Siloxanen

Siloxanen zijn chemische verbindingen met een keten van afwisselend silicium- en zuurstofatomen.

In siliconen implantaten zitten vloeibare vluchtige siloxanen, zoals:

D4 octamethylcyclotetrasiloxaan

D5 decamethylcyclopentasiloxaan

Bij het van de markt halen van de implantaten door de FDA in 1992, werden de hoge dosering van ca 855 parts per million D4 en D5 onveilig genoemd. Bij het weer op de markt brengen van de implantaten in 2006, moest deze hoeveelheid teruggebracht worden tot maximaal 69 ppm. Dat betekent dat vrouwen met implantaten van vóór 2006 langdurig zijn blootgesteld aan veel te hoge dosering D4 en D5.

Volgens onderzoeken zijn de risico’s van D4 en D5:

• Auto-immuunreacties

• Fenobarbitalachtige reacties in lever van ratten

• Zwak oestrogene werking

• Verandering vrouwelijke voortplantingsorganen van ratten

• D4 aangetoond in hersenen, longen, klieren, vetweefsel

• Siloxanen en platina lekken in omliggend weefsel

Cyclic volatile methylsiloxanes in human blood as markers for ruptured silicone gel-filled breast implants 2016

The replacement of medical-grade silicone with industrial-grade silicone material in some silicone gel-filled breast implants (SBI) manufactured by Poly Implant Prothèse and Rofil Medical Nederland B.V., reported in 2010, which resulted in a higher rupture tendency of these SBI, demonstrates the need for non-invasive, sensitive monitoring and screening methods. Therefore a sensitive method based on large volume injection-gas chromatography coupled to mass spectrometry (LVI-GC/MS) was developed to determine octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclo-hexasiloxane (D6) in blood samples from women with intact (n = 13) and ruptured SBI (n = 11). With dichloromethane extraction, sample cooling during preparation, and analysis extraction efficiencies up to 100 % and limits of detection of 0.03-0.05 ng D4-D6/g blood were achieved. Blood samples from women with SBI were investigated. In contrast to women with intact SBI, in blood from women with ruptured SBI higher D4 and D6 concentrations up to 0.57 ng D4/g blood and 0.16 ng D6/g blood were detected. With concentrations above 0.18 D4 ng/blood and 0.10 ng D6/g blood as significant criteria for ruptured SBI, this developed analytical preoperative diagnostic method shows a significant increase of the recognition rate. Finally a higher precision (error rate 17%) than the commonly used clinical diagnostic method, mamma sonography (error rate 46%), was achieved. 

Determination of low moleculair weight silicones in plasma and blood of women after exposure to silicone breast implants by GC/MS 2003

A sensitive, one-step sample preparation method for detection of volatile, low molecular weight (LMW) cyclic silicones hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) in plasma and blood using gas chromatography coupled with mass spectrometry (GC/MS, SIM mode) is presented. In spiked experiments, extraction efficiencies for these siloxanes (100−20 000 ng/mL) were approximately 90% for plasma and approximately 80% for blood; only in the case of D3 was the recovery very low. Plasma and blood of women who are or were exposed to silicone gel-filled implants and of control subjects were analyzed for low molecular weight silicones. D3−D6 were not detectable in control plasma or blood. Although the investigated numbers of patients samples are very limited, and thus, no statistical analysis is possible, our data clearly show a general increase in the amount of LMW cyclic siloxanes in the bodies of women with silicone implants. In particular, several years after ruptured silicone implants were removed, siloxanes could still be found in blood samples from several women. Siloxane compound D3 varied between 6 and 12 ng/mL (plasma) and between 20 and 28 ng/mL (blood), whereas the concentration range of D4 was 14−50 ng/mL (plasma) and 79−92 ng/mL (blood). D5 and D6, with one exception, could not be detected.

Methods for detecting silicones in biological matrixes  

Methods for analyzing for silicon and silicone in biological matrixes were developed. Asilicone-specific technique involved microwave digestion of samples in acid solution to rapidly break down the biological matrix while hydrolyzing silicones to monomeric species. The resulting monomeric silanol species were then capped with trimethylsilyl groups, extracted into hexamethyldisiloxane, and analyzed by gas chromatography. In serum, positive identification of silicone species with detection limits below 0.5 μg of Si/mL are possible with this technique. The technique is compared with a silicone-specific technique,29Si NMR, and a non-silicone-specific technique, ICP-AES. 29Si NMR was far less sensitive, with a detection limit of only 64 μg of Si/mL in serum when analyzing for one compound with a single sharp resonance. Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) has potentially lower detection limits, but the technique is not silicone-specific and suffers from species-dependent responses

Onze vermoedens met betrekking tot de siloxanen worden in onderstaande documenten bevestigd. 

Na de ban in 1992 werden door de EPA en Dow Corning met name 6 siloxanen onderzocht i.v.m. mogelijke toxiciteit en carcinogeniteit. 

Fabrikant Dow Corning over betrekking tot siloxanen D4, D5 en L2 

EPA: Requirements under section 8 d of the toxic substances control act october 15 1996

Guidance for saline, silicone gel and alternative breast implants 

In the FEDERAL REGISTER of June 24, 1988 (53,FR 23856), FDA issued a final ruling classifying the silicone inflatable (saline-filled) breast prosthesis into Class III (21 CFR 878.3530). On January 6, 1989 (54 FR 550), FDA published a notice of intent to require premarket approval. On January 8, 1993 (58 FR 3436), FDA issued a proposed rule requiring a PMA. On August 19, 1999 (64 FR 45155), FDA required a PMA or PDP for these devices to befiled with the Agency within 90 days.

