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Addendum of September, 2006

CITIZEN PETITION
November 18, 2003


Dockets Management Branch
Food and Drug Administration
Department of Health and Human Services, Rm 1061
5630 Fishers Lane
Rockville, MD. 20852
FAX 301/827-6870

Re: Silicone Gel-filled Breast Implants


The undersigned submits this petition under 21 C.F.R. 10.35 to request
that the Commissioner of the Food and Drug Administration (FDA) delay
approval of any and all Premarket Applications ("PMAs") for silicone
gel-filled breast implants (SGFBIs) until additional valid long-term
scientific data is collected. We request that in accordance to 21
C.F.R. 14.7, the Commissioner expedite the review of this petition and
make a reasonable effort to render a decision before the action
concerned in the petition is finalized. In addition to the conditions
agreed upon by Inamed, we request that the following conditions be
met:

A. Action Requested

1. We request that the FDA require long-term research (age-matched to
core study participants in a control group) regarding symptoms
including, but not limited to, the following: muscle, joint,
neurological (including depression), muscle pain, joint pain, morning
stiffness, fatigue, and generalized pain. This study should be funded
by Inamed but conducted and reviewed by an independent third party.
The third party must be independent of plastic surgeons as well as all
companies manufacturing breast implants.

2. We request that platinum (including valence) testing and
measurements be conducted in connective tissue (scar capsule tissue)
and explants in a retrieval study. Included in this platinum study
would be chemical and metal sensitization studies of women who have
reported leaking or ruptured implants where platinum has been used as
the catalyst in the manufacturing process.

3. We request that the FDA require a breast-milk study using
appropriate measurements of low molecular weight silicone, particulate
debris, heavy metals, and cytokine levels to determine safety of
breast milk from implanted mothers versus controls. This study should
be funded by Inamed but conducted and reviewed by an independent third
party.

4. We request in-vivo and in-vitro testing for biological responses to
silicone elastomer particles, less than 10 micrometers in size. This
testing is needed to determine a cellular response to particulate
debris in a retrieval study, which should include monocyte, macrophage
and fibroblast responses.

5. We request that blood be drawn on an annual basis from all women in
the Inamed core study. This blood should be tested for natural killer
cell counts and for inflammatory and anti-inflammatory cytokine
levels. This blood should then be stored for future research.

6. We request that the expected serviceable life of the implant while
in the human body be determined and stated in the informed consent
along with the expected shelf life.

B. Statement of Grounds

• The General and Plastic Surgery Devices Panel of the Medical Devices
Advisory Committee voted 9-6 to approve Inamed's SGFBIs, with
conditions. This panel included four plastic surgeons – one with a
stated conflict of interest – and two breast surgeons. While plastic
surgeons should be included on the panel for their expertise, they
should be excluded from voting, as they or their colleagues will
financially benefit if the device is approved.

• One member of the panel stated she decided to vote for approval
after she heard Inamed's summation, proposal of conditions for
approval, and commitment to follow-up. Unfortunately, the best
predictor of future behavior is past behavior. In Inamed's "Adjunct"
study of reconstruction patients barely half stayed in the study for
one year and even fewer (27%) stayed for three years. The revision
patients were even less likely to stay in the study. Less than half
(44%) stayed in the study for one year and only one in five (20%)
stayed for three years. Inamed had only a 57% rate of follow-up for
reconstruction patients after approval of their saline-filled breast
implants was obtained. Their follow-up for augmentation patients was
only 62%. Neither is high enough to assure adequate follow-up at ten
years, as the FDA has required. Manufacturers have shown time and
again that they have no incentive or motivation on follow-up.

• Some members of the panel voiced "shock" that only one, two and
three years of data were provided for consideration. Inamed stated on
October 14, 2003 that the implants under review had been used for ten
years in the U.S. and for twenty-five years in Europe. Even after
this amount of time Inamed still has not been able to provide studies
showing long-term implant safety. This is a red flag and raises
questions of caution and concern.

• In 1992, the FDA announced its decision to allow SGFBIs on the
market only under controlled clinical studies for reconstruction after
mastectomy, correction of congenital deformities, or replacement of
ruptured SGFBIs due to medical or surgical reasons. Until these
clinical studies could be submitted and reviewed, the FDA authorized
temporary and limited distribution of silicone gel-filled implants for
reconstructive patients on an urgent need basis, with a very detailed
informed consent form.

