edema, but no other focal findings. By day 22 in consultation with the family, mechanical ventilation was stopped and the patient died that day. Autopsy demonstrated pneumonia, ARDS, and foreign body giant cells reactions to round optically clear material in the lungs and in the heart, massive amounts of silicone were found in the hips and buttocks region (Clark et al, 2008).
    a) CASE REPORT: A second man also received subcutaneous silicone injections and developed increasing respiratory difficulty and was intubated. An initial chest x-ray was negative, but gradually worsened showing mild pulmonary infiltrates. His oxygen requirements remained stable during mechanical ventilation and he was extubated successfully by day 10. No permanent sequelae occurred (Clark et al, 2008).
    4) CASE REPORT: Several hours after injection of an unknown amount of silicone fluid in the trochanter areas, a 26-year-old transsexual man developed dyspnea and palpitations. Mild interstitial infiltration was noted on the chest roentgenogram. Chest CT scan revealed diffuse infiltrates involving prevalently peripheral lung field of inferior lobes; perfusion lung scintiscan showed a probability for pulmonary embolism. He recovered with supportive care (Villa & Sparacio, 2000).
    5) CASE REPORT: One day after receiving an injection of an unknown amount of silicone fluid in the trochanter areas, a 28-year-old transsexual man developed nausea, vomiting, fever (38.5 degrees C), mild dyspnea (respiratory rate 36 bpm), cough, hemoptysis, and tachycardia (heart rate 160 bpm). Arterial blood gas analysis without oxygen therapy revealed pH 7.435, PaO2 42.9 mmHg, and PaCO2 37.9 mmHg. Bilateral diffuse interstitial infiltration was noted on the chest roentgenogram (Villa & Sparacio, 2000).
    a) Laboratory tests revealed leukocytosis (WBC 15,900/mm(3)) and aspecific coagulation alterations (prothrombin time 52%, partial thromboplastin time 32 seconds and a normal platelet count). Later blood tests showed seropositivity to HIV1-antibody with fail of T-helper lymphocytes and progressive reduction of platelets count. He experienced progressive worsening of pulmonary bleeding, respiratory failure, and coma. He died 35 hours after admission.
    b) Autopsy showed pulmonary, myocardial, cerebral, intestinal, and hepatic infarcts secondary to microthromboembolism; hemorrhagic pleuritis, hemopericardium, surrenal, multifocal subarachnoid and gastrointestinal bleeding; venous pudendum plexus thrombosis. Histological examination of these organs revealed characteristic ischemic and hemorrhagic lesions with the presence of interstitial and perivascular histiocytes containing vacuolar nonstaining cytoplasmic inclusions. Clinical presentation and histopathological picture suggested a diagnosis of tissue damage with disseminated intravascular coagulation secondary to silicone-related multiple micro-embolisms (Villa & Sparacio, 2000).
    F) LACK OF EFFECT
    1) Inhalation hazard is low due to the low vapor pressure of most silicone fluids (Stokinger, 1981).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PULMONARY FIBROSIS
    a) DOGS: Both focal and diffuse pulmonary fibrosis, has been seen in long-term studies on dogs (Celli & Kovnat, 1983).
    b) MICE: Inflammatory lesions of the lungs were reported following injections of cyclosiloxanes in mice. On the fourth day after the injections, an approximate fold increase of hydroxyl radical formation in the lungs was noted (Lieberman et al, 1999).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) LACK OF EFFECT
    1) Nyren et al (1998) examined the risk of neurological disorders in women with silicone breast implants. A cohort of 7433 women with implants was compared to a cohort of 3351 who underwent breast reduction surgery as a control. The authors found no support for the conjecture that breast implants cause neurologic disorders (Nyren et al, 1998). In other similar studies, authors have also found a lack of support for the hypothesis of silicone-induced neurologic disease (Winther et al, 1998; Ferguson, 1998; Ferguson, 1997).

