Implant Veterans of Toxic Exposure

Dowknew1

What Dow Corning had to say in corporate documents regarding breast implants.

Excerpts From: DOW DOCUMENTS

Document #1
00/00/00
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCEOUS DESREGARD

"Internal Audit and Corrective Action Plan" prepared by Dow Corning of its Toxicology Laboratory. The audit uncovered four studies in which a former Dow Corning employee (Mark Bejarano) created false data and violated Good Laboratory Practices (GLP). The studies which were falsified are a lifetime breast implant gel study in rats, a biodurability study of elastomer in orthopedic devices, a breast implant elastomer study.

The falsification involved the technician, Bejarano. who created multiple slides from a single animal and labeled them as though they had come from different animals. The report states, "It has been acknowledged by Mr. Bejarano that he: did create multiple slides, made a mistake, acted on his own, acted contrary to his Dow Corning training, and did not tell his supervisor or anyone else what he had done." (p.4 or Temporary Dow Corning Bates Number 411) Dow Corning claims that none of the four studies were published or relied on for data on the safety of breast implants, that an outside audit will also be done, and that Dow Corning will examine its operating procedures for the toxicology laboratory to make sure it complies with applicable regulatory requirements.

Appendix A is a list of studies in Dow Corning's PMAA master file and a list of studies in Dow Corning Corporation's blue book. Appendix B is a list of studies containing duplicate slides created by Mark Bejarano. Appendix C is qualifications of the consultant.

CITE: DCC 411000406 - 411000525, Exhibit 25 to Zimmer Deposition; Exhibit 4 to Bejarano Deposition; Exhibit 5 to Bey Deposition; Exhibit 35 to McKennon Deposition.

Document #2
00/00/00
ACKNOWLEDGEMENT OF NEED FOR TESTING
TESTING

Research Project Description titled "Organosilicone Anticholesterol Agents" The intent of this experiment is to isolate organosilicon compounds capable of lowering total serum cholesterol in several species and of ameliorating atheromata in rabbits. Data collected coincidental to other experiments have indicated a number of organosilicon compounds that can lower serum cholesterol, triglycerides, and/or phospholipids in normally fed mice and rats. Dimethylpolysiloxanes can ameliorate atheromata in rabbits.

CITE: DCC 16001089 - 16001091, Exhibit to Bennett Deposition.

Document #3
00/00/00
ACKNOWLEDGEMTN OF NEED FOR TESTING
COHESIVENESS-LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Dow Corning Research Project Description entitled "Metabolism Of Organosilicone Compounds." The intent is to study systematically the absorption, distribution, storage, metabolism and elimination of those organosilicon structures forming the basis of silicon chemistry as exploited by Dow Corning. There have been no systematic explorations of the metabolism of these classes of organosilicon compounds. Such explorations are necessary for their predictive value in selecting and developing efficacious biological applications, and in defining the environmental impact of all present and future products.

CITE: DCC 16001081 - 16001083, Exhibit to Bennett Deposition, and Exhibit to Isquith Deposition.

Document #4
00/00/00
est. 1970
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Draft of the "Proposed Agreement For Cooperative Research Program between Dow Corning and Lepetit Pharmaceutical Company to research the use of silicone compounds in biological systems. "These silicon chemicals

will likely be used systemically rather than locally, and their utility in biological systems. "These silicon chemicals will likely be used systemically rather than locally, and their utility in biological systems may dependent more upon their chemical, rather than their physical properties. (p.1)

The proposal notes that Dow Corning has acquired information that certain silicones are biologically active and has instituted a Biomedical Research Laboratory in July 1965 "to probe the potential utility of such silicon chemicals across the broad disciplines of biology, i.e., plant sciences, microbiology and animal science." (p. 2) Dow Corning Does have the capability to conduct research on silicons in the pharmaceutical areas while Lepetit "has been engaged

in s specific endocrine cooperative research program with DC for a period of two years." (p. 3) The proposal states that the parties would cooperate to develop new silicon chemicals as drugs including silicones with activity as androgen depression, central nervous system depression, antimicrobial activity, etc. (pp. 3-4). Additionally, Dow Corning and Lepetit personnel will exchange research and information and will travel to the other's facilities.

CITE: DCC 2801011379 - 281010391, Exhibit to Bennett Deposition (also used as Exhibit 65 by Dow Corning), Exhibit to Blocksma Deposition (used by Dow Corning), Exhibit to Isquith Deposition, Exhibit to LeBeau Deposition, Exhibit to Petraitis Deposition, Exhibit to Rowe Deposition, Exhibit 17 to Popoff Deposition, Exhibit to Julius Johnson Deposition, and Exhibit to MDL LeVier Deposition. WITNESS: Bennett (Authenticated in Bennett, Vol. II, p. 455-457). DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.

Document #5
00/00/00
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Script of an internal Dow Corning seminar presented by Dr. Isquith, and Tony Bennett and Pat Walters on the subject of microbiology. Isquith states that, "Our (Biomedical Research) primary function is to investigate the microbiology of organosilicon compounds through basic research. A secondary function is the development of utility from the information gathered, either academically or in an applied form. A third function is that of service. We are interested in the preservation, biodegradability, and microbiology of existing Dow Corning products." (p. 2)

Abbott notes that the Microbiology Section has "the capability of conducting research in most areas of microbiology (i.e., Virology, tissue culture, immunology, mycology, bacteriology, etc.)" (p. 3) He notes that one function is to search for organisms capable of silicone degradation. (p.3) There is also a section on Page 3 which is crossed out on Silanols and then a handwritten outline on Silanols (Slide 2) beginning on page 4. Abbott states that silanols have provided "much

basic research information on the relationship of organosilicon compounds to microorganisms and has suggested new areas of research." (p. 6)

CITE: Temporary Dow Corning Bats Number 671 - 685, Exhibit 4 to Isquith Deposition.

Document #6
00/00/00
ACKNOWLEDGEMENT OF NEED FOR TESTING
TESTING

Research Project Description titled "Antiparkinsonism Activity of 2,6-cis- and 2,6-trans-(PHMESIO)2(ME2SIO)2)." The objective is to evaluate (PhMeSiO)2(Me2SiO)2) as an antiparkinsonism agent. It has been shown that these compounds increase whole brain dopamine within 5 days of daily oral administration.

CITE: DCC 16001084 - 16001085, Exhibit to Isquith Deposition, Exhibit to LeVier Deposition.

Document #7
00/00/00
COHESIVENESS - LIQUID COMPONENT OF GEL
MISCELLANEOUS - COMPLICATIONS
TESTING

Report titled "Discussion of Toxicology of Various Dow Corning Products." Topics include gel bleed, silicone transport across the skin, the need for further testing. Dr. Carson recommended that all possible evidence of adverse effects be collected with supporting data of literature on our part to show that Dow Corning has no part in these. The presence of Low Molecular Weight in 350 cs. is the same as in lower cs.

CITE: DCC 281041877 - 281041882.

Document #8
00/00/00
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
TESTING

Handwritten synopsis by Lake titled "Status of Biological Testing of Sila-admantoner Compounds, Dow Corning Report 4234" of research projects and patent activity. It includes notes regarding fibroblasts and immunopotentiation, antigen modification, and joint research on in vitro carcinogen bioassay.

CITE: LAK 133, Exhibit to Radonovich Deposition, Exhibit to Boley
Deposition, and Exhibit to Lake Deposition.

Document #9
00/00/00
TESTING
TISSUE REACTION

Dow Corning document: "I. Silicone Oils As Miticides (or mite-repellents)"; "II. Aphid Control With Silicone Emulsions"; "III. Effect Of Silicone Emulsions On Mealy Bugs"; and "IV. Effects Of Silicone Oils On Cockroaches." The document was authored by "JWR" (unknown who this is). "Mites do not willingly invade silicone treated bean plants if untreated ones are available." (DCC 16001144). Mites are not controlled by silicone-treated cucumber plants, possibly because the silicone oil is absorbed into the plant. A silicone spray was "completely effective in discouraging them. It is possible that a minor component, relatively volatile, may be acting as a contact insecticide." (Id.)

Wild mustard plants sprayed with DC 200 fluid 10 cs. eliminated aphids. "The impression gained is that the insecticidal (or repellent) activity is due to some component of the fluid which has gone (presumably by evaporation or by becoming chemically bound within the plant) or a hydroxy-ended material. It seems worthwhile attempting to identify the active species and trying to modify it chemically to obtain a long-term effect." (DCC 61001145).

Pachysandra plants, infested with mealy bugs, were sprayed with an antitranspirant emulsion with 5% silicone. After 5 days, all mealy bugs on the treated plants were eliminated. "The silicone appears to be slower acting here than upon other insects; possibly a repellent, rather than an insecticidal, effect is involved." (DCC 61001146).

In the 1950s, Texaco and Shell did studies on hydrocarbon oils as insect attractants. In 1968, it was found by Gorzinski (of Dow Corning) that DC 360 fluid appeared to have an insect attractant and insecticidal activity. Cockroaches were attracted to the petri dish with silicone fluid. After coming out of the fluid, they "never got more than a few inches from the dish before dying." These results indicate "some type of activity existed in the DC 360 fluid...." (DCC 61001147).

CITE: DCC 16001144 - 16001147, Exhibit to Bennett Deposition, Exhibit 11 to McKennon Deposition, Exhibit 8 to Harris County Gehring Deposition, Exhibit to Harris County and MDL LeVier Depositions, Exhibit to Ryan Deposition, and Exhibit to Isquith Deposition. WITNESS: Bennett (Authenticated in Bennett, Vol. IV, p. 880;15 - 882:8). DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare.

Document #10
00/00/00
KNOWLEDGE OF SYSTEMIC DISEASE MISCELLANEOUS

LeVier, Dow Corning, memo to C. Lentz and Nelson regarding "Activities Related to 2,6-cis." There are twelve Dow Corning Products currently being sold by the Medical Business that could contain levels of 2,6-cis originating from SBM-18 in excess of the estimated allowable body burden. Medical Products has no active program to identify replacement stock other than conversion of developmental products based on SGM-18 wherever possible. The greatest concern rests with the replacement identified for SGM-18 (elastomer) in that it may be necessary to re-qualify the new stock for medical use including long-term implantation studies.