In the FEDERAL REGISTER of June 24,1988 (53 FR 23863), FDA issued a final rule classifying the silicone gel-filled breast prosthesis into class III (21 CFR 878.3540). On January 6, 1989 (54 FR 550), FDA published a notice of intent to require premarket approval. On April. lo,1991 (56 FR 14620), FDA required a PMA for these devices be filed with the Agency within 90 days.

Oostenrijkse overheid over siloxanen  (link werkt niet meer)

In der EU ist bisher nur D4 als gefährlich eingestuft. Die in mehreren Studien nachgewiesenen Effekte weisen darauf hin, dass es möglicherweise die Fortpflanzungsfähigkeit beeinträchtigen aber auch in Gewässern längerfristig schädliche Wirkung haben kann. Einige Studien geben Hinweise auf eine mögliche Schädigung der Leber durch D4 und der Lunge durch D5, andere Studien zeigen eine mögliche Betroffenheit von Lunge und Niere durch L2. Für D5 wird eine möglicherweise krebserzeugende Wirkung angenommen. 

Nog een stukje hieruit : 

Im Rahmen eines so genannten Produkt-Monitorings wurden im März 2010 auch Konsumprodukte im Hinblick auf mögliche Gesundheits-Gefährdung durch Siloxane untersucht. Es wurden verschiedene Alltagsprodukte auf das Vorkommen zyklischer (D4, D5, D6) und linearer Siloxane (L3, L4, L5) getestet: Latex-Einmalhandschuhe, Baby-Schnuller, Sauger einer Baby-Trinkflasche, Anti-Stress-Ball, zwei verschiedene Muffin-Backformen und eine Spülbeckeneinlage. 

Dow Corning Technical Report   

Onderzoek naar D4, D5 en L2 (hexamethyldisiloxane)

Siloxane D5 in drycleaning applications

EPA has received results of a cancer study on Siloxane D5 in rodents, submitted under TSCA section 8(e). The results of this study indicate that there may be a cancer hazard associated with D5. However, the Agency has not conducted a risk assessment for D5, and, therefore, is not in a position to characterize potential risks to human health, or the environment associated with D5 use in drycleaning.

What is Siloxane D5?

Decamethylcyclopentasiloxane, or D5, is an odorless, colorless liquid that has many consumer and industrial applications. D5 is used as an ingredient in a number of personal health and beauty products, including deodorants, antiperspirants, cosmetics, shampoos, and body lotions. It is also used as a drycleaning solvent and in industrial cleaning.

Have other studies been conducted?

The subject cancer study is one of a broad range of toxicological studies on D5 and several other siloxanes that are being conducted voluntarily by the Dow Corning Corporation under a Memorandum of Understanding signed with EPA in 1996.

What are the results of the study?

In February 2003, EPA received from Dow Corning the preliminary results of a two-year chronic toxicity and carcinogenicity study on D5 using rats. In this study, groups of 60 male and 60 female Fischer 344 rats were exposed to vapor concentrations of 0, 10, 40, or 160 ppm of D5 for 6 hours per day, 5 days per week, for 24 months. The preliminary results show that female rats exposed to the highest concentration of D5 exhibited a statistically significant increase of uterine tumors.

In July, 2005 EPA received the final results of the two-year study in rats, which confirmed the significant increase in uterine tumors following exposure to 160 ppm of D5, the highest concentration tested in the study. No significant increase in tumors was observed at lower doses.

How were the result submitted?

Dow Corning submitted the results of their study under section 8(e) of the Toxic Substances Control Act (TSCA). Section 8(e) requires that U.S. chemical manufacturers notify EPA of information that could support a conclusion of substantial risk of injury to health or the environment. Section 8(e) submissions most often contain toxicity data, but may also contain information on exposure, environmental persistence, or actions being taken to reduce human health and environmental risks.

How will EPA follow up?

EPA has received the work agreed upon in the MOU and a Public Docket has been established to make data and information developed through this MOU available to the public. The docket number EPA-HQ-OPPT-2009-0180 can be accessed through http://www.regulations.gov . Docket materials include more than 88 reports assessing potential toxicity and exposure, annual progress reports, science briefings, and related TSCA section 8(e) notices and additional submissions concerning D5 and five other siloxanes that were subject to the MOU.

Office of Pollution Prevention and Toxics (7404)

744-F-03-004

December 2005The subject cancer study is one of a broad range of toxicological studies on D5 and several other siloxanes that are being conducted voluntarily by the Dow Corning Corporation under a Memorandum of Understanding signed with EPA in 1996.

February 2003, EPA received from Dow Corning the preliminary results of a two-year chronic toxicity and carcinogenicity study on D5 using rats. In this study, groups of 60 male and 60 female Fischer 344 rats were exposed to vapor concentrations of 0, 10, 40, or 160 ppm of D5 for 6 hours per day, 5 days per week, for 24 months. The preliminary results show that female rats exposed to the highest concentration of D5 exhibited a statistically significant increase of uterine tumors

In July, 2005 EPA received the final results of the two-year study in rats, which confirmed the significant increase in uterine tumors following exposure to 160 ppm of D5, the highest concentration tested in the study. No significant increase in tumors was observed at lower doses.

EPA has received the work agreed upon in the MOU and a Public Docket has been established to make data and information developed through this MOU available to the public. The docket number EPA-HQ-OPPT-2009-0180 can be accessed through http://www.regulations.gov. Docket materials include more than 88 reports assessing potential toxicity and exposure, annual progress reports, science briefings, and related TSCA section 8(e) notices and additional submissions concerning D5 and five other siloxanes that were subject to the MOU.