Hepatic

    3.9.1) SUMMARY
    A) Granulomatous hepatitis has occurred following silicone injection.
    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) GRANULOMATOUS hepatitis has occurred in several patients following silicone injection (Chastre et al, 1983; Ellenbogen et al, 1975).
    2) Hepatic inflammation, fibrosis and granulomatous hepatitis have occurred in a few cases of patients on long-term dialysis in which silicone tubing use was routine (Bommer et al, 1981; Leong et al, 1982; Hunt et al, 1989). Silicone has been noted in the liver up to 4 years after completion of dialysis.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) NMR animal studies have indicated migration, aging and metabolism of silicone following injection or implantation. Silicone and its metabolites were identified in the livers and spleens of Sprague-Dawley rats (Garrido et al, 1993; Pfleiderer et al, 1993).
    1) Silicone oil was injected into the necks of three of the rats to assess the accelerated migration and degradation of free silicone in vivo. Model implants were surgically placed in the lower-backs of 23 rats to follow the aging process of gel-filled implants over time (Pfleiderer et al, 1993).
    b) Silicone nuclear magnetic resonance (NMR) spectroscopy revealed migration of silicone particles from subcutaneous injections and from surgical silicone gel implants into the liver in rats. The authors demonstrated that silicones are not metabolically inert (Garrido et al, 1993).
    2) HEPATIC NECROSIS
    a) Liver cell necrosis was reported in mice following injections of cyclosiloxanes. Hydroxy radical formation was increased approximately 20-fold in the liver of these mice. Hepatic lesions and elevated serum enzymes were reported in all mice (Lieberman et al, 1999).

Genitourinary

    3.10.1) SUMMARY
    A) Renal failure was reported in one patient after augmentation mammoplasty.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: One case of renal failure following silicone augmentation mammoplasty has been reported. The patient recovered within 6 days of removal of the implants (Uretsky et al, 1979).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) DISSEMINATED INTRAVASCULAR COAGULATION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: One day after receiving an injection of an unknown volume of silicone fluid in the trochanter areas, a 28-year-old transsexual man developed nausea, vomiting, fever (38.5 degrees C), mild dyspnea (respiratory rate 36 bpm), cough, hemoptysis, and tachycardia (heart rate 160 bpm). Arterial blood gas analysis without oxygen therapy revealed pH 7.435, PaO2 42.9 mmHg, and PaCO2 37.9 mmHg. Bilateral diffuse interstitial infiltration was noted on the chest roentgenogram.
    1) Laboratory tests revealed leukocytosis (WBC 15,900/mm(3)), aspecific coagulation alterations (prothrombin time 52%, partial thromboplastin time 32 seconds and a normal platelet count). Later blood tests showed seropositivity to HIV-1antibody with fail of T-helper lymphocytes and progressive reduction of platelets count. He experience progressive worsening of pulmonary bleeding and of respiratory failure, followed by disturbances of consciousness until coma. He died 35 hours after admission.
    2) Autopsy showed pulmonary, myocardial, cerebral, intestinal, and hepatic infarcts secondary to microthromboembolism; hemorrhagic pleuritis, hemopericardium, surrenal, multifocal subarachnoid and gastrointestinal bleeding; venous pudendum plexus thrombosis. Histological examination of these organs revealed characteristic ischemic and hemorrhagic lesions with the presence of interstitial and perivascular histiocytes containing vacuolar nonstaining cytoplasmic inclusions. Clinical presentation and histopathological picture suggested a diagnosis of tissue damage with disseminated intravascular coagulation secondary to silicone-related multiple micro-embolisms (Villa & Sparacio, 2000).