CITE: DCC 281031092, Exhibit to MDL and Harris County Tyler Deposition, Exhibit 8 to Harris County LeVier Deposition, Exhibit to MDL LeVier Deposition, and Exhibit to Ryan Deposition, NOTE: See document # 11 for attachment.

Document #11
00/00/00
MISCELLANEOUS

Table of 2,6-cis levels in selected products which was attached to LeVier's memo (see document # 10 above). MDX-4-4514 (elastomer), shunts, penile implants, chin implants, and other products all contained 2,6-cis.

CITE: DCC 281031093, Exhibit to Tyler Deposition. NOTE: See document # 10.

Document #12
00/00/00
VIDEOTAPE PRODUCED AT ZIMMER DEPOSITION ON D4.

CITE: No Bates Number, Exhibit to Zimmer Deposition.

Document #13
10/08/92
COHESIVENESS - LIQUID COMPONENT OF GEL
MISCELLANEOUS
TESTING

"Catalog and Review of D4 Studies." This is a list of all studies by Dow Corning on D4. There is a handwritten note at the top that says: "Meeting Oct. 16, 1992, Stark/BeyZimmer."

CITE: DCC 260000855 - 260000878. WITNESS: Exhibit to Zimmer Deposition.

Document #14
00/00/00
MISCELLANEOUS - ORGANIZATIONAL SURVEY
MISCELLANEOUS - LOBBYING

List of "Desired Product Champion Features" includes that the relationship with the product champion should fit the Dow Corning Silicone Group Business Strategy. "PC (product champion) needs to understand and buy-in to the Silicones Group Business Strategy." Listed features include that the PC serve as a substantive resource to Dow Corning, be loyal to the company, have positive peer influence, be politically astute, and demonstrate teamwork with Dow Corning. The document lists the names of product champions in the United States and Europe and includes a manual prepared by Lois Duel dated September 1, 1989 which addresses issues such as the desired product champion features, the role of the product champion, product champion management and specific product champion issues.

CITE: KKA 210877 - 210886

Document #15
00/00/00
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS
MISCELLANEOUS - COMPLICATIONS
TESTING

Confidential report entitled "Chronology of Silicone Injection." The report provides a historical account from Dow Corning's perspective of the use of liquid silicone injections and the establishment of the Center for Aid to Medical Research. It notes that Dow Corning 200 fluid was used for industrial applications. When the Medical Products Division was established in the early 1960's, the 200 fluid was designated Dow Corning 360 Medical Fluid. The report notes that, "The original label on the new product carried the inscription 'formerly Dow Corning 200 Fluid.'" (DCC 267371450) The report also discussed the indictments against Dow Corning officials for distributing the drug, 360 fluid, and the pleas of no contest which were eventually entered.

CITE DCC 267371444 - 267371466. NOTE: The document also has Bates numbers QDC 124506 - 124528 on it as well as Bates numbers MM 369861 - 3698883.

Document #16
00/00/00
ACKNOWLEDGEMENT OF NEED FOR TESTING
SILICA
TESTING
TISSUE REACTION

W.D. Galloway reports on the "Analysis of Lifetime Carcinogenicity Study of Silicone Gels" conducted by Dow Corning under GLP regulations using Sprague-Dawley rats injected with Q7-2159A and MDF-0193 gels.

Galloway states:

"Both of the gel-implanted groups showed a large number of cancers compared to the control group. Particularly striking was the number of sarcomas (principally fibrosarcomas) which occurred in the treated groups."

"The only obvious deficiency is that only one dose level was used. Ordinarily, three doses are used, and five are preferred. Based on the results obtained, I have little doubt that NTP would classify these substances as likely animal carcinogens."

"According to Dow Corning, ... the tumors were peculiar to rats, the so called foreign body tumors."

"Absent epidemiologic data, and without waiting for results of additional lifetime studies, knowledge of the mechanism by which these tumors was induced is critical to estimating human risks. It is possible that the tumors were chemically induced, rather than being induced by a by a physical mechanism, as Dow suggests. If this is the case, then the argument that such tumors do not occur in man is untenable. If the tumors were chemically induced, the active agent is more likely to be one of the several chemicals which make up the gel, rather than a metabolically produced reactive intermediate, since the tumors which did occur did not occur selectively in metabolically active organs such as the liver."

"Recent studies have shown that siloxanes may act as estrogen-like substances and can enhance the growth of tumor cells."

CITE: M 780064 - 780065

Document #17
00/00/00
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
MISCELLANEOUS
SILICA

Dow Corning materials identification list for final devices. It lists all materials used in final devices with a Dow Corning code number. The two manufacturing sites, Michigan and Tennessee, use different identification codes. The list also gives material formulations, indicates the need for a low-bleed outer shell liner, identifies whether "responsive" gel or "firm" gel is used, and notes the percentage of silica used in the formulations.

CITE: KMM 447209 - 4477224

Document #18
00/00/00
Post 10/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
MISCELLANEOUS - COMPLICATIONS
RUPTURE
SHELL STRENGTH - THICKNESS

Dr. O. Gordon Robinson Presents a paper entitled "Rate of Rupture of Silicone Prostheses: Excerpt From A Study Of Over #3000 Personal Cases and Twenty-Five Years Experience" at the Symposium on Reoperative Aesthetic Surgery of the Face and Breast in Naples. Florida. Robinson discusses results obtained after 115 patients were followed after the fall of 1990 after receiving breast implants. Of the 115 patients, 57% had rupture of one or both implants. An additional 20% had moderate to severe bleed on one or both sides. The patients had the implants from six months to 25 years. Dr. Robinson concludes that all gel and bi-lumen implants:

"should be replaced at about the eighth post-operative year because it can be fairly well predicted that at this stage the prostheses in most cases would still be intact and much easier to replace. If a period of time longer than twelve to fourteen years is allowed to elapse, then the prostheses have a good chance of being ruptured and the exchange would be much more difficult.

CITE: PSC Medical Articles CD, J 2698 - Exhibit 2 to Robinson Deposition, Exhibit 25 to McKennon Deposition. WITNESS: Robinson. DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare
Dow Corning Trial Exhibit List

Document #19
00/00/00
Post/10/92
KNOWLLEDGE OF GEL BLEED
MISCELLANEOUS - COMPLICATIONS
RUPTURE
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS

Dr. O. Gordon Robinson's abstract of a paper entitled "Disruption Rate Of Silicone Gel Prostheses - A Report Of 200 Cases." 200 patients from 02/91 - 10/92 had their silicone gel implants removed. The time from implantation ranged from six months to 25 years. Robinson found that 104 or 52% had one or both implants ruptured, 43 or 21.5% had severe bleed, and 147 or 73.5% had "distortion" - rupture plus severe bleed. Based on this data, Robinson projected future rupture rates using the Kaplan-Meier survival curve, and concluded that in 20 years, only 3.4% of the patients will have both prostheses still intact. He states, "Gel filled mammary prostheses wear out and in a certain predictable time frame. Based on this study, patients can be advised with a certain degree of accuracy as to the probable condition of their prostheses."

CITE: No Bates Number, Exhibit 3 to Robinson Deposition. WITNESS: Robinson DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.

Document #20
00/00/00
10/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
RUPTURE
SHELL STRENGTH - THICKNESS

Dr. O. Golden Robinson presents a paper entitled "Breast Implant Removal Or Exchange: which updated his prior study of 200 patients. He has seen an additional 100 patients and presents nine charts of statistics. Chart 2 lists "symptoms" of patients including burning and pain, numbness and tingling in extremities, joint and muscle pain, joint and muscle dysfunction, enlarged liver, flu symptoms, loss of appetite, swelling, arthritis symptoms, fibrocystic disease, deformity, kidney failure, vision problems, chronic fatigue, lupus, rash, insomnia, and hair loss. Of the 300 patients, 154 had a ruptured prosthesis, and 214 had a "disrupted" prostheses, i.e. loss of integrity of the silicone shell or severe silicone bleed where silicone "strings out at least 12 inches from intact capsule." (p.1).

CITE: No Bates Number, Exhibit 4 to Robinson Deposition. WITNESS: Robinson DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.

Document #21
00/00/00
Post 10/92
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
RUPTURE
RUPTURE - CLOSED CAPSULOMTOMY
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS

Dr. O. Gordon Robinson's charts on the age of prostheses a significant number of implants ruptured 6-16 years post-implantation, ( observations at surgery 36.9% of his 73 patients were symptomatic), follow-up (most did not show any change in symptoms during follow-up), symptomatic (patient relates to prostheses-arthritic profile, refer, and "No Closed Capsulotomies"), asymptomatic (patient happy), and questions ("Do mammary prostheses last forever? What contributes to the silicone envelope wearing out? ... How do you tell if an implant is ruptured? ...."

CITE: No Bates Number, Exhibit 9 to Robinson Deposition. WITNESS: Robinson DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.


Document #22
00/00/00
Post 10/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
RUPTURE
SHELL STRENGTH - THICKNESS

Draft of Dr. O. Gordon Robinson's paper entitled, "Breast Implant Removal Or Exchange." This is a draft of document number 22.

CITE: No Bates Number, Exhibit 10 to Robinson Deposition. WITNESS: Robinson. DEPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.

Document #23 through#31
00/00/00 #23
ANY FOLLOW-UP STUDIES BY DR. O. GORDON ROBINSON.

This includes an abstract by Dr. Robinson and Dr. Edwin Bradley entitled "Disruption Rate of Silicone Gel Prostheses - A Report of 200 Cases" published in the January 1995 issue of the American Medical Association Journal.

00/00/00 #24

PHOTOGRAPHS OF PLAINTIFF'S EXPLANT SURGERY

00/00/00 #25

EXPLANTED IMPLANTS OF PLAINTIFF AND PHOTOGRAPHS THEREOF.

00/00/00 #26

MEDICAL RECORDS OF PLAINTIFF.

00/00/00 #27

MEDICAL BILLS OF PLAINTIFF.

00/00/00 #28

PATHOLOGY SLIDES AND TISSUE SAMPLES OF PLAINTIFF.

00/00/00 #29

SPECIMEN BREAST IMPLANTS.

00/00/00 #30

SELECTED COMPLAINT REPORTS, FORMS AND/OR RESPONSES.