• The FDA denied applications for using SGFBIs for augmentation but
planned that the manufacturers would later conduct clinical trials
that would include a limited number of augmentation patients (the core
studies).

• On July 24, 1992, the FDA approved Mentor Corporation's Stage 2,
Adjunct Study protocol for silicone gel-filled implants for
reconstruction and revision only. A memo (attached as Exhibit A)
dated 9/25/92 from St. John's Regional Health Center, Springfield,
Missouri to the Institutional Review Committee (IRC) members regarding
the "Mentor Adjunct Study of Silicone Gel Breast Implants" makes the
following statements:

"Our subcommittee had a number of concerns about
the design of this study and the consent form. The protocol did
not appear to us to be a ‘research study' in any familiar sense of that
term.

a) There is no accrual goal. The study is simply open for five years
to any women who qualify. Participants are to be followed for five
years.
b) There are few exclusion criteria.
c) Inclusion criteria are very subjective and general.

The consent form omitted a good deal of information that we believed
should be revealed. In one section we found an outright error (when
compared to information given in the protocol itself). Tobias Meeker
called Dr. Grant Bagley of the FDA…Dr. Bagley represented ‘the
clinical point of view' for the FDA team…A National Advisory
Commission (NAC) was formed to review the status of silicone breast
implants. The NAC recommended that a PMA should be required for
marketing of silicone gel- filled breast implants. But the NAC also
states that these devices should continue to be widely available to
persons in unusual circumstances who would have medical need for
them. To this end, the commission recommended that there be a limited
core study that would be quite controlled and an adjunct study that
would make the devices widely available (since not everyone with
medical need – due to location or whatever
– would be able to qualify for a traditional clinical trial.)
The Mentor ‘study' is designed to serve this latter purposes. Dr. Bagley
said of this protocol: ‘It is an administrative device to continue to make these
devices widely available to those who have such need that the lack of
established safety can be over- looked if there is a good informed consent
process and the oversight of an IRC…One of the surgeons who hopes
to do these procedures met with us… His understanding that
this protocol was designed ‘to give the illusion of a study' so that
the devices could remain on the market…We feel that we are being asked to
rubber-stamp a political solution to this highly politicized
issue. This ‘study' will recklessly put many women at risk. Asking
IRCs to behave in this manner violates their mandate and calls into
question their integrity. It appears to us that the FDA has lost
its objectivity."

• On 11/4/92, Tobias Meeker, Director, Ethics Program at St. John's
sent a letter ( Exhibit B) to David Kessler, M.D., Director,
FDA expressing his concerns regarding Mentor's adjunct study. He
reiterates many of his grave concerns expressed in the above memo
including the following:

"A woman could simply report to a surgeon that she didn't
like the appearance of her breasts due to say – ptosis – and medically
‘qualify' to have reconstruction with silicone gel…We realize that many plastic
surgeons have firm convictions that the silicone poses no health risk.
We respect their convictions, but point out that strong convictions do not
constitute scientific evidence…FDA has concluded that women who desire breast
augmentation are at higher risk than patients with breast cancer who
have had a mastectomy

Unlike patients who have undergone mastectomy, they still
have breast tissue and the presence of an implant complicates the use of
mammography for the detection of breast cancer. In the end, it comes down to
this: In our opinion the risk-benefit ratio does not at this time favor the
unrestricted use of silicone breast implants in healthy women. The design of the
Mentor adjunct study belies the concerns you (Dr. Kessler) expressed. This
study makes these devices widely available to women who have not had
mastectomies. If women are to be offered these implants outside of
scientifically valid studies, we believe this offer should be restricted to the present
‘urgent need' population…To assume that a good consent process (with IRC
oversight) will protect subjects from unjustified risks strikes us as a faulty
assumption. This im plant is a product with unproven safety and demonstrated
(but unproven) risks. Further, we are concerned that misrepresenting this
‘administrative device' as a legitimate scientific study misleads potential
recipients, making it more difficult for them to assess risk."