Dermatologic

    3.14.1) SUMMARY
    A) Hypopigmentation and peau d'orange skin changes have been reported after silicone injection or implantation.
    3.14.2) CLINICAL EFFECTS
    A) DISCOLORATION OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Hypopigmentation has occurred following illicit injections of silicone (Ellenbogen et al, 1975).
    b) CASE REPORT: Rock-hard, red breasts with overlying inflammation and peau d'orange skin changes were noted in a 36-year-old woman who had received silicone breast injection (Ellenbogen et al, 1975).
    B) SKIN ULCER
    1) WITH THERAPEUTIC USE
    a) Large volume subcutaneous silicone injections, for cosmetic reasons, have resulted in leg ulcers 23 years after the injections. Silicone was identified, via energy-dispersive spectroscopy, in amorphous spherules within the vacuoles in the dermis (Rae et al, 1989).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) WITH THERAPEUTIC USE
    a) Rheumatic complaints are reported more frequently by women with silicone implants but no evidence exists to support a causal relationship (Giltay et al, 1994).
    B) SYNOVITIS
    1) WITH THERAPEUTIC USE
    a) Silicone synovitis has been reported as soon as 3 months following insertion of an implant for degenerative arthritis. Clinical features may include pain, loss of joint function, and swelling in the area of the affected joint. Also, calcification in regional soft tissue, including joint capsules, may also occur (Christie et al, 1989).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LYMPHADENOPATHY
    1) WITH THERAPEUTIC USE
    a) CASE SERIES: Lymphadenopathy occurred in a 56-year-old woman and a 50-year-old woman 4 and 1/2 years following metacarpal-phalangeal joint replacement with silicone elastomer prostheses (Kircher, 1980).
    B) BIOPSY FINDING
    1) WITH THERAPEUTIC USE
    a) An increase in local hyaluronic acid and interleukin-2 was identified in capsular biopsies of silicone breast implant recipients versus normal breast tissue.
    1) It was undetermined whether HYA and IL-2 increases occur as a response to silicone leakage or as a normal foreign body inflammatory (Wells et al, 1994).
    C) DISORDER OF IMMUNE FUNCTION
    1) WITH THERAPEUTIC USE
    a) SUMMARY: The literature supporting a link between silicone breast implants and the development of autoimmune disorders consists of case reports and case series; such data is not sufficient to determine causality. Several large cohort studies and case control studies have NOT found an association between silicone breast implants and signs and symptoms of autoimmune and rheumatologic diseases (Wolfe & Anderson, 1999; Karlson et al, 1999; Gabriel et al, 1994; Sanchez-Guerrero et al, 1995; Hochberg et al, 1995) Englert et al, 1994; (Dugowson et al, 1992; Strom et al, 1994; Williams et al, 1997).
    1) A meta-analysis that included 9 cohort studies, 9 case-control studies and 2 cross-sectional studies found no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatologic conditions (Janowsky et al, 2000).
    2) At this point a causal relationship between silicone implants and autoimmune and connective tissue disorders is NOT supported by the available evidence.
    3) Its been observed that women with extracapsular silicone (silicone gel outside of the fibrous scar that forms around breast implants) were more likely to report having fibromyalgia or other connective tissue diseases (e.g., dermatomyositis, polymyositis, Hashimoto's thyroiditis, pulmonary fibrosis, eosinophilic fasciitis, mixed connective tissue diseases, and polymyalgia) than other women in the study (Brown et al, 2001).
    b) SILICONOSIS: This term is used to describe a spectrum of illnesses speculated to be associated with silicone breast implants in women. Most commonly, siliconosis is an undifferentiated connective tissue disease or musculoskeletal pain syndrome characterized by significant fatigue, arthralgias, and myalgias. Fever is usually absent. Approximately one-third of these patients have abnormal laboratory tests, including ANAs.
    1) Other symptoms allegedly associated with siliconosis have included skin rash, alopecia, lymphadenopathy, and arthritis. A significant number of patients experience a Sjogren's-like disorder, characterized by xerophthalmia and xerostomia, but with an absence of autoantibodies and cellular infiltrates. Systemic lupus-like syndrome may be evident in some patients with arthralgias, skin rash and fever in the absence of detectable ANA. Inflammatory responses may occur due to foreign body reactions and seepage through intact membranes.
    2) Neurologic symptoms, with short-term memory loss, paresthesias, and neuropathy have also been reported, but again the relationship with silicone implants has not been supported by large cohort studies (Nyren et al, 1998; Winther et al, 1998; Ferguson, 1998; Ferguson, 1997).
    3) Improvement of symptoms has been reported in some patients following removal of the implants. Antisilicone antibodies have not been reported. No differences were apparent between disruption rates of implants between those patients relating symptoms to the implants and those who did not. Inadequate evidence exists to support a causal relationship.(Borenstein, 1994; Vasey et al, 1994; Solomon, 1994; Freundlich et al, 1994; Press et al, 1992; Ellis et al, 1997; Robinson et al, 1995; Peters, 1995; Fenske et al, 1994; Thomsen et al, 1990).
    c) GRANULOMAS: Encapsulating foreign body reactions to silicone leaking from implants, or from ruptured implants, may result in localized granulomatous masses. These mass lesions have been referred to as siliconomas. Another type of mass sometimes found near breast implants is a seroma, a collection of serous fluid or plasma with differing amounts of cellular infiltrates (Teuber et al, 1999; Busch, 1994; Cruz et al, 1985).
    1) Kasper & Chandler (1994) identified talc crystals in 71% of patients within nodular granulomas and perivascular histiocytes. The authors speculate the high incidence of talc deposition surrounding silicone implants implies that talc is a contaminant, either introduced at the time of implant surgery, or released into tissues as a silicone gel contaminant during gel bleed.
    D) CALCINOSIS
    1) WITH THERAPEUTIC USE
    a) Calcification of silicone-gel breast implant capsules presents as discrete calcified plaques on the inside surface of the capsules (Hardt et al, 1994), and is usually related to length of the implant period. Generally, calcification is not seen with implants less than 10 years old. Peters & Smith (1995) reported 26.1% of patients had calcifications from implants inserted for 11 to 20 years.
    E) ANTIBODY
    1) WITH THERAPEUTIC USE
    a) In one study, Jensen et al (2003) reported that silicate antibodies were not consistently associated with silicone breast implants and were not correlated with rheumatic symptoms (Jensen et al, 2003)
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ARTHRITIS
    a) MICE: Schaefer et al (1997) determined the influence of silicone implantation on collagen-induced arthritis and the immune response to type II collagen following silicone implantation in mice. In the mouse model of arthritis it was determined that autoantibodies against silicone-bound proteins probably did not have pathologic significance. The incidence or severity of arthritic disease did not increase as compared to controls.
    b) RATS: Yoshino (1994) administered intra-articular injections of silicone into ankle joints of rats, which induced a chronic arthritis. Immunohistological studies showed a significant number of T cells infiltrating synovial tissues in the chronic stage of joint inflammation (Yoshino, 1994).