00/00/00 #31

ALL PRODUCT DATA SHEETS OF DOW CORNING FOR MAMMARY PROSTHESES.

Document #32
09/14/54
SILICA
KNOWLEDGE OF SYSTEMIC DESEASE

H.C. Spencer, Dow Chemical, note regarding "Dow Corning Hydrophobic Silica." Testing shows a "high order of toxicity from dust inhalation."

CITE: TDC 5488

Document #33
03/28/55
MISCELLANEOUS - COMPLICATIONS
SILICA
TISSUE REACTION

"Report Of Trip To Saranac Lake Laboratories" by V.K. Rowe of Dow Chemical prepared for Dow Corning. Rowe and other Dow Chemical scientists visited Saranac Laboratory to verify work they had done on D.C. Degusa silica for Dow Corning. Rowe, et al. reviewed the work and wrote this report on the conclusions of the tests.

Dow Corning silica consists of crystalline silica. Rowe states that, D.C. Degusa (silica) dust is "capable of causing diffuse cellular infiltration and fibrotic changes in the lungs and other organs of certain types of animals. It also produces bronchitis and sometimes emphysema." However, he concludes that it is not likely to cause silicosis" in the ordinary sense of the word. If fibrotic changes of the lungs develop in man, they will probably be diffuse in character. If exposure is stopped, a measure of recovery is quite possible. Exposure to crystalline free silica reactivates and aggravates tuberculosis & causes progressive lesions." (DCC 299000444).

CITE: DCC 266000443 - 266000453, Exhibit to Lynch Deposition, and Exhibit to California Braley Deposition.

Document #34
01/00/56
TESTING
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Dow Corning Report No. 1377 on "The Physiological Assimilation Of DC 200 Fluid" by M.B. Chenoweth (Dow Chemical), R. Holmes and F. Stark. A copy was distributed to Collings, Bass, Kauppi, Hunter, Hutchison,

Hyde, Blackburn, Bennett, McHard, CRI, and others including Beamer of Dow Chemical. "An increasing use of siloxanes for medicinal applications has resulted in the need for information on their biological activity. Previous experiments of The Dow Chemical Company Biochemical Department has shown that many of these compounds were toxicologically inert. It was the purpose of this experiment to determine to what extent the polydimethylsiloxanes were assimilated, and if so were they were metabolized." (I 169). C14 labeled PDMS in antifoam emulsion was administered to 2 albino rats and 2 lactating dogs. "The preoperative care, administering of the labeled fluid, sacrificing and dissecting of the animals was carried on by Dr. M.B. Chenoweth of The Dow Chemical Biochemistry Department. Samples of tissue were analyzed with the cooperation of Dow's Radiochemistry Laboratory." (I 171). With intramuscular injection, the C14 siloxane was found in the intestines, right adrenal, skin and hair, heart, skull bone, brain, kidney, urine, liver, muscle, lung, renal fat, blood and spleen. (I 172). Rats fed with the material had siloxane in the ileum, stomach and content, bladder and urine and kidney. (I 174). "The actual amount present may be greater by a factor of 3 corresponding to total polydimethylsiloxane from Dow Corning 200 Fluid and from gum. It is unlikely that the polydimethylsiloxane in the gum would be more readily assimilated than the lower molecular weight 200 Fluid." (I 174). A lactating dog fed with the material has siloxane in the skin and hair, brain, bile,, liver, kidney, heart, milk, urine, skeletal muscle, lung, adrenal, and blood. (I 175). A second lactating dog also had siloxane in the bile, skin and hair, adrenal, urine, spleen, lung, heart, liver, thyroid, pancreas, blood from lung, skeletal muscle, and milk. (I 175).

"The studies conducted along these lines (C14 labeled fluid) to date have shown that these compounds are absorbed from the gastro-intestinal tracts to a slight extent, the amount absorbed being of the order of .0001%. Toxicological studies have shown these compounds to be inert." (I 175). There is a cite to the lab notebooks for the studies. On 259803.

CITE: KMM 259794 - 259803, Exhibit to Harris County LeVier Deposition, Exhibit to Tyler Deposition, Exhibit 20 to Harris County Zahalsky Deposition. DUPLICATE: I 167 - 176.

Document #35
02/09/56
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS
MISCELLANEOUS - COMPLICATIONS
TESTING

McGregor, Dow Corning, memo to Rowe, Dow Chemical Biochemical Research, enclosing 9 samples of silicone fluids for determination of the effect of intravenous injection. McGregor wants to know if any of the silicone fluids can be tolerated when injected intravenously. The silicone samples include 200 fluid, 555 fluid, 710 fluid, antifoam AF emulsion (which contains 30% 200 fluid), and XEC-5027 (which contains 10% 200 fluid).

CITE: OOT 43674 - 43700, Exhibit to K. Olson Deposition, Exhibit to Rowe Deposition, Exhibit 24 to Harris County Rowe Deposition. and Exhibit to McHard Deposition.

Document #36
08/00/57
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Stark titled " The Physiological Activity Of Dow Corning 200 Fluid." By a mechanism unknown at this time, a small amount of Dow Corning 200 Fluid is absorbed through the skin by the adrenal and kidneys of a rabbit.

CITE: KMM 259804 - 295808.

Document #37
10/05/57
COHESIVENESS - LIQUID COMPONENT OF GEL
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Dow Corning's version of a "Report Prepared for Dow Corning Corporation, Midland, Michigan on Five Silicone Materials." The original report (see document #38 below) was prepared by Dr. W. Deichmann of the University of Miami on October 5, 1957 but was a report on six silicone materials. This version of Dr. Deichmanns report was altered to delete one compound and to delete all adverse effects identified in Dr. Deichmann's original report.

In this version, five Dow Corning silicones were fed to albino male and female rats for a period of 90 days. The silicones were Dow Corning 200 Fluid (50, 350, 1000, 10000 and 60000 cs.). Based on the observations of body weight, food intake, hematology, organ weight at necropsy, and their gross and microscopic appearance, it was concluded that none of the Dow Corning 200 Fluids of the viscosity range fed caused any harmful or deleterious effects.

CITE: KKM 7896 - 7930. NOTE: Includes a summary of animal safety studies relating to dimethylpolysiloxane fluid. See document #38 for the original, unaltered version of Dr. Deichmann's report produced by Dow Chemical. This altered version of the report was produced by Dow Corning.

Document #38
10/05/57
COHESIVENESS - LIQUID COMPONENT OF GEL
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Dr. W. Deichmann's original "Report Prepared for the Dow Corning Corporation, Midland Michigan on Six Silicone Materials" Six Dow Corning silicones were fed to albino male and female rats for a period of 90 days. The silicones were Dow Corning 200 Fluid (50, 250, 1,000, 10,000, and 60,000 cs.) and Dow Corning Z-4141 Solvent Free (the latter compound is the compound deleted by Dow Corning is document #37 above).

ORIGINAL REPORT
DOW CORNING ALTERED REPORT

2 rats died during experiment
only 1 rat died

was a marked decrease in the number of leukocytes. This difference is considered statis tically significant.
there was an apparent decrease in the number of leukocytes. This is not statistically signi ficant.

It is apparent there is a depression in the output of granulocytes by the bone marrow.
The dietary feeding of DC 200 fluids had no significant effect upon the leukocyte counts of the treated animals.

The livers of the rat fed Z-4141 were significantly greater than the controls. This is consistent with the observation of liver damage in these animals
None of the organ weights differed from the controls.

The feeding of the six compounds depressed the granulocytic elements of the peripheral tail blood of female rats. The livers of the rats fed Z-4141 were significantly heavier than the livers of the controls and also demonstrated fatty infiltration or degeneration.
The feeding of the five compounds had no harmful or deleterious effects.


CITE: TDC 6079 - 6100

Document #39
10/09/57
COHESIVENESS - LIQUID COMPONENT OF GEL
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Dr. Deichmann, University of Miami, writes to McGregor, Dow Corning, enclosing the results of the review of the six Dow Corning silicone compounds. He informs McGregor that all six compounds depressed the granulocytic elements of the peripheral (tail) blood of the female rats, and that the livers of rats fed Z-4141 were significantly heavier than the controls and demonstrated fatty infiltration or degeneration.

CITE: M 420103.

Document #40
12/09/57
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Letter from K.J. Olson and checked by V.K. Rowe, Dow Chemical Biochemical Research, to R.R. McGregor of Dow Corning with copies to H.H. Gay (Dow Chemical) and E.M. Adams (Dow Chemical ??) on "Results Of Range Finding Microbiological And Toxicological Tests on B-756-92 (a linear dimethylpolysiloxane of 6 units end-blocked with 2,4,5-trichlorophenxy radicals - being evaluated as potential fungicide for athlete's foot)." The tests showed appreciable antifungal activity. "If large amounts of the material are allowed to remain in contact with large areas of skin, absorption may result in systemic injury and may even produce death." Slight hyperemia followed the 3rd and 4th application and the rabbit died "possibly due from systemic injury due to absorption through the skin." The other 2 rabbits also died.

Attached is a data sheet prepared by Olson and McCollister, a toxicology work sheet, "Request For Applications Testing," and eye contact, skin contact - irritation, and skin contact absorption test records. NOTE: The document is stamped, "This Report Is The Property Of The Dow Chemical Company."

CITE: TDC 6158 - 6175, Exhibit to K. Olson Deposition, and Exhibit to McHard Deposition.

Document #41
04/09/58
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

"Pharmacological Test Data For Various Organofunctional Silicon Compounds, Report No. 1641," by Speier of Dow Corning. Pharmacological screening test data for 61 organofunctional silicon compounds are examined for use in drugs. In early 1952, a program was agreed upon with Eli Lilly for the pharmacological examination of assorted organofunctional silicon compounds. "The screening of these compounds has shown that a great many organofunctional silicon compounds and polymers have totally unexpected activities. Certain ones proved to be acutely toxic, even though closely similar structures were not especially toxic." (DCC 281002214).

All the results are contained in Mellon Institute notebook 318 - all 61 tests in this study contain a reference to notebook 318. There is also a reference to Earl Warrick's work at the Mellon Institute at 281002226.

CITE DCC 281002213 - 281002230, Exhibit to Tyler, MDK and Harris County Depositions, Exhibit to Bennett Deposition, Exhibit to McHard Deposition, and Exhibit to Ryan Deposition.WITNESS: Bennett (ancient document exception to hearsay). DISPOSITION: Not introduced in Toole (II) v. Baxter Healthcare.

