You are on page 1of 9

Further to the recent publication of Volume 2: Appendices of the Poly Implant Prothse

(PIP) breast implants: nal report of the Expert Group Sir Bruce Keogh, NHS Medical
Director.
1
(version 1 February 2013 with corrections to small errors in Table 1 and 2.
This version supersedes the appendices published on 18 June 2012).
http://www.dh.gov.uk/health/les/2012/06/PIP-expert-group-report-appendices.pdf
We have the following concerns.
In particular we draw attention to:
The second of two questions: at 2. Volume 2: Appendices
Does PIP silicone have potential health hazards not associated with medical grade
silicone?
If it has been assumed for the purposes of the Expert Group report that medical grade
silicones have potential health hazards, as indicated at Volume 2: Appendices 2.ii What are
the potential health hazards of medical grade silicones in this case? Clarication
necessary.
Volume 2: Appendices 5. i
There was no evidence in any silicone for any signicant organic impurities.
FALSE: See GC-MS data in LGA report. In all reports of analysis are cited several
substances which are not directly associated to polydimethylsiloxanes: for instance,
besides different silylated organic compounds, there are also other chemical substances of
which one in all PIP batches have been identied, CAS number 000465-65-6 common
name NALOXONE, a pharmaceutical drug.
.
Volume 2: Appendices 5. iii
There were no other differences between PIP silicone and medical grade silicone.
No evidence of further investigations into other differences
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
1
Volume 2: Appendices 5.vii

A low level of caesium (0.3 ppm) was found in PIP silicone, but not in medical grade
silicone
http://www.atsdr.cdc.gov/toxproles/tp157.pdf
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency
for Toxic Substances and Disease Registry April 2004 : suggests there are simply 'no data'
on many of the relevant issues of potential toxicity of Cs in the human body.
Concerns about Cs merit further examination.

Platinum levels were found to be lower in PIP silicone (0.1ppm) than in medical grade
silicone (3ppm).
Platinum is necessary as essential component of the catalyst used for the
synthesis polydimethylsiloxanes in the presence of proper cross linkers to yield cohesive
silicone gel. For this reason it is always found at trace levels in the
nal silicone gel. The lower concentration of platinum in PIP can be a clue indicating
the fact that PIP silicone has not been manufactured using the proper technological
procedure. New evidence shows it is not cohesive gel.
Volume 2: Appendices 6.
The important conclusions that can be drawn from this are:
PIP batches do not display batch to batch variation with respect to chemical
composition
The only potentially biologically relevant differences between PIP silicone and medical
grade silicone is that in the former there are increased levels of siloxanes.
It is of concern that immediate quantitative determination of these contaminants has
not been undertaken.
These data are consistent with comparable analyses conducted by the French regulatory
authority Agence Francaise de Scurit Sanitaire des Produits de Sant (AFSSAPS, now
the Agence Nationale de Scurit du Medicament, ANSM), and by the Australian
regulatory authority the Therapeutic Goods Administration (TGA).
All referenced authorities conducted analysis and failed to report the presence of D10-
D21 silicones, the main silicones present in PIP.
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
2
Toxicity Testing of PIP Silicone
Volume 2: Appendices 7. Genotoxicity - tested on bacterium
Volume 2: Appendices 7 Cytotoxicity - negative results: tested on cells from a mouse
embryo, here considered relevant to the cytotoxicity of silicones in humans
Volume 2: Appendices 8 Our view currently is that there is no potential for skin irritation.
(216921) At paragraph 8.1 indicates the laboratory itself admits the determinations were
carried out in conditions beyond acceptance criteria. Therefore, these deviations from
protocol should have been considered to have affected the integrity of outcome of the
study.
Volume 2: Appendices 9
Toxicity of siloxanes general considerations
9. Against the background summarised above, attention now focuses on the potential
toxicity of siloxanes, and whether their increased concentrations in PIP implant silicone
represents a health risk. The most common, and the most thoroughly investigated,
siloxanes are:
Octamethylcyclotetrasiloxane (D4)
Decamethylcyclopentasiloxane (D5)
Dodecamethylcyclohexasiloxane (D6)
The results appear to have omitted the identication of the silicone series from D10
to D21.