Reproductive

    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    SIMETHICONEC
    Reference: Briggs et al, 1994
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) ESOPHAGITIS
    1) Esophageal manometry indicated that six of eight breast-fed children of mothers with silicone breast implants had decreased lower esophageal sphincter pressure and abnormal peristalsis in the distal esophagus.
    a) In contrast, bottle-fed children, whose mothers had silicone breast implants, had manometric findings similar to those of control children, whose mothers had no silicone breast implants, and distinct from those of the breast-fed children whose mothers had silicone breast implants (Levine and Ilowite, 1994).
    B) IMMUNE DISORDER
    1) In an unpublished study, children of women who have had silicone breast implants have had intestinal complaints and other symptoms of unusual immune disorders (Levine, 1993). A group of 11 children who had been breast-fed by mothers with silicone breast implants had chronic esophageal dysmotility, which can be a sign of scleroderma (Levine et al, 1996). None of the mothers or the children met diagnostic criteria for scleroderma, however (Levine & Ilowite, 1996).
    C) LACK OF EFFECT
    1) Children born to mothers with silicone breast implants did not differ in autoantibody prevalence from controls (Levine et al, 1996).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Two large studies have not found an increase in cancer among patients with silicone breast implants.
    3.21.3) HUMAN STUDIES
    A) LACK OF EFFECT
    1) Several large studies have not found an increase in cancer among patients with silicone breast implants (Petit et al, 1994; Duffy & Woods, 1994) Conger et al, 1993).
    2) To date, there is no proof that silicone breast implants can cause breast cancer (Park et al, 1993). No studies have been published which implicate silicone breast implants in breast cancer, and breast cancers in women with and without silicone implants do not differ in their characteristics (Edelman et al, 1995).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Some silicones have caused tumors when injected under the skin in experimental animals, but this route is not pertinent for human occupational exposure (Clayton & Clayton, 1994).