• We believe the same agreement was made with McGhan (now Inamed
Corporation). Many plastic surgeons have built their own outpatient
surgical facilities to circumvent the concerns expressed by the
Institutional Review Committee in the above memo and letter. We
request, as consumers, a more detailed explanation of the FDA's design
and approval of the AR-90 and adjunct study to determine long term
risk in light of the above memo and letter. We request, as consumers,
to know why we do not have ten or more years of data from a well
designed clinical study to determine long term risk for reconstruction
and revision patients. According to Inamed's documents, their 5-year
adjunct study for reconstruction patients started on 11/25/97 and
ended 8/22/02 with a follow-up compliance of 27% at 3 years. We
request, as consumers, to know why the follow-up of the adjunct study
by Inamed had such low compliance rates to thereby, render the data
useless. Consumers can only have true informed consent when they know
the risks they can expect and are willing to accept. Two or three
years of data are inadequate to determine risk for a device that will
be implanted and not removed until suspected of being ruptured.

• When silicone gel-filled devices are implanted into young woman of
childbearing age, they can possibly pass chemicals such as
low-molecular weight silicone, degradation particles, and ionized
platinum to children born after implantation either through the
placental barrier or in breast-milk. Research by Holten et al., 1995
documents a case report (attached as Exhibit C) in which silicone
accumulated in the lactiferous ductal system of the breast with the
underlying prostheses being intact. It demonstrated the disconcerting
potential of silicone to migrate through tissue planes that were not
disrupted. Inamed currently states on their website regarding
breast-feeding and children " A woman with breast implants who has
questions about risks while pregnant or breast feeding should consult
her physician." Until the proper testing is conducted on breast-milk
from implanted women and the long-term clinical studies are completed,
it is impossible for a physician to advise a pregnant woman with
implants on risks.

• Some members of the panel expressed "alarm" that all symptoms
including muscle, joint, neurological, muscle pain, joint pain,
morning stiffness, fatigue, and generalized pain increased after only
two years of implantation. The panel did not have a control group of
age-matched women (other plastic surgery patients without any type of
implant) and in the general population to determine the significance
of this data. Therefore before these devices are approved, we request
a study control group to be evaluated yearly. We request that this
study be funded by Inamed but conducted and reviewed by an independent
third party. Depression should be added to this list of symptoms in
light of three studies indicating a three-fold increased rate of
suicide by breast implanted women – Brinton et al., 2001 (Exhibit D),
Koot et al., 2003 (Exhibit E), and Pukkala et al., 2003 (Exhibit F).

• At the hearings the FDA admitted the issue regarding systemic
disease and mixed connective tissue disease in implanted patients has
still not been resolved.

• In U. S. patent number 6,251,137 (Exhibit G) filed 6/26/01 by McGhan
(now Inamed) it states: "Silicone filled implants typically comprise
about 10-20% cross-linked silicone which forms an interconnected
‘sponge' in the implant with the remainder of the filler material
being low molecular weight silicone oil…adverse medical consequences
have recently become associated with the use of silicone gel filled
implants because it has been discovered that the silicone oil can
migrate through the implant shell and the silicone oil is not
biocompatible with other human tissues". This information presents
grave unknown safety risks.

• In 1999, research from Teuber, et al., (Exhibit H) states: "Silicone
gel once it leaves the implant is not biologically inert and in some
persons can elicit profound pathogenic responses…an unexplained change
in the chemical composition of the implanted silicone gel, rendering
it more fluid-like, may have increased its propensity to migrate
locally. Unfortunately, little research has been performed on
biodegradation of silicone in the body, although there is evidence
that this may occur…the implants and extractable gel/fluid were sent
to the manufacturer (McGhan Medical Corporation, Santa Barbara, CA,
USA) for analysis, but no information is available on the results of
the analysis to determine if the ratio of polymer chain length had
shifted…the relentless inflammatory response against widespread
silicone has already resulted in the near total loss of function of
the hand…no doubt can remain that silicone can induce severe,
devastating local inflammation. " Breast implant manufacturers have
known since 1978 about potential migration of silicone gel when
research reported by Capozzi et al., (Exhibit I) documented that thin
gel had migrated through subcutaneous planes as far as the groin from
a ruptured breast implant.