Volume 2: Appendices 10
Siloxanes are used in a wide variety of applications, including: sealants, paints, cosmetics
and personal care products, waxes and polishes, textiles, paper coatings, mechanical
uids and others. Such exposures collectively may lead to detectable levels of siloxanes in
the body.
The main uses of D4 can be divided into four areas:
Use as a site-limited chemical intermediate at the site of production.
Use as an off-site chemical intermediate.
Use in personal care products (e.g. cosmetic, skin- and hair-care products).
Use in household products (e.g. cleaning products).
http://echa.europa.eu/documents/10162/19d40ef0-a0d2-4e93-8840-ae1e1572e5ca
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
3
Thus, in 2005 results from Swedish National Screening Programme were published by the
Swedish Environmental Research Institute. As part of that survey which focused on
siloxanes, breast milk samples from 49 unselected and unidentied women were
analysed. Eleven of those 49 samples were found to contain detectable levels of one or
more of D4, D5 and D6.
Data in the referenced study nd environmental toxins have been detected in a signicant
number of women (11 out of 49) in a study on breast milk. The study does not
extrapolate data to include details of any health effects of these toxins in babies and
very young children. This is of particular concern to all women exposed to higher
concentrations of D4 - D21 and should be of some considerable concern to the SCCP and
ECHA.
Particularly as no further decision on the properties and possible follow-up under REACH
has been taken yet:
With the transition from the now repealed Council Regulation (EEC) No 793/93 to the
REACH Regulation (Regulation (EC) No 1907/2006, the UK competent authorities were
nominated by ECHA to evaluate the substance. Based on the available information, the
UK proposed that D4 could meet the Annex XIII criteria for both a !persistent,
bioaccummulative and toxic" (PBT) and a !very persistent and very bioaccumulative
(vPvB) substance in the environment.
2
D4 PBT/vPvB Evaluation
3.1 Classication in Annex I of Directive 67/548/EEC
Human health Repro. Cat 3 R62: Possible risk of impaired fertility.
3.2 Classication in Annex VI of Regulation (EC) No. 1272/2008 Environment
Human health Hazard class and category: Repr. 2. Hazard statement: H361f:
Suspected of damaging fertility.
http://echa.europa.eu/documents/10162/19d40ef0-a0d2-4e93-8840-ae1e1572e5ca
Volume 2: Appendices 11 One issue that needs to be addressed derives from a review of D4
by the SCCP (Scientic Committee on Consumer Products) dated 2005
In that review it was reported that inhalation exposure of rats to D4 was associated with
delayed ovulation associated with reduced fertility. The NOAEL was judged to be 300ppm
by inhalation. On that basis siloxane D4 is identied under the CLP (Classication,
Labelling and Packaging) regulations as having adverse effects on fertility.
Here SCCP results obtained in vivo in rats are considered relevant to humans under
CLP regulations.
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
4
Volume 2: Appendices 12 Although D4 shows very weak estrogenic activity in a rat
uterotrophic assay, the reproductive toxicity observed is believed not to be attributable to a
direct estrogen receptor (ER)-mediated effect. Rather it is proposed that the effects seen
are due to D4 causing a delay or blockage of the luteinising hormone surge that is
required for optimal timing of ovulation. The opinion of the SCCP is as follows: It can be
concluded that the reproductive effects of D4 in female rats and mice are related to rodent
specic imbalance in the normal hormone milieu. Such imbalances are common in rodents
and are of little relevance to humans.
Concerns are raised by results obtained in vivo in rats, here considered not relevant to
humans, while those regarding cytotoxicity and genotoxicity, obtained working in vitro on
bacteria and mice cells respectively are previously given as evidence for safety in humans.