Genotoxicity

    A) At the time of this review, no genetic studies were found for silicone.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Routine laboratory studies are generally not needed.
    B) Obtain a chest x-ray in patients with pulmonary symptoms.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Mean plasma silicon levels were 0.275 +/- 0.022 mcg/mL (mean +/-SE) in normal subjects 0.48 +/- 0.085 mcg/mL in patients with chronic renal failure, and 0.839 +/- 0.057 mcg/mL in patients undergoing regular dialysis (Berlyne et al, 1985).
    2) Abnormal liver function tests have been seen in those who had silicone migrated to the liver with subsequent hepatitis (Ellenbogen et al, 1975).
    4.1.4) OTHER
    A) OTHER
    1) ULTRASOUND
    a) Ultrasound findings of implant wall redundancy, combined with abnormal silicone echogenicity, correlate well with predicted and surgically-confirmed rupture of silicone breast implants (Petro et al, 1994).

Radiographic Studies

    A) CHEST RADIOGRAPHY
    1) Obtain a chest x-ray in all symptomatic patients following intentional subcutaneous exposure to silicone fluid.
    a) Evidence of bilateral opacities has been observed in patients that have developed silicone-induced pulmonary embolism (Restrepo et al, 2009).
    B) CHEST COMPUTED TOMOGRAPHY
    1) Obtain a chest computed tomography (CT) in patients that demonstrate respiratory symptoms (i.e., dyspnea, acute respiratory distress) following intentional exposure to subcutaneous silicone fluid.
    a) In a study of 10 patients with silicone-induced pulmonary embolism, plain films and chest CT findings consistently demonstrated consolidation (n=7) and bilateral peripherally distributed ground-glass opacities along with interlobular septal thickening in all 10 patients. Several risk factors for the development of silicone pulmonary embolism included the use of high volumes of silicone fluid (up to 1 liter) and manipulation of the skin following the injection(s). Common sites of silicone fluid injection have included the gluteal and trochanteric regions, as well as the pectoralis muscles and arms (Restrepo et al, 2009).

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Plasma silicon can be measured using atomic absorption photometry using the carbon (flameless) furnace (Berlyne & Caruso, 1983).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Routine laboratory studies are generally not needed.
    B) Obtain a chest x-ray in patients with pulmonary symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not indicated.
    6.5.2) PREVENTION OF ABSORPTION
    A) Decontamination is not indicated. Surgical excision may be considered for severe tissue reactions to injected silicone.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Overdose treatment is symptomatic and supportive.
    B) MONITORING OF PATIENT
    1) Routine laboratory studies are generally not needed.
    2) Obtain chest radiographs in patients with pulmonary symptoms.

Inhalation Exposure

    6.7.2) TREATMENT
    A) SUPPORT
    1) Inhalation hazard is low due to the low vapor pressure of most silicone fluids. Treatment is symptomatic and supportive.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) Polydimethylsiloxane: A typical case presents 24 hours after silicone injection with high fever, thoracic aches and dyspnea followed by respiratory failure (Chastre et al, 1983).

Range Of Toxicity

Minimum Lethal Exposure

    A) ORAL EXPOSURE
    1) Silicones have a very low oral toxicity. Several rat studies have shown no or minimal toxicity even when given chronic doses in their diets (Stokinger, 1981).
    B) SUBCUTANEOUS EXPOSURE
    1) CASE SERIES: In a retrospective review of 10 patients with silicone-induced pulmonary embolism, all 10 patients presented with acute respiratory distress along with fever in 5 cases. The cases included 8 men (6 male-to-female transsexuals) and 2 women who intentionally injected massive amounts of a highly viscous agent purportedly containing a silicone oil. Severe respiratory insufficiency requiring intubation and mechanical ventilation occurred in 6 patients, with 2 fatalities reported (Restrepo et al, 2009).
    2) CASE REPORT: A 45-year-old transsexual man with a history of HIV developed multi-system organ failure after multiple subcutaneous silicone injections (total volume 1 to 2 liters) due to embolization of the lungs, brain and heart. Within several hours of injections, the patient developed difficulty breathing and was lethargic but arousable. Within 2 hours of admission, pulmonary function rapidly deteriorated requiring intubation and the patient became obtunded. Despite mechanical ventilation, hypoxia continued with no change in neurologic function. Several CT scans of the brain showed mild edema, but no other focal findings. By day 22 in consultation with the family, mechanical ventilation was stopped and the patient died that day. Autopsy demonstrated pneumonia, ARDS, and foreign body giant cells reactions to round optically clear material in the lungs and in the heart, massive amounts of silicone were found in the hips and buttocks region (Clark et al, 2008).