• Inamed reported 30 days after implantation, 0.06% of radio labeled
gel left the implant site. At the hearing, one of the members of the
panel made the observation that Inamed reported in their retrieval
collections none of the implants lost more than 5 grams of material.
The member of the panel stated: " In orthopedics, a half a gram
would cause osteolysis in the same time period, so 5 grams is actually
a ‘whopping' amount of material." He further stated: "If you had 5
grams distributed kind of uniformly rather than in a lump, it possibly
could be missed in visual observation by the explanting surgeon." In
orthopedics and joint replacement, the most biologically active
particles are ones that cannot be seen visually. Since 1995 the scope
of wear-related problems in orthopedics has expanded to include not
only the local effects of debris but also systemic distribution and
effects, as reported in the book "Implant Wear: in Total Joint
Replacement". According to the authors, both implants and the wear
debris they generate are thought to release chemically active metal
ions. The inflammatory response to metallic and polymeric debris in
lymph nodes has been found to include immune activation of macrophages
and associated production of cytokines. Before approval of this
device, consumers need to know how much gel can be predicted to leave
the implant site after ten or more years of implantation or after
rupture. Sam Arepalli, PhD., FDA Chemist, stated that even with a
barrier layer you could not completely eliminate bleed of the gel from
an implant. There is presently no way to remove the gel, particle
debris, and platinum after it has spread to all parts of the body.

• One of the members of the panel expressed his concern that there
seemed to be a disconnect between Inamed's testing showing how
difficult it was to rupture a new implant and what actually happens in
the body. This disconnect could be explained by 1998 research by
Adams, et al, (Exhibit J) which found: "Ninety-eight percent of
implants and other previously implanted silicone devices were found to
have evidence of lipid infiltration…We conclude that lipids infiltrate
the outer silicone shell and may be a factor related to breast implant
aging and rupture due to progressive mechanical weakening of the outer
silicone shell." This disconnect might also be explained by the 1995
research by Tang, et al., (Exhibit K) which made the following
conclusion: "Chronic inflammatory processes, in many cases in
response to fragments of implanted biomaterials, may cause implant
failure…In some instances, material-mediated inflammatory responses
may even cause degradation of the material itself (via oxidative
products released by implant-associated inflammatory cells)." Before
approval is given, Inamed should be required to conduct testing on
explanted devices to determine if lipid infiltrates have weakened the
shell strength, if chronic inflammatory processes have caused
degradation of the material, or determine a logical explanation of
rupture rates.

• We, as consumers, do not detect any real progress and request the
FDA to inform us on the status of the research as recommended by the
Institute Of Medicine (IOM) after a review of the safety of silicone
breast implants in 1999. The IOM made the following recommendations:

1. "Reliable techniques for the measuring of silicone concentration in
body fluids and tissues are needed to provide established, agreed-upon
values and ranges of silicone concentrations in body fluids and
tissues with or without exposure to silicone from an implanted medical
device. Such developments could improve the study of silicones and
silicone distribution in humans, could help with regulatory
requirements, and might in some circumstances resolve questions by
providing quantitative data on the presence or absence of silicones.

2. Ongoing surveillance or recipients of silicone breast implants
should be carried out for representative groups of women, including
long-term outcomes and local complications, with attention to, or
definition of the following:

• Implant physical and chemical characteristics,
• Tracking identified individual implants,
• Using appropriate, standardized, and validated technologies for
detecting and defining outcomes,
• Carrying out associated toxicology studies by standards consistent
with accepted toxicological standards for other devices; and
• Ensuring representative samples, appropriate controls and
randomization in any specific studies, as required by good
experimental design.

3. The development of a national model of informed consent for women
undergoing
breast implantation should be encouraged, and the continuing
effectiveness of such
a model should be monitored"

• The FDA guidance document (Exhibit L) makes the following statement:
"…for the metal used as the catalyst in the curing reaction, you
should provide the valence state and the amount of residue of the
catalyst." We request an explanation as to why the valence state of
the platinum catalyst at the time of manufacture was not provided by
Inamed. Dow notified the EPA (Exhibit M) on 12/27/96 of substantial
risk to their 3-8015 Intermediate Platinum #2 used as a catalyst in
making breast implants. This notification was the result of skin
sensitization studies. Please advise if Inamed uses Dow 3-8015
Intermediate Platinum #2 as a catalyst in making the breast implants
under current review. If not, please explain in detail the catalyst
used and the safety data provided, as no published research is
available.