Volume 2: Appendices 13. Moreover, 2010 the Scientic Committee for Consumer Safety
(SCCS) published this opinion:
The SCCS is of the opinion that cyclomethicone (D4, D5) does not pose a risk for human
health when used in cosmetics
Cosmetics should not to be confused with cosmetic surgery or High Risk Category III,
Implantable Medical Devices.
Volume 2: Appendices 14 Siloxanes risk assessment
To date the only hazard of potential concern has been evidence from rodent studies of
effects on female fertility. However, the opinion of the SCCP was that this does not
represent a risk to human health.
The opinion of the SCCP relates specically to D4
3
and D5 in Cosmetics/Personal care
products. The hazard of potential concern remains evidence from rodent studies of
effects of D4 on female fertility in women affected by PIP breast implants.
Volume 2: Appendices 15 It is nevertheless appropriate to consider the concentrations of
siloxanes D4, D5 and D6 in PIP implants, and in medical grade implants, should formal
risk assessments be required in the light of emerging data.
There are no MHRA/DoH studies involving women and children affected. No British
health data concerning ruptures or rupture rate, gel bleeds, lymphadenopathy or ALCL
(Anaplastic Large Cell Lympoma).
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
5
Volume 2: Appendices 16 Currently it is uncertain whether LGC will be able to supply
information on the concentrations of siloxanes in the batches of PIP and medical grade
silicone that they have analysed (summarised above). In the absence of those data it is
necessary to rely on the results of analyses conducted and reported by TGA.
In the MHRA view, the presence of siloxanes are the main difference between PIP and
medical grade silicones therefore, it is established as a critical point. It is of concern that
the small additional effort needed to quantify them has not been performed. There is no
extrapolation from the other experiments: on irritation or genotoxicity.
Volume 2: Appendices 18 No similar data are available regarding the concentrations of
siloxanes found within medical grade implant silicone. However, AFSSAPS has reported
that NUSIL silicone contained less than 50ppm low molecular mass silicones.
Table 3. Volatile Results
Compound Shell Not Exposed Shell Exposed Gel Filler Whole Device
to Gel (ppm) to Gel (ppm) (ppm) (ppm)
D3 ND 0.19 0.18 0.18
D4 <0.06 0.23 0.49 0.46
D5 0.28 0.79 1.60 1.47
Methoxytrimethylsilane 3.13 3.34 ND 0.43
Dimethoxydimethylsilane ND 0.20 ND 0.03
Methoxytriethoxysilane 0.04 ND ND ND
Table 4. Semi-Volatile Data
Compound Shell Not Exposed Gel Filler to Gel Shell Exposed Whole Device to Gel
(g/g) (g/g) (g/g) (g/g)
Cyclic Dimethyl Siloxanes
D4 ND 0.5 ND 0.5
D5 ND 2.5 <2.5 <2.5
D6 ND 4.9 <4.2 <4.8
Excerpts from: SUMMARY OF SAFETY AND EFFECTIVENESS DATA
Silicone Gel-Filled Breast Implants
Mentor MemoryGel Silicone Gel- Filled Breast Implants
Mentor Corporation 201 Mentor Drive Santa Barbara, California 93111
P030053 April 13, 2005 November 17, 2006
PMA P030053: FDA Summary of Safety and Effectiveness Data
4
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
6
Volume 2: Appendices 19 iii PIP silicone does not contain any major organic or inorganic
impurities
False
See: 5 i above.
In all reports of analysis are cited several substances which are not directly associated to
polydimethylsiloxanes. See GC-MS data in LGA report.
Volume 2: Appendices 19 vi Siloxane D4 has been found to cause reduced female fertility in
rats following inhalation exposure to concentrations of 300ppm or greater. However, this is
not regarded as representing a risk to human health.
Arbitrary Conclusion
Volume 2: Appendices 19 vii PIP breast implant silicone differs from medical grade silicone
only with respect to an increased concentration of siloxanes
False: Very serious concerns are yet to be addressed specically relating to low
viscosity and elasticity and no testing of the Polymeric Silicone Fraction.