Maximum Tolerated Exposure

    A) In a retrospective review of 10 patients with silicone-induced pulmonary embolism, all 10 patients presented with acute respiratory distress along with fever in 5 cases. The cases included 8 men (6 male-to-female transsexuals) and 2 women who intentionally injected massive amounts of a highly viscous agent purportedly containing a silicone oil. Severe respiratory insufficiency requiring intubation and mechanical ventilation occurred in 6 patients, with 2 fatalities reported. The onset of respiratory symptoms following subcutaneous silicone injection was highly variable (i.e., 15 minutes up to 2 days). Alveolar hemorrhage was confirmed in all 6 patients that underwent bronchoalveolar lavage or transbronchial biopsy. Chest CT findings consistently demonstrated consolidation (n=7) and bilateral peripherally distributed ground-glass opacities along with interlobular septal thickening in all 10 patients. Several risk factors for the development of silicone pulmonary embolism included the use of high volumes of silicone fluid (up to 1 liter) and manipulation of the skin following the injection (Restrepo et al, 2009).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Plasma silicon levels in normal subjects were 0.275 +/- 0.022 micrograms/milliliter (mean +/- SE) (Berlyne et al, 1985).

Summary

    A) TOXIC DOSE: Ingestion does not cause systemic toxicity, although packets may cause foreign body effects. Most cases of severe toxicity are associated with injection of large volumes of silicone oil.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) SIMETHICONE -
    a) GAS RETENTION - The usual oral adult dose of SIMETHICONE for GAS is 40 to 125 milligrams four times a day, either as a chewable tablet or capsule, administered after each meal and at bedtime (Prod Info Gas-X(R), simethicone, 1995) Prod Info Mylanta(R) Gas, 1995).
    b) ULTRASOUND IMAGING - The recommended dose of a suspension containing 7.5 milligrams/milliliter (mg/mL) simethicone-coated cellulose is 400 mL administered orally over 15 minutes. The patient should fast at least 4 hours before taking the suspension (Prod Info SonoRx(R), simethicone coated cellulose suspension, 1998).
    c) MAXIMUM DOSE - The maximum daily dose of SIMETHICONE should be limited to 480 or 500 milligrams, depending upon the formulation used (Prod Info Gas-X(R), simethicone, 1995) Prod Info Mylanta(R) Gas, 1995).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) ORAL
    a) SIMETHICONE - The pediatric dose may be administered via drops. To relieve the painful symptoms of excess gas in the gastrointestinal system, the usual recommended simethicone dose for children over 2 years of age is 0.6 milliliter (40 milligrams) 4 times daily after meals and at bedtime. For infants or children under 2 years, the usual dose is 0.3 milliliter (20 milligrams) 4 times a day administered after meals and at bedtime (Prod Info Mylicon Infants' Drops(R), 1997).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) DIMETHYL SILOXANE
    B) METHYLPOLYSILOXANE

Physicochemical

Physical Characteristics

    A) Silicones are chains of alternating silicone and oxygen atoms which have various organic groups added. The amount of cross-linkage determines whether the polymer is solid, an elastomer, or fluid (Finkel, 1983).

Molecular Weight

    A) Varies

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Dogs developed hemiplegia, skew deviation of the eyes, generalized ataxia, apathy, and apparent blindness shortly after beginning an investigation of long-term extracorporeal perfusion. Methylpolysiloxane, an antifoaming agent used in the bubble-dispersion-type oxygenator to perform perfusion was found to produce changes consistent with the above findings (Reed & Kittle, 1959).

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