• Recent German research by Flassbeck, et al, 2003 (Exhibit N)
"Determination of Siloxanes, Silicon, and Platinum in Tissues of Women
with Silicone Gel-filled Implants" demonstrates that for the first
time in published research, platinum leaks from intact prostheses and
accumulates in a lipid-rich medium analogous to fat tissue or fibrous
tissue in humans. Further this research clearly demonstrates elevated
levels of the siloxanes D4-D6 in fatty tissue of a woman with a
"bleeding" implant. The data from this work clearly show that the use
of elemental silicon as an indicator of migration from breast implants
to the surrounding tissue is not appropriate. In the FDA's letter
(Exhibit O) dated 3/30/01 in response to my petition (Docket Number
00P-16-7/CP-1 Exhibit P) it quoted from the IOM's review of the
potential toxicity of silicon and stated: "…there is ample evidence
that infants breast-fed by mothers with silicone breast implants
receive no higher silicon intakes than infants breast-fed by mothers
without breast implants. Infants receiving cow's milk or commercial
infant formula feedings are likely to have higher silicon intakes than
breast-fed infants." The independent research by Flassbeck
demonstrates that the Dow funded, Semple, et al., 1998 (Exhibit Q)
study of elemental silicon is not an appropriate measurement to
determine safety of breast-milk from implanted mothers.

• In the FDA's letter to CANDO dated 3/30/01 it stated: "The supplier
of the platinum catalyst used to manufacture breast implants, and
scientist who have studied the chemistry of these catalyst, have
recently assured the FDA that chloroplatinic acid is consumed during
the formation of these catalysts and is not present in the materials
used to produce the implants." Inamed's data of metal analysis found
the following: Shell Pt (3.3 PPM), Patch Pt (2.6 PPM), and Gel (4
PPM). With the Flassbeck research (2003) data showing platinum
accumulating in human tissues, with the Maharaj research data showing
significant platinum found in connective tissue of implanted women,
and with the data presented to the FDA (Exhibit R) from Ernest
Lykissa, Ph.D. suggestive that ionic platinum in various oxidation
states may be present in explanted devices, it becomes imperative that
the FDA require Inamed to quantify the amount of platinum and the
valence state in explants, fluids, and tissues in a retrieval study.
Platinum is listed as a suspected respitory, neurological, immune, and
organ toxicant. Chloroplatinic acid is one of the most
hypersensitizing agents known to man. Before approval is given for
implantation of young women of childbearing age, Inamed and the FDA
should determine if the platinum used in breast implants reverts back
to its original form, at any time, after implantation.

• Naidu, et al., (Exhibit S) in 1996 research concluded that an acute
in vivo inflammatory response to silicone elastomer particulate debris
is particle-type specific and that silicone elastomer particles are
acutely inflammatory. Because of concern over well documented
"particle disease or chronic inflammatory syndrome" the following
questions need to be answered before approval is given:

1. How does silicone elastomer and gel age and degrade inside the
body?
2. How does the chemical composition of the shell or gel change during
any stage of the degradation process?
3. What size and how many elastomer particles can be generated inside
the body in five or ten years?
4. Does absorption of silicone fluid and body fats by the elastomer
shell weaken and accelerate degradation and breakdown of the elastomer
shell?
5. Can these particles further physically degrade into smaller and
more reactive particles inside the body?
6. Can monocytes, macrophages and fibroblasts become activated, inside
the body, when they ingest silicone elastomer particles and/or
silicone fluid or gel droplets from silicone gel-filled breast implant
and their shells?
7. Can macrophages synthesize and release inflammatory and
anti-inflammatory cytokines, inside the body, after they ingest
silicone elastomer from the implant shell?

• The FDA stated that the finding of excesses of cancer including lung
(or respiratory), cervical, vulvar, and leukemia in implanted women
have been reported in more than one study. Inamed currently states on
their website under cancer risks "At this time, there is no scientific
evidence that women with silicone breast implants are more susceptible
to cancer than other women." We believe this is inaccurate and
misleading.