Document #42
07/31/58
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Olson, Dow Chemical Biochemical Research, letter to McGregor, Dow Corning, with copies to Gay, Dow Chemical, and McHard regarding the results of skin irritation, skin absorption and acute oral feeding tests on Dow Corning 555 Fluid and Ethylan (a modified lanolin), file no. T2.42-54-1.

In McGregor's 06/05/58 letter to Rowe he indicated that Helen Curtis Industries had observed untoward systemic effects in rabbits and rats due to absorption of the material through the skin. Autopsy revealed small yellowish bubbles and petochone (illegible) on the liver and lungs. Olson applied the material to the skin of rabbits and fed it toanother group for 5 days/ The results for the skin sensitization tests are illegible. There was a questionable to mild kidney disturbance in animals fed 555 fluid.

The conclusions on 6532 state that DC 555 fluid has a low acute oral toxicity, is essentially non-irritating to the skin upon prolonged repeated contact, and that there is no indication that the material is absorbed through the skin in sufficient amounts to produce systemic damage. Attached is a toxicology work sheet, "Requests For Screening Or Application Testing," and skin contact absorption and acute oral toxicity test results.

CITE: TDC 6526 - 6555, Exhibit to McHard Deposition, and Exhibit to K. Olson Deposition.

Document #43
07/05/62
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Olson and Sadek, Dow Chemical Biochemical Research, letter to McHard, Dow Corning, on toxicity by subcutaneous injection of Dow Corning 200 Fluids and Dow Corning 555 And 550 Fluids. Dow Corning 200 fluid 10 cs. resulted in a moderate inflammatory response in the subcutis as indicated by the presence of polymorphonuclear cells and a very large mononuclear cells. "This type of inflammatory reactions is interpreted as due to infection." With DC 555 and 550 Fluid, all injection sites showed evidence of inflammatory reaction indicated by the presence by mononuclear cells and polymorphonnuclear cells.

CITE: TDC 7493 - 7515, Exhibit 9 to Hancock Deposition, Exhibit to McHard Deposition, and Exhibit to K. Olson Deposition

Document #44
07/12/62
SHELL STRENGTH - THICKNESS
S. Braley, Dow Corning, reports on a telephone call with Dr. Gerow regarding his findings from the use of the saline silastic prosthesis. A leak was discovered during implantation and Dr. Gerow "sealed it with cement on the operating table...." Also, he wanted Dow Corning to "make the Gel gooier." Dr. Gerow reports that the saline he has been using in some of the silastic sacs has been in animals for nine months and that the body sets up a chemical balance. He has analyzed the fluid inside the sacs after this nine months and found protein, SO4 ions and also indications that the body had set up a balance of magnesium and other ions. Finally, Dr. Gerow stated that the "direct injection technique has worked out beautifully."

CITE: M 320001 - 320002

Document #45
09/14/62
TESTING

Dow Chemical Texas Division, Agricultural Research, study by F.C. Turner, K.G. Seymour, and J.B. Jackson on "Tropical Application Of Various Solvents And Solutions To Evaluate Dermal Irritation." Report No. 210. The report was circulated many persons including K.W. McCory of Dow International; persons at Bioproducts: Adm., J.E. Johnson; An.Sci. R and D, T.A. Hymas; Plt.Sci. R and D, K.C. Barrons; Midland BRC Files, L.J. Lippie: Registration Section. G.E. Lynn; Synthesis Group, W. Reifschneider; and Formulation Res., J.W. VanValkenburg; to V.K. Rowe of Biochemical Research; and to the following persons at Pitman-Moore: C.W. Hinman, G.R. Burch, and D.C. Brinkman.

Dow Corning 200 fluid - silicone oil with 49% espesol 5 content was administered in 10 cc dosages to shaved strips on the hide to test for suitable solvents for Ruelene. Dow Chemical hoped to find a solvent that didn't damage the hides of cattle when Ruelene was administered. The DC 200 fluid was rated ad bad, which indicated that the hide had extreme cracking or sloughing at 10 and 16 days after application. (TDC 7542).

CITE: TDC 7537 - 7543

Document #46
10/04/62
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF LIQUID SILICONE DANGERS
SHELL STRENGTH - THICKNESS
TISSUE REACTION

S.Braley, Dow Corning, memo regarding telephone call to Dr. Thomas D. Cronin. Braley told Cronin that the uncatalyzed breast material could not be sent out because there were too many problems with it. The problems with measuring and the variability of both the base material and the mixing techniques necessitates different amounts of cross-link resulting, along with the variability in mixing techniques, can cause difficulties.

Dr. Frank Gerow was also on the telephone and talked about the results he was getting regarding tissue reaction to the direct injection of the material.

Cronin said that he is not concerned about leakage if he were to use the thin material because a film forms around the implant retaining the material in place. Cronin said that he is getting chlorine, potassium and proteins both in and out through the wall of the bag. This is on apparently good bags.

It was decided that it would be wise to continue the work for long range testing for the acceptability of the material.

CITE: OOM 320665 - 320666

Document #47
10/31/63
KNOWLEDGE OF LIQUID SILICON DANGERS
GEL MIGRATION


Dr. Walter Berman writes to Silas Braley, Dow corning, reporting on his injection of silicone fluid in mice. Two days after injection, silicone was found in most organs including the brain, liver, spleen, intestinal wall, adrenal and kidney. He also found "evidence of at least radio activity and most probably silicone in the brain and all of the various other organs...."

CITE: M 420051 - 420052

Document #48
11/27/63
TESTING
TISSUE REACTION

Dow Chemical's Bioproducts Department report by Whitney, Pollock and Pauley on "Fluorosilanes As Fumigants." Six flourosilanes:K-56,425 = n-propyltrifluorosilane; K-56,426 = ethylmethyldifluorosilane; K-57,317= trimethylfluorosilane; K-59,489 = mehtyltrifluorosilane; K-59,697 =chlorometthyldifluoromethylsilane; K-58,739 = silicon tetrafluoride; andK-681 = methyl bromide were evaluated as fumigants for control of insects and microorganisms. All were very active against post-embryonic stages of tests insects. Tri and difluoro silanes were active against bacteria and molds. Most of the compounds killed all flour beetle eggs at one lb/1000 cu. ft. with a 16-hour exposure.... A patent disclosure has been submitted and further research is recommended for these and related compounds.

Results of toxicological work with mammals is reported in reports 55.11-56425-1, 55.11-56426-1, 55.11-56427-1, 55.11-57317-1, and 55.11-2-1. the usefulness of these compounds has been reported in Patent Disclosure no. 16193. NOTE: None of these reports or patent disclosures were produced to the PSC.

"Further exploration of the biological and physical properties of these and related compounds is recommended."

CITE: TDC 8901- 8904

Document #49
00/00/64
MISCELLANEOUS - COMPLICATIONS
SILICA STERILIZATION/CONTAMINATION
TISSUE REACTION

Braley, Dow Corning, states in the Trans American Society of Artificial Internal Organs, "The Medical Silicones," that electrical charges exist on the surface of the silicone elastomer. Silicone elastomers are described as non-adherence products, nothing will stick to them "However, because of the dialectic (sic) properties of silicone rubber, it will develop a surface charge and can hold dust, lint, (etc.).... This is not true adhesion." Additionally, the reason

that the attempt to create a silicone vascular prostheses, to be inserted in a blood vessel, failed is because of the electrical charges on the surface which caused the blood to clot at the ingress end of the silicone prostheses tube.

Braley also describes the chemical composition, the characteristics and the various applications of silicone.

Document #50
01/13/64
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

McHard memo to Hunter with copies to Braley, Dingman, Hobbs, and Stebleton regarding "Notes on visit to Battelle Memorial Institute on December 19, 1963." McHard and Hobbs met with representatives of Battelle and discussed the "Toxicology of silicones - past and future. ... 1. Variation in toxicity with animal species. 2. Effect of polymer size on toxicity. 3. Extent of body metabolism. 4. Fate in kidney and liver. 5. Fate of catalysts. 6. Extent of carcinogenicity." Also discussed was silastics for breast implants. Battelle's study showed that the physical properties of silicone rubber when implanted were significantly affected/decreased. Also, "There was considerable discussion on how the various polymer sizes may be transported across the G.I. tract and how they may find their way into the kidney, liver, and subsequently, the urine."

CITE: KMM 299059 - 299063

Document #51
05/16-17/64
COHESIVENESS-LIQUID COMPONENT OF GEL
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Silicone Injection committee Meeting on 05/16-17/64 attended by D.J. Badamo, S. Braley, C.E. Haberstoch, R.R. McGregor, E.G. Mullison, S.L. Bass, H.D. Dingman, E. Hodnett, M.J. Hunter, J.A. McHard, A.W. Rhodes and L.F. Stebleton of Dow Corning; by Drs. Ashley, Blocksma, Dingman, Edgerton, Goulian, Lederer, Murray and Rees, who are medical consultants; and by Steve Carson and Bernard Oster of Food & Drug Research Laboratories. Materials considered for the injectable trials: dimethyl siloxane 360 Medical Fluid "(formerly 299 fluid)"; phenylmethyl siloxanes including 555- "cyclic, very low molecular weight, 704 - linear, very low molecular weight, 550 - dimethyl and phenylmethyl copolymer; large amount of phenyl...." and others.

CITE: DCC 267371390 - 267371417, Exhibit to McHard Deposition, and Exhibit to K. Olson Deposition. DUPLICATE: m 30531 - 30558; KMM 183981 - 184009.

Document #52
05/28/64
FRAUD/MISREPRESENTATION
GEL MIGRATION
MISCELLANEOUS - COMPLICATIONS
TISSUE REACTION

Braley memo to Ashley, Blocksma, R. Dingman, Edgerton, Goulian, Lederer, Murray, Rees, Badamo, Bass, H. Dingman, Haberstroh, Hodnett, Honter, McHard, Mullison, Rhodes, and Stebleton regarding the attached article in the May 25, 1964 issue of "The Insider"s Newsletter." Unknown factors with silicone injections include absorption, migration and hardening.. Braley writes, "We have no knowledge where the reporter obtained this information. If anyone knows anything about this, we'd appreciate hearing from him. We are trying to keep such articles as this out of the public eye as much as possible."