Additional concerns:
-----------------------------
(216921) Model relevance
(216922) Appears to be missing
(216924) 1. Appears to be a re-edition of the former version dated April 2012. There does
not appear to be any additions or changes but many of the substances identications
are still wrong.
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
7
Additional grave concerns:
--------------------------------------
Breast Feeding mothers with ruptured PIP implants
(216925) 2. Results appear to point to no transfer of silicones into milk.
The calibration method used is a silicone-containing substance (formula: (NH4)2SiF6) ).
This is a stable and non volatile inorganic salt, while the subject of the analysis is a mixture
of organic-like substances. They may totally evaporate before 280C (in their sample
preparation they reach 1000C in a open platinum crucible). So we are unsure why a
silicone oil (the most obvious option to an analytical chemist) was not used as control
substance (alone and added to cows milk), to make sure there is no loss of silicones
during sample heating.
Case results from just one sample with no information about the condition of the
prostheses (intact/ ruptured / bleeding) have little relevance.
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
8
Independent Late Submission: PIP ACTION CAMPAIGN
PIP VICTIMS & ETHICAL PROFESSIONALS (International)
6 February 2013
SCENIHR
9
1
Volume 2: Appendices of the Poly Implant Prothse (PIP) breast implants: nal report of the Expert Group
Sir Bruce Keogh, NHS Medical Director.
(updated 1 February 2013 to reect corrections made to small errors in Table 1 and 2.
This version supersedes the appendices published on 18 June 2012).
http://www.dh.gov.uk/health/les/2012/06/PIP-expert-group-report-appendices.pdf
http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con216924.pdf
http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con216925.pdf
http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con216926.pdf
http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con216923.pdf
http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con216921.pdf
2
Correspondence: 8 January 2013 European Commission Ref: ENTR/F2/RS/sik Ares (2013)
Classication of the substance Octamethylcyclotetrasiloxane (D4)
Signed by: Klaus Berend Head of Unit F2 DG ENTR, Sabine Lecrenier Head of Unit B2 DG Sanco, Bjorn
Hansen Head of Unit D3 DG ENV
3
Cyclotetrasiloxane, octamethyl- (Siloxane D4) in Industrial Efuents
Pollution Prevention Planning Notice
Notice Requiring the Preparation and Implementation of Pollution Prevention Plans in Respect of
Cyclotetrasiloxane, octamethyl- (Siloxane D4) in Industrial Efuents
On June 2, 2012, the Minister of Environment published a notice under Part 4 of the Canadian
Environmental Protection Act, 1999 (CEPA 1999) requiring the preparation and implementation of Pollution
Prevention Plans in respect of D4 in industrial efuents. This notice applies to any person who owns or
operates an industrial facility that manufactures or uses D4 or a mixture containing D4, where the total
quantity of D4 used or manufactured is equal to or greater than 100 kg during a calendar year, and, as a
result of manufacturing or use, the efuent at the nal discharge point(s) of the facility contains D4.
This notice outlines the requirements to prepare and implement pollution prevention plans. The schedules to
be completed and submitted to the Minister within the required timelines by persons subject to the Notice
have also been included.
Notice Requiring the Preparation and Implementation of Pollution Prevention Plans in Respect of
Cyclotetrasiloxane, octamethyl- (Siloxane D4) in Industrial Efuents (HTML) (PDF; 6.22 MB)
http://www.ec.gc.ca/planp2-p2plan/default.asp?lang=En&n=51567C93-1
4
Excerpts from: SUMMARY OF SAFETY AND EFFECTIVENESS DATA
Silicone Gel-Filled Breast Implants
Mentor MemoryGel Silicone Gel- Filled Breast Implants
Mentor Corporation 201 Mentor Drive Santa Barbara, California 93111
P030053 April 13, 2005 November 17, 2006
PMA P030053: FDA Summary of Safety and Effectiveness Data
http://www.accessdata.fda.gov/cdrh_docs/pdf3/p030053b.pdf

You might also like