• Inamed reported a diagnosed rupture rate of 4.7% for breast cancer
reconstruction patients, 2.2% for revision patients, and 1% for
augmentation patients. The FDA assumed the rupture rate was higher
than reported, since most of the data was based on the first MRI
screening at 1 year and only 29% of the core group had an MRI.
Augmentation and revision patients may lose all of their natural
breast tissue if silicone from ruptured implants has to be scraped out
of the tissues as reported by Vanessa Rose Ferrelli (Exhibit T) at the
hearings. This presents an unacceptable outcome with high patient
dissatisfaction.

C. Conclusion

For the above stated reasons, the Commissioner should delay the
approval of any and all PMA's for SGFBIs until rupture rates and
long-term risk has been ascertained and the conditions stated above
have been met.

D. Environmental Impact

This petition qualifies for categorical exemption under 21 C.F.R.
25.15, 25.30-32 from the preparation of an environmental assessment.

E. Economic Impact

A statement of the economic effect of the petition will be submitted
if deemed necessary by the Commissioner.

F. Certification

The undersigned certifies that, to the best knowledge and belief of
the undersigned, this petition includes all information and views on
which the petition relies, and that it includes representative data
and information known to the petitioner that are unfavorable to the
petition.


Marlene Keeling, President
Chemically Associated Neurological Disorders
P. O. Box 682633
Houston, Texas 77268-2633
281/444-0662
281/444-5468 FAX
keeling.m@att.net


Exhibits

Exhibit A:
Memo from St. John's Regional Health Center, Springfield, Missouri to
the Institutional Review Committee (IRC) members regarding the "Mentor
Adjunct Study of Silicone Gel Breast Implants".

Exhibit B:

Letter dated 11-4-92 to David Kessler, M.D. Director, FDA from Tobias
Meeker, Director, Ethics Program at St. John's Regional Health Center,
Springfield, Missouri

Exhibit C:

Holten, IW, Barnett, RA. Intraductal Migration of Silicone from
Intact Gel Breast Prostheses. Plast Reconstr Surg 1995 Mar; 95 (3):
563-6 PMID 7870784

Exhibit D:

Brinton, LA, Lubin, JH, Burich, MC, Colton, T, Hoover, RN. Mortality
among Augmentation Mammoplasty Patients. Epidemiology 2001;12:
321-326

Exhibit E:

Koot, VCM, Peeters, PHM, Granath, DE, Nyren, O. Total and cause
specific mortality among Swedish women with cosmetic breast implants:
prospective study. BMJ 2993; 326: 527-8

Exhibit F:

Pukkala, E, Kulmala, I, Hovi, SL, Hemminki, E, Keskimaki, I, Lipworth,
L, Buice, JD, McLaughlin, JK. Causes of Death Among Finnish Women with
Cosmetic Breast Implants, 1971-2001. Ann Plast Surg 2003;51: 339-342

Exhibit G:

U. S. Patent number 6,251,137 filed 6/26/01 by McGhan (now Inamed
Corporation)


Exhibit H:

Teuber, SS, Reilly, DA, Howell, L, Oide, C, Gershwin, ME. Severe
Migratory Granulomatous Reactions to Silicone Gel in 3 Patients. J
Rheumatol 1999;26: 699-704

Exhibit I:

Capozzi, A, Dubou, R, Pennisi, VR. Distant Migration of Silicone Gel
from a Ruptured Breast Implant. Plast Reconstr Surg 1978 Aug; 62 (2)
302-3 PMID 353852

Exhibit J:

Adams, WP Jr, Robinson JB jr, Rohrich RJ. Lipid Infiltrations as a
Possible Biologic Cause of Silicone Gel Breast Implant Aging. Plast
Reconstr Surg 1998 Jan; 101 (1): 64-8 PMID 9427917

Exhibit K:

Tang, L, Eaton, JW. Inflammatory Responses to Biomaterials. Am J.
Clin Pathol 1995 Apr; 103-4 PMID 7726145

Exhibit L:

Guidance for Saline, Silicone Gel, and Alternative Breast Implants;
Guidance for Industry and FDA.