CITE: M 350063 - 350064

Document #53
09/22/64
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Thomas Rees letter to Braley, Dow Corning, regarding the finding of altered fat cells in animals subcutaneously injected with silicone. Rees states that the spleens of the mice that have been injected with massive amounts of the material show definite collection of silicone within macrophages.

CITE: KMM 167416
Document #54
09/24/64
TISSUE REACTION
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS

Letter from Dr. Thomas Cronin to William Rhodes, General Manager of Dow Corning. Dr. Cronin reports that Dr. Brauer had to remove seven implants when, at intervals of 2-4 months, a blister would start in the scar and gradually break down. "(S)ome clear, straw colored fluid would be released".

CITE: KMM 150269 - 150270. NOTE: Ivory flakes were being used to prepare the implants prior to surgery.

Document #55
11/12/64
EMBOLISM
KNOWLEDGE OF LIQUID SILICONE DANGERS

Harry Dingman, Dow Corning's Legal Counsel, writes to Ban Smart of the FDA and informs him of a reported fatality following injection of a silicone. Dr. Crenshaw, California, injected a woman with silicone (source and type unknown) mixed with a vegetable oil. she "then went into a coma in a matter of a few hours, and died within a few days. Dr. Aronow had not received a formal coroner's report, but the informal comment was to the effect that death was due to fat emboli in the lung and possibly in the liver. A suspicion of possible encephalitis was being checked by having a culture run on the brain." (emphasis added).

CITE: KKM 1275 - 1276. DUPLICATE: KMM 48637 - 48638.

Document #56
12/00/64
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - COMPLICATIONS
TISSUE REACTION

"Tissue Reactions to Injected Silicone Liquids, A Report of Three Cases," Archives of Dermatology, Vol. 90, 538-593 by Winer, Sternberg, Lehman and Ashley. Drs. Oppenheimer and Russell observed fibrosarcomas developing in 1.7% to 40% of the test animals. Drs. Hur and Neuman observed malignant epithelial tumors that were believed to be of sweat gland origin. The conclusion drawn from the test data is that "there seems to be sufficient evidence at this time that complications of this nature are to be expected."

CITE: I 253 - 259, Exhibit 7 to McGhan Deposition, and Exhibit 16 to California Braley Deposition. DUPLICATE: PSC Medical Articles CD, J 3598 - 360

Document #57
12/08/64
KNOWLEDGE OF LIQUID SILICONE DANGERS
TISSUE REACTION

Dr. Franklin Ashley writes to Silas Braley, Dow Corning, regarding a "girl in Las Vegas who received the injections and had the eye trouble." The 28 year old woman received 30 injections into the breast.

Ten to fifteen minutes following her final injection she noted onset of nausea followed by dizziness and almost complete loss of vision. At the same time she developed severe left anterior chest pains without dyspnea or tachypnea.

She was seen by an Internist who treated her with ACTH thinking that this possibly represented an anaphylactoid reaction. Visual disturbance cleared somewhat with ACTH. During this immediate post treatment period she experienced some loss of memory, as well as poor coordination which cleared gradually over a period of time. Also noted during this time was hematuria which lasted for one day only; no recurrence has been noted.

One week following the onset of symptoms she was evaluated by Dr. Albouth, at which time he noted a questionable positive Rhomberg and ophthalmologic findings consisting of some loss of visual acuity and hemorrhages within and anterior to the retina.

Follow-up to date has been over a six month period with the latest notation that her gait has returned to normal. Her dizziness has disappeared, but she still experiences some visual difficulties, specifically loss of visual acuity.

CITE KKH 63126 - 63127

Document #58
01/29/65
KNOWLEDGE OF LIQUID SILICONE DANGERS

Franklin Ashley, UCLA Center for the Health Sciences, to Braley, Dow Corning, reporting the death of a patient after various injections of silicone around the face.

CITE: M 340057

Document #59
04/01/65
CONCEALING FROM FDA
KNOWLEDGE OF LIQUID SILICONE DANGERS

Dr. Franklin Ashley responds to Silas Braley's, Dow Corning, letter concerning a girl in Argentina who was injected with large amounts of silicone fluid. "I believe this would fit in also with the observations of Goulian and others where a large quantity was injected any one time, and was taken up by the lymphatics. We have not observed this in any of our cases, however, probably due to the fact that we inject only a small quantity each time.... I do not think this should be reported to the FDA as it is an isolated case and from another country, and we do not know exactly what they injected really." (emphasis added).

CITE: M 340044

Document #6005/27/65
EMBOLISM
KNOWLEDGE OF LIQUID SILICONE DANGERS

Frank Ashley, M.D., reports to Silas Braley of Dow Corning regarding a consultation with a patient in Las Vegas. Ashley states, "My diagnosis, of course, was multiple silicone emboli from the liquid silicone and possible additives, in the lungs, brain, liver, kidney and retina." (emphasis added).

CITE: M 340037

Document #61
06/24/65
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Dr. T. Rees writes a letter to Dr. Silas Braley and Fred Dennett, Dow Corning Center for Aid to Medical Research. Dr. Rees states "The inevitable has happened. We found a case of carcinoma of the breast in a 37 year old woman who has had both breast heavily injected with pure silicone material." He states'

"The carcinoma itself was a very small, isolated, intraductal type of carcinoma in the upper portion of the tail of the breast and there were some involved lymph nodes in the axilla. There are multiple 'silicone cysts' throughout the tissue and some of the silicone was injected in the immediate vicinity of the carcinoma. Also of considerable interest is that there is evidence of silicone deposits in the lymph nodes of the axilla and thus it appears that the silicone is drained to a certain extent by the lymphatic system..... We are thinking of writing this up as a case report, but would like the view of the entire committee before we commence doing so. We are hesitant to report it because undoubtedly it will create quite a stir but feel that the case must be reported for the sake of thoroughness and completeness. We are open to counsel as to just what manner this should be done. (emphasis added).

CITE: KMM 105815 - 105816, Exhibit to D. McGhan Deposition. DUPLICATE: KMM 3802 - 3803.

Document #62
10/05/65
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - COMPLICATIONS
SILICA
TESTING

Hobbs memo to Snedeker with copies to McHard regarding "Recommendations for the toxicological evaluation of J. Treated Dow Corning Silica Type A." "At the present time very little is known on the toxicity of the various treated silicas at Dow Corning.... The exact toxic manifestations are unknown. They will cause death in laboratory animals by various routes of administration, including inhalation, for a period of four hours or less. Although these are high concentrations for a short period of time. we must assume until proven otherwise that low concentrations over long periods of time are detrimental to health. It is therefore our recommendation that acute range-finding studies be performed on J Treated Silica." Testing programs (such as annual chest x-rays of workers) have been run with the cooperation of the Dow Medical and Biochemistry Departments on problems which have arisen with various chemicals. The programs at Dow and Dow Corning were dropped but, "Recently problems have arisen with chemicals and compounds which indicate that such a preventative medical testing program is not only desirable but also advisable.... While toxicity studies are being carried out on some of these materials at the Dow Biochemistry Department, they are made with animals, usually on short term acute exposures. This type of information does not indicate what might happen over long periods of time subjected to less than acute exposures." The document also talks about a Medical-Biological-Safety Committee."

CITE: KKA 230245 - 230249, Exhibit to McHard Deposition and Exhibit to K. Olson Deposition.

Document #63
10/27/65
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
GEL MIGRATION
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS
TESTING
TISSUE REACTION

Burdick, Dow Corning, memo to Don McGhan, Weiler, VerVoort, and Pellikka regarding "Mammary Implants." He states:

"There are still a number of questions concerning our breast units that have not been answered. We know that a quantity of low molecular weigh material is exuding from the bag, but that is all.

He suggests a test to extract the material and analyze it. Burdick states:

"This test should tell us how the gel is affecting the rubber bag. Adhesion and tear strength should also be related to swell. The extractables may be of low enough molecular weigh to migrate throughout the body. If so, what quantity are we talking about?

CITE: OOM 321439 - 321449, Exhibit to Bennett Deposition and Exhibit to D. McGhan Deposition

Document #64
11/15/65
EMBOLISM
KNOWLEDGE OF LIQUID SILICONE DANGERS

Dr. Ashley authors a paper, "Silicone Fluid And Soft Tissue Augmentation, as a result of the Boca Raton symposium. "Of significance is the fact that the clinical use of silicon liquids in man preceded any responsible and controlled experiments in animals." As a result of the concern, ASPRS set up a committee consisting of Dr. Franklin Ashley, Dr. Ralph Blocksma, Dr. Reed Dingman, Dr. Milton Edgerton, Dr. Dicran Goulian, Jr., Dr. Francis Lederer, Dr. Joseph Murray, Dr. Norman Orentreich, and Dr. Thomas Rees.

Dr. Ashley provides a historical overview of the chemical properties and development of silicone. He notes that with intravenous injection of silicone fluid in animals, large doses are usually fatal in rabbits and can produce emboli and death in dogs. He found no tissue reaction in animals when liquid silicone was injected subcutaneously.

Dr. Ashley also notes that silicone oil "will have a tendency to disappear" within the body and that:

"(S)ignificant questions ... remain unsolved. First, what is the body distribution within its tissues of any absorbed material? Second, what is the ultimate fate of the absorbed material? ... Third, if significant amounts are absorbed, does the body excrete the material, and if so, how, and how much? Fourth, if some is retained, in which organ or organs is a harmful effect produced - if any? Indeed, there is some evidence that silicone oils may be transported to far removed tissues and organs. In another study, one week after the intramuscular injection of a rat with dimethyl polysiloxane, 90 per cent of the C(14) labeled liquid oil was detected within the tissues of the intestinal tract. The fate and presence of silicone oil in human biology is unknown." (emphasis added). He further notes that, "In large subcutaneous injections of silicone fluid, examination of the contents of the abdominal cavity showed that the mesenteric and omental fat was abnormally firm, with loss of normal color and adherence to adjacent viscera. This suggests that there may have been transport of silicone oil through the abdominal cavity."