Exhibit M:

Dow Corning letter dated 12/27/96 to U. S. Environmental Protection
Agency. Dow Corning letter to FDA dated 1/28/97 in compliance with
the Toxic Substances and Control Act. Agenda for Dow Corning/ FDA
meeting 3/18/97. Dow Corning Mammary Implant Material Formulation
(includes chloroplatinic acid 3-8015 INT PLATNM2).

Exhibit N:

Flassbeck, D, Pfleiderer, B, Klemens, P, Heumann, KG, Eltze, E,
Hirner, AV. Determination of siloxanes, silicon, and platinum in
tissues of women with silicone gel-filled implants. Anal Bioanal Chem
2003;375: 356-362

Exhibit O:

FDA letter dated 3/30/01 in response to Chemically Associated
Neurological Disorders (CANDO) petition Docket Number OOP-1607/CP-1
filed 11/7/00

Exhibit P:

CANDO petition Docket Number OOP-1607/CP-1 filed 11/7/00

Exhibit Q:

Semple, JL, Lugowski, SJ, Baines, CJ, Smith, DC, McHugh, A. Breast
Milk Contamination and Silicone Implants: Preliminary Results Using
Silicon as a Proxy Measurement for Silicone. Plast Reconstr Surg
1998;102: 528-532

Exhibit R:

Lykissa, E. Speciation of Platinum in Whole Blood Samples Compared to
Speciation of Platinum Released From Subject's Implant. Platinum in
Samples of Women with Silicone Gel-filled or Silicone Saline Implants
and Their Children.

Exhibit S:

Naidu, SH, Beredjiklain, P, Adler, L, Bord, FW Jr, Baker, DG. In Vivo
Inflammatory Response to Silicone Elastomer Particulate Debris. J
Hand Surg (Am) 1996 May; 21 (3): 496-500 PMID 8724486

Exhibit T:

Statement at 10/14/03 FDA hearing by Vanessa Rose Ferrelli

Other References

Maharaj, SVM, Platinum Concentration in Silicone Breast Implant
Material and Corresponding Connective Tissue by Inductively Coupled
Plasma-mass Spectrometry.
2003., pers. comm..

Wright, TM, Goodman, SB (eds). Implant Wear: In Total Joint
Replacement. American Academy of Orthopaedic Surgeons, Rosemont, Il.
2000

Ojo-Amaize, EA, Lawless, OJ, Peter, JB. Elevated Concentrations of
Interleukin-1beta and Interleukin-1 Receptor Antagonist in Plasma of
Women with Silicone Breast Implants. Clinical and Diagnostic
Laboratory Immunology 1996; 3: 257-259

Empl, M, Renaud, S, Erne, B, Fuhr, P, Straube, A, Schaeren-Wiemers, N,
Steck, AJ. TNF-alpha Expression in Painful and Nonpainful
Neuropathies. Neurology 2001 May 22; 56 (10): 1371-7 PMID 11376190

Deprez, M, Lubke, U, Verlaet, M, Debrus, S, Delvenne, P, Martin, JJ.
Detection of Cytokines in Human Sural Nerve Biopsies; an
Immunohistochemical and Molecular
Study. Acta Neuropathol (Berl) 2001 Apr; 101 (4): 393-404 PMID
11355311

Lindenlaub, T, Sommer, C. Cytokines in Sural Nerve Biopsies from
Inflammatory and Non-inflammatory Neuropathies. Acta Neuropathol
(Berl) 2003 Jun; 105 (6): 593-602 PMID 12734666

The following organizations support this petition:

Toxic Discovery Network - Missouri
United Silicone Survivors of the World – Houston Chapter
The Breast Implant Information Exchange - Illinois
Silicone Solutions Outreach - Louisiana
United Silicone Survivors of the World – New Mexico Chapter
National Silicone Implant Foundation - Texas
United Silicone Survivors of the World – Florida Chapter
Implant Veterans of Toxic Exposure - Idaho
Coalition of Silicone Survivors - Colorado
Silicone, Saline Information Support System – Nevada
Cen-Tex Silicone Implant Support – Texas
Toxic2KIDS - Missouri
Members of Saline Support Internet Support Groups (Yahoo)
In The Know – California
United Silicone Survivors of the World – Ohio Chapter
Children Afflicted by Toxic Substances – New York
Command Trust - California
Humantics Foundation for Women

United Silicone Survivors of the World – Oregon Chapter


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