Animal studies of injection of RTVS 5392 silicone fluid showed tumor development in rats at eight, fifteen, and nineteen months after injection. MDX 44010 silicone fluid was also injected in mice, rats and monkeys. Nearly all animals developed hair loss over the implanted site, and several rats developed superficial cutaneous ulcers directly over the silicone mass. Both of these symptoms resolved themselves within six weeks. He also noted a significant "exothermic reaction," "pronounced local reactions," and tumor development in 3 of 6 rats at 14 and 16 months post-injection. He concludes:

"Although it is only speculation, the initial exothermic injection reaction and tissue injury may have provided a carcinogenic influence.... (T)he incidence of 3:6 (3:22) should not be attributed to random chance occurrence.... Tumor formation about buried synthetics has had important consideration by some, but discounted by others.... (A) tumor incidence of 3:6 or 3:22 indicates a need for further animal experimentation." (emphasis added). He notes that human clinical experience in 35 patients noted breast abscess and apparent tumor formation. He reports on three cases of carcinoma of the breast in women following injection of silicone fluid. One woman developed a palpable axillary lymph node eight months following injection and required a radical mastectomy. Surrounding the cancerous lesion were "multiple small silicone cysts. The silicone was also found in the axillary lymph modes removed with the radical specimen."

"At least two deaths are known to have followed the subcutaneous injection of 100.0ml. or more of Dow Corning 360 Medical liquid given in one single administration.... At least one patient is known to have developed blindness during the subcutaneous injection of Dow Corning 360 Medical liquid.... There is no reason to believe that the human will tolerate intra-arterial and/or intravenous injections any better than the experimental animals. (emphasis added).

CITE: M 360096 - 360141

Document #65
01/14/66
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

McHard memo to Bass with copies to Bennett, Dingman, Hunter, W.T. Rossiter and Rowe regarding "Toxicological testing of Dow Corning Pan Shield." McHard is reporting on the results of a meeting today with Rowe and Bennett regarding DC Pan Shield. An initial formulation of this product indicated no apparent toxicological problems. However, the catalyst wasn't potent enough to cure on the pan; therefore a new catalyst was used and the product reformulated. Based on the results of the testing with the first catalyst, no toxicological problems were anticipated and so marketing decisions were made about the product. As they got into the 90-day testing program, the toxicological information was insufficient to assure the degree of product safety necessary. Therefore, Rowe, Bennett and McHard met today (1/14/66) to review this product. "(I)t is our recommendation that marketing studies, even short-termed pilot tests, be postponed until product safety data can be accumulated."

There are indications that adequate non-toxic oral levels may not be achieved. "It should also be borne in mind that if Dow Corning were obliged to defend the safety of this product today in a court of law, we would be at a serious disadvantage since we could be forced to disclose all data which has any bearing on the components of the product. You can well appreciate what our position would be in this event?"

CITE: DCC 281041086 - 281041087

Document #66
06/06/66
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Minutes of meeting with the FDA in Washington DC regarding Dow Corning 555 Fluid. Present were Steve Carson and Bernard Oser (FDRL), Otis Fancher (IBT), Bass, Bennett, Dingman and McHard (all of DC) and Drs. Lehman, Marzulli and Nelson with the FDA. McHard reported on the chemical composition of DC 555 and a summary of Dow Corning's 555 fluid Safety Evaluation Program. DC 555 has been used in cosmetic preparation for 12 years. It was decided to have more detailed subacute tests performed on rabbits at IBT. The testicular size of the test rabbits was reduced and spermatogenesis was depressed on microscopic examination. The effect was traced to the DC 555 fluid in the hand cream. FDRL then evaluated the fluid and found no such activity in rats or guinea pigs, noted a marginal effect in dogs, and observed activity in the rabbit but not as severe as that noted at IBT.

"A consultation was held with Drs. Oster*, Carson*, Calandra (Industrial Bio-Test Labs.), and Rowe, toxicologist of the Dow Chemical Company. These consultants felt that the data were indicative of a species specific response and therefore it was suggested that a male monkey series be started in which the material would be applied dermally repeatedly." The studies were done at IBT. A dose applied dermally repeatedly." The studies were done at IBT. A dose of 5 mg.kg. produced a statistically significant effect. McHard mentioned that "the effect requires 20 days of daily application in the rabbit, but the effect is not grossly present until the 16th-17th day.

Oral studies in monkeys was begun in 1965. It was noted that in the orally dosed males, it was difficult to obtain ejaculate and a subsequent biopsy at 5 months of oral dosing in the males showed a marked depression of spermatogenesis at the 2000 mg.kg. level, and 2 of 3 monkeys showed spermatogenic depression at the 50 mg.kg. level.

McHard commented on the isolation of chemical species to determine the active agent. Dow Corning has not yet identified the specific structure which causes the observed systemic effect. McHard also commented on the quality-control of the product. McHard also noted that no ill effect had been observed or reported from people at Dow Corning exposed in the production area. Dingman hoped that the findings on DC 555 fluid would not cast any reflections on DC medical grade 360 fluid or industrial grade 200 fluids.

CITE: KMM 418744 - 418775, Exhibit to Bennett Deposition, Exhibit to Rowe Deposition, and Exhibit to McHard Deposition.

Document #67
07/00/66
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

T. Rees, et al., submits to Dow Corning a report titled "Visceral Response to Subcutaneous and Intraperitoneal Injections of Polymethylsiloxane in Mice" which evaluates histologically the systemic distribution of silicone fluid. Results indicate silicone deposition in the spleen, liver, adrenals, pancreas, ovaries, abdominal lymph nodes and kidneys of the test animals, suggesting distribution by the reticuloendothelial mechanism.

CITE: KKM 31076 - 31087

Document #68
08/02/66
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Braley memo to Ashley, Blocksma, Dingman, Edgerton, Goulian, Lederer, Murray, Orentreich, Steve Carson, Bennett, Bennett, Hunter and McHard regarding the attached letter and paper from Thomas Rees. Rees' letter is dated 7/26/66 and notes that this is a privileged communication. "I hope this work doesn't open a can of worms but I can't see any alternative to publishing it." The draft paper notes that subcutaneous administration of massive amounts of silicone produces considerable alteration of the tissue structure of the subcutis. The fat cells in the immediate vicinity of the encapsulated silicone show varying degrees of atrophy and the intracellular fat contains small regular vacuoles. Intraperitoneal injections or subcutaneous doses in excess of a total dose of 7 ml in mice resulted in widespread microscopic lesions by 3 months. The silicone also produced a generalized alteration of the abdominal and epicardial adipose tissue. The fat cells showed a finely granular, eosinophilic cytoplasm. "In many abdominal organs which included adrenals, lymph nodes, liver, kidney, spleen, pancreas, and ovary, focal infiltrates of macrophages with abundant clear cytoplasm were encountered. The nature of the cytoplasive material within the macrophages has not been ascertained, but it is presumed to be silicone as those lesions did not occur in control animals. The early adrenal lesions were found at the corticomedullary junction; as the lesions become more extensive they extended through the entire cortex. In the liver. lesions were observed in all parts of the hepatic lobule. The results of this study indicate that dimethylpolysiloxane fluid is deposited in the spleen, liver, adrenals, pancreas, ovaries, abdominal lymph nodes, and kidneys of mice when given by intraperitoneal injection of small amounts or by subcutaneous injection of large amounts, 7-8 ml. Smaller subcutaneous doses, 1 ml. of liquid silicone in the same animal species occasionally causes similar lesions which occur only in the sona reticularis of the adrenal glands." "The mechanism of absorption and systemic distribution of silicone fluid in mice is still unknown. Venous embolism or phagocytosis with distribution in the reticuloendothelial system seems to be likely possibilities. Most visceral lesions did not occur prior to three months following injection except in isolated instances. This delay seems to implicate the reticuloendothelial system as being the most likely method of transfer."

CITE: KMM 31074 - 31087

Document #69
09/06/66
MISCELLANEOUS - ORGANIZATIONAL SURVEY
Minutes of the Board of Directors' Meeting for Dow Chemical Company with a reference to a secrecy agreement with Dow Corning Corporation regarding the biological properties of silicones.

CITE: TDC 11625 - 11627, Exhibit to Bennett Deposition and to Julius Johnson Deposition.


Document #70
10/10/66
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - PRODUCT LABELING
TESTING

Memo from Don McGhan (at Dow Corning) to McIntyre with copies to Pellikka, Hutchison, Bennett, Burdick, Weiler and Diamond regarding "Biological Testing of 360 Fluid, Our Project No. 5152." Steve Carson of FDRL, Harry Dingman of Dow Corning's legal staff, and McGhan "strongly suggest" that Dow Corning not proceed with biological testing of Dow Corning 360 fluid in containers smaller than 440 pounds. McGhan asks McIntyre to "review your marketing objective for 360 Medical Fluid and determine if biological labeling and certification is required in container sizes smaller than 440 lbs. in order to increase sales of the product."

CITE: KKA 7168, Exhibit to D. McGhan Deposition

Document #71
10/12/66
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - SALES
STERILIZATION/CONTAMINATION
TESTING

"Chemical Research Progress Report (Restricted), Report No. 2964," by R. McCarty and J. Speier - all of Dow Corning. Dr. Hunter established a committee of Bennett, Hobbs, McCarty, Stark, Weyenberg and Speier to isolate and identify a pharmacologically active substance believed to be present in DC 555 fluid.

Silanols are referenced on DCC 281002126 - 281002126 - they are "profoundly toxic" and have effect as a CNS depressant. Silanols have been under study since 10/65. There is a reference to the Mellon Institute on DCC 281002127. Also note that Dow Corning was using Dow Chemical's animals and testing facilities.

CITE: DCC 281002121 - 281002162, Exhibit to Bennett Deposition, Exhibit to McHard Deposition, Exhibit to Ryan Deposition, Exhibit to Isquith Deposition and Exhibit to LeVier Deposition. WITNESS: Bennett (ancient document exception to hearsay). DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare.

Document #72
01/10/67
ACKNOWLEDGEMENT OF NEED FOR TESTING
TESTING

Rowe memo to McHard with copies to Bennett, Dingman, Heuerman, and Hunter. This memo is in reply to the 12/16 memo from McHard on Product Safety. Rowe has looked over the IBT testing outline and feels that "in general, (it) contains the type of information I believe is necessary. However, I do believe that some of the work which has been listed should be done at an earlier stage and a minimum of liability." Rowe gives advice on the types of tests and the timing of the necessary tests in his critique of the IBR testing plan. Further, "I also have my doubts about the wisdom of selling the material, even though it is intra-state, before you at least have long-term studies going, and the data indicates no likely hazard. I realize that intra-state sales can be made without FDA approval, but nevertheless, if you were challenged, I fear that you would have difficulty in convincing any court that you had acted in a responsible way even though you might be within the limitations of the Federal Food, Drug, and Cosmetic Act." He states that he will be happy to discuss any of these matters further with McHard.

CITE: DCC 281041120

Document #73
02/01/67
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Minutes of the meeting of the Executive Committee. Includes notes regarding a joint agreement with The Dow Chemical company pertaining to certain silicone products designated as DC-555, DC-555A, and compounds derived from and related thereto, and a joint development agreement relating to the physiological effects resulting from ingestion or injection into the systems of animals and men of particular physiologically active silicones.

CITE: DCC 1010001438 - 101001440, Exhibit to Bennett Deposition, Exhibit to LeBeau Deposition, Exhibit to Rowe Deposition, Exhibit to Caldwell Deposition, Exhibit to McHard Deposition, Exhibit to Julius Johnson Deposition, and Exhibit to LeVier Deposition.

Document #74
02/08/67
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE

"Report to Dow Corning Corporation Rabbit Teratogenic Study, TX-114," by Industrial Bio-Test Laboratories. Nine test groups consisting of fifteen pregnant does were used in this study. It appears that TX-114 produces no adverse effect upon maternal growth or upon the ability to carry the reproduction process successfully form six to eighteen days inclusive. The number of resorption sites noted appears to be proportional to the total amount of material administered. It is felt that this reflects system damage to the maternal organism which obscures the secondary effect upon the developing fetal system. At a level of 200 mg/kg subcutaneously, slight alterations (clubbing of extremities and umbilical hernias) were observed in proportions which approach the upper limits of an expected non-treatment group. "(I)t is felt that the material is non-teratogenic. However, the incidence of abnormalities seen at lower levels, especially 200 mg/kg, would lead to a conclusion that the teratogenic potential of the material should be investigated in at least one other species and possibly in another rabbit strain." Eldon Frisch, Dow Corning, in a 12/331/87 document, claims that this study was inconclusive. "(C)lubbing of extremities and umbilical hernias were near the upper limit...."

CITE: I 661 - 702. DUPLICATE: KMM 115833 - 115873; (Referenced in KMM 407480 - 407482). NOTE: See 12/31/87 entry in Master Timeline.

Document #75
02/16/67
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

"Discussion Of Toxicology Of Various Dow Corning Products." A meeting was held on 02/16/67, present were Steve Carson (FDRL), Fancher (IBT), V.K. Rowe (Dow Chemical), Bennett, Boone, Braley, Bennett, Dingman, Hobbs, Hunter, Don McGhan, McHard and Radzius. They discussed the IND's on file with the FDA including the IND for burned hand, the silicone injection IND, the bladder treatment IND, applications for Silastic rubber dental liner and dental impression material such as permanent tooth implants using Silastic rubber to anchor tissue contact material, implant testing on new or modified formulations, corneal implants, in-dwelling catheters, needle and syringe treatment, DC 360 medical fluid, elastomer for coating pacemakers, comparison of the reproductive studies carried out at FDRL including the findings of club footing and resorption as a result of the treatment, DC FS-1265 fluid and foot and hand protector products ("A recent report as a result of a one-year feeding in rats did seem to show a dose-related effect on testis and accessory sex organ weight but V.K. Rowe thought that because of the species difference and the time involved in the test and the fact that the test was oral and not dermal and since all of the dermal data looked good, there should not be any reason to suspect this product" (DCC 281041880), and tests on Dow Corning 555 fluid and 360 medical fluid.

A discussion was also held on the different viscosity grades of "Dow Corning 200 fluid or Dow Corning 360 fluid" compare with regard to polymer size distribution. Although higher viscosities show broader distributions, "there appears to be almost as much of the lower polymer ends in the 350-centistoke" as in the lower viscosities. (DCC281041877). The agenda is located at 281041882.

CITE: DCC 281041877 - 281041882, Exhibit to Bennett Deposition, Exhibit to McHard Deposition, Exhibit to Rowe Deposition, and Exhibit to LeVier Deposition.

Document #76
03/10/67
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

"Summary of Toxicological Testing of Dow Corning FS-1265 Fluid and Ointment, Foot Protective" by "jar" (Joseph Radzius). It was reported to the FDA in June 1966 that Phenylmethyl polysiloxane - DC 555 fluid - exhibited biological activity, i.e., a depressant effect on spermatogenesis and a reduction in testicular size. Dow Corning elected to withdraw the product from the market. Very recently Dow Corning received a report from FDRL on a 12-month oral administration of FS-1265 fluid in rats which also showed a dose-related spermatogenic arrest, depressed testicular and seminal vesicle size similar to that observed for 555 fluid. Thus, this fluid also exhibits biological activity.
CITE: DCC 281041861 - 281041863

Document #77
03/14/67
TESTING

Dow Corning study titled "Biologically Active Organosilicon compounds, Report No. 3035," by McCarty, Lee and Burk. Test data on 83 organosilicon compounds which have proved active in biological screens. The activity listed includes anti-cancer, anti-malarial, anti-echistosomasis, anthelmintics, soil bonding agents, premergent herbicides, post-emergent herbicides, anti-coccidiosis, fungicides and bactericides, contact insecticides, fumigants, anti-crusting agents, and general pharmacological screen in which the compounds were examined for use in drugs. Dow Chemical does the screen on agricultural, animal science, solvent stabilizers, etc. on these compounds.

CITE: DCC 281002231 - 281002247, Exhibit to Tyler MDL and Harris County Depositions, Exhibit to Bennett Deposition, Exhibit to Ryan Deposition, Exhibit to Julius Johnson Deposition, Exhibit to Himnam Deposition, and Exhibit to LeVier Deposition.

Document #78
03/21/67
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

S. Carson, Food and Drug Research Laboratories, issues report entitled "Summary of Histopathological findings in Primates." Findings include cystic spaces with vacuolated cell and a few foreign body type cells in soft tissues and around minor salivary gland tissue and skeletal muscles, cystic spaces with vacuolated cells and foreign body type giant cells in both breasts, acute necrotizing pneumonitis in the lungs, similar changes in the submaxillary gland, degenerative changes in the kidneys, pleural fibrosis and edema in the lungs, small and large cystic spaces in the dermis and subcutaneous tissues, focal calcification in the adrenal glands, chronic stomach inflammation, and chronic phclonephritis in the kidneys. Include letter sent from F. Ashley to S. Carson dated 12/02/66 enclosing pathological slides showing area and amount injected and the autopsy date of the animal. Includes letter from S. Carson to S. Sternberg dated 01/04/67 enclosing slides prepared from tissues of sumi apes sent by Dr. Ashley; a member of the Silicone Injection Committee of the Dow Corning Corporation (Carson and Food and Drug Research Laboratories are consultants for Dow Corning Corporation). Carson writes:

"The tissues which Dr. Ashley submitted together with information regarding total volumes injected and the date of the last injection (copy enclosed) represent some of the most critical tissues available in the United States since they involve between two and three years of chronic study....This material represents the closest parallelism to human experience that we have been able to obtain in any animal studies to date.

... We have mentioned that this material is precluded from use in mammary tissue augmentation. However there is a considerable black market in a Japanese product which contains a similar silicone fluid with some type of oil."

CITE: T 822 - 832, Exhibit 107 to Harris county Rathjen Deposition. DUPLICATE: F 316 - 326.

Document (On PLAINTIFF'S LITERATURE LIST)
(this is between #78 & #79)
04/00/67
(ON PLAINTIFF'S LITERATURE LIST)

F. Ashley, S. Braley, T. Rees, D. Goulian and D. Ballantyne author "The Present Status of Silicone Fluid in soft Tissue Augmentation" published in Plastic and Reconstructive Surgery, Vol. 39, No. 4, 411-420. The clinical use of silicone liquids in man preceded any responsible and controlled experiment in animals. The unresolved problem related to silicone is migration to distant organs, cautioning against its use for mammary augmentation. The authors report one case of unnecessary force during the injection of silicone that may have caused blindness in one patient by possibly disrupting the arterial or venous system. They also caution against using silicone fluid with any additives such as olive oil.
CITE: PSC Medical Articles CD, J 157 - 166

Document #79
04/28/67
GEL MIGRATION
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

"Reproduction Study, Albino Rats, TX-114, Dow Corning Tox. File No. 1059-5" conducted by Industrial BIO-TEST Laboratories, Inc. and sponsored by Dow Corning Corporation. PDMS, 350 cs., was tested for its effects on fertility, reproductive performance, embryongenesis and perinatal and postnatal performance in rats and rabbits. Albino rats given up to 1000 mg of TX-114 per kilogram of body weight daily by subcutaneous injection show normal growth patterns, have the desire to mate and the ability to conceive, carry the reproduction process to parturition and are able to successfully nourish the resulting progeny. The offspring are free of external and internal malformations and are judged to be normal as indicated by both normal survival indices and progeny body weights. Treatment with TX-114 from implantation through the completion of organogenesis did not produce teratogenic effects in the rat. Lactation, measured in rats by dosing parental animals from the end of fetal organogenesis through the lactation period, was unaffected by daily subcutaneous administration of TX-114.
CITE: P 13605 - 13611

Document #80
04/28/67
KNOWLEDGE OF LIQUID SILICONE DANGERS
TESTING
TISSUE REACTION

"Studies of the Effects of Dow Corning 360 Medical Grade fluid (MDX-4-4011) on Reproduction in Rats and Rabbits" conducted at Food and Drug Research Laboratories and sponsored by Dow Corning. This polysiloxane compound was subcutaneously administered to rats and rabbits. One significant effect is a dose-related incidence of in-utero mortality at 200mg. and 1000 mg. during the third trimester of rat pregnancy. (FDA 26359 - 26377: T001064 - 001103). Eldon Frisch, Dow Corning, in a 12/31/87 document claims that this study was inconclusive. The fetuses of some rats had "slight increase in frequencies of incomplete developed sternebra and incomplete closure of cranial bone. Some rabbits in the FDRL study had slightly higher in utero mortality."
CITE: T 1064 - 1103 (Referenced in KMM 407480 - 407482).
NOTE: See 12/31/87 entry. DUPLICATE T 996 - 1029.

Document #81
07/19/67
MISCELLANEOUS
SILICA STERILIZATION/CONTAMINATION
"Dip Coated Mammary", project no. MD-50 by P. Lange, L. Crusen. This report constitutes the final phase in the transfer of Medical Development Project No. 50, dip Coated Mammary, to the Medical Products Plant. This report contains the raw material specifications, formulations, manufacturing procedures, formulation specifications and the dip coating procedure and specifications.
CITE KMM 320434 - 320454.

Document #82
08/17/67
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - PRODUCT LABELING
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD


Women's Wear Daily article titled "Dow Corning Indicted on Breast Expanding Fluid." charges include illegal distribution and improper labeling of Medical Fluid 360. It is charged that the labeling failed to include adequate directions for use and adequate safety warnings. The indictment also charges that the drug had not been approved by the FDA and had not been exempted from the normal requirements of the Food, Drug and Cosmetics Act.
CITE: GEG 8984 - 8986.

Document #83
10/18/67
TESTING

J. McHard, Dow Corning, memo to I. Hutchinson, Bennett, Dingman, Hunter and Don McGhan describing the policy in the toxicological evaluation of Silastic silicone rubber for implant use. It involved a two year implantation in dogs with one interim sacrifice in six months. Providing there was no toxicity and tissues looked normal, marketing could begin after six months. Based on recent information from the Medical Products Division, he believes that Dow corning is not strictly adhering to its toxicological evaluation policy. CITE: KMM 337147

Document (NOT ON PLAINTIFF'S EXHIBIT LIST)
(this is listed between #83 & #84)
10/30/67
(NOT ON PLAINTIFF'S EXHIBIT LIST)

Hobbs, Dow Corning, memo to H. Dingman, Hutchison, Don McGhan, McHard, and Pellikka regarding "Minutes of Meeting Held October 27, 1967." The meeting was held at the request of Hutchison: "to discuss toxicity testing of SILASTIC implants and more specifically the penile implant.

Ira expressed his feelings relative to the necessity of 2-year toxicity studies on new materials in dogs. In general he feels the 2-year study is not necessarily due to the absence of carcinomas being produced when foreign bodies have, through the years, been implanted into the human body. Ira did feel the 2-year data would be advantageous to have on record in case of product liability and also if and when the FDA assumes the regulation of devices.

J.A. McHard expressed the recommendations of the Product Safety Committee based on advice from various Dow Corning consultants, i.e., Steve Carson, V.K. Rowe, Joe Calandra and (illegible). This recommendation is that new SILASTIC (illegible). This recommendation is that new SILASTIC (illegible) to be used for long-term implants shall have a 2-year carcinogenicity study in dogs. Preliminary marketing could begin after the testing had progressed six months if tissues are normal."
CITE DCC 204001107 - 204001108.

Document #84
11/10/67
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION
SILICA

Hobbs and Himmelsback memo to Barry, Bennett, Clark, Fenn, Greenhalgh, Hansen, Hargreaves, Hedlund, Hunter, Hyde, Donkle, C. Lentz, Maneri, McHard, Nelson, Quinn, Ragborg, Ringey, Stinton, Tyler, Weyenberg and Zeman regarding "Status of the Toxicity and Industrial Safe Handling of J-DCA." J-DCA is Dow Corning Silica A; results from a recent study indicate that under certain conditions, exposure to this "will cause significant change in the links."
CITE: DCC 281041072 - 281041074.

Document #85
12/15/67
KNOWLEDGE OF LIQUID SILICONE DANGERS
TESTING
TISSUE REACTION

Food and Drug Research Laboratories issues its report to Dow Corning Corporation, "Studies of the Effects of Injected Dow Corning 360 Fluid In Dogs." Fifteen beagles were subcutaneously injected with Dow Corning 360 fluid in the scapular region for ten successive days. There was a shifting of the injected mass, signs of mange, fluctuations in weight, elevations of the hemoglobin concentrations, differentials in the leukocytic counts, congestion and changes in all organs. One of the beagles died with congestion of the liver, kidneys and heart accompanied with hemorrphagic changes in the lungs and the adrenals.
CITE: T 1202 - 1209, Exhibit to Petratis Deposition. DUPLICATE: T 1251 - 1302; KKH 8185 - 8290; FDA 33172 - 33227; F28 -79.

Document #86
01/04/68
MISCELLANEOUS - ORGANIZATIONAL SURVEY

Minutes of the Board of Director's Meeting of Dow Chemical Company with a reference to loans and advances made to Dow Corning Corporation.
CITE: TDC 11702 - 11703, Exhibit to Bennett Deposition, and Exhibit to Julius Johnson Deposition.

Document #87
02/20/68
KNOWLEDGE OF LIQUID SILICONE DANGERS

Bureau of Regulatory compliance reports on the prosecution of Dow Corning, Bass, Rhodes, and McIntyre for selling a new drug - Dow Corning 360 Fluid - without an approved New Drug Application.
CITE I 470.

Document #88
02/28/68
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Steve Carson, Food and drug Research Laboratories, issues a Supplement to the Report on "Studies of the Effects Of Injected Dow Corning 360 Fluid 350 cs In Dogs. " Following a single subcutaneous injection, silicone was transported to all organs via the lymphatic or vascular network.

"(D)espite parenteral route of administration, C(14) (DC 360 Fluid) was present in the gastrointestinal tract, in the aorta and apparently in the lymphatic pathways as evidenced by the lymph nodes, and salivary glands, thus suggesting that transport and distribution in these animals was via the vascular system, the lymphatic, and recirculation via the bilary tract."

Distribution occurs throughout the entire body with no apparent concentration in any specific organ. In Dow Corning's Toxicology Report Reference 99, Dow Corning's abstract states, "The distribution of radioactivity was ubiquitous with evidence of greater activity in liver, spleen, kidneys, heart, lungs and brain.

CITE: T 38842 - 38866, Exhibit 3 to Harris County Rathjen Deposition. DUPLICATE: KKP 16422; FDA 26696 - 26701; I 1333 - 1341; KKP 16422 - 16431; M 100145 - 100154.

Document #89
03/07/68
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Minutes of the Board of Directors' Meeting of the Dow Corning Corporation with reference to the officers of Dow Corning being approved to sell to Dow Corning employees common stock in the Dow Chemical Company. The minutes also refer to an agreement between Dow Corning and Dow Chemical for joint research, development, evaluation and commercialization programs on the physiological effects of organosilicon compounds.
CITE: DCC 101001529 - 101001543, Exhibit to Bennett Deposition, Exhibit to Julius Johnson Deposition.

Document #90
04/22/68
TESTING
TISSUE REACTION

"Histopathological Findings In Animals of Various Species from Experiments conducted by Thomas D. Rees" is prepared S. Carson and Food and Drug Research Laboratories for Dow Corning Corporation. Findings using mice include various tissue reactions in the liver, spleen, kidney, fat, adrenal glands, pancreas, ovaries, uterus, endometrium, lymph nodes, small intestine, and stomach. Findings using rats include various tissue reactions in the fat, spleen, kidney, pancreas and adrenal glands. Findings in guinea pigs include various reaction in the fat, kidney, pancreas, adrenal glands, spleen and liver. Findings using hamsters include various tissue reactions in the fat, spleen and kidneys.
CITE: T 1467 - 1528

Document #91
04/26/68
ACKNOWLEDGEMENT OF NEED FOR TESTING
CONCEALING FROM FDA
MISCELLANEOUS - LOBBYING
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Rowe, Dow Chemical, letter to Goggin, the new President of Dow Corning (who was recently transferred from Dow Chemical), regarding Dow Corning's need to establish its own toxicology laboratory. Rowe states that Dow corning has a "poor image" with the FDA which is "partly deserved, partly undeserved." He suggests that Dow corning needs a "change in philosophy" to turn its image around. He writes:

"Respect in Washington or elsewhere cannot be acquired except by earning it through demonstrated competency, integrity, and an open willingness to cooperate. I have had the feeling at times in the past that these desirable characteristics have not always been apparent, in fact, it has seemed to me that there has been a reluctance to deal openly with the FDA. An antagonistic approach toward the FDA usually, in my experience, results in a reaction on their part which, sooner or later, becomes apparent in one form or another and will be regretted."

(p. 1) Rowe recommends that Dow Corning create a position entitled "Director of Government Regulatory Relations" to interact with the FDA and help Dow Corning's image. He also recommends that Dow Corning Establish a toxicological laboratory in-house so that they are able to "know and understand the physiological properties of all such materials." (p. 6) The Dow Corning laboratory should be patterned after the Dow Chemical laboratory. Rowe recommends Dow Corning hire Ken Olson of Dow Chemical for this position. He also explains that:

"It appears to me that one of the most important areas for toxicological study of DC materials, particularly those designed for use in or on human beings, is that which may be called biochemical. By this I mean studies which will completely describe the fate of materials applied to, or administered to, the intact living organism including animals and plants." (p. 9)

CITE: DCC 410000031 - 4100000040, Exhibit 2 to Bennett Deposition, Exhibit 1 to LeBeau Deposition, Exhibit 6 to K. Olson Deposition, and Exhibit to Rowe Deposition.

Document #92 & #93
05/23-24/68 (this is listed as #92 & #93)
ACKNOWLEDGEMTN OF NEED FOR TESTING
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Minutes of Meeting at Midland on May 23-24, 1968 with representatives form Dow Corning, Industrial Bio-Test, Food and Drug Research Laboratories, and the Dow Chemical Company." Attending were Bennett, Calandra (IBT), Carson (FDRL), Bennett, Frisch, Hobbs, Hunter, Hutchison, McHard, Radzius and Rowe, Dow Chemical. The subject of the meeting was a "Toxicology Review of Dow Corning Products."
CITE: DCC 281041054 - 281041059.

Document #94
05/31/68
TESTING
TISSUE REACTION

FDA: "Informational Materials Supplied To clinical Investigators" provided to the FDA sponsored by Dow Corning corporation for Dow Corning 360 Medical Fluid 100 Centistokes (as used for the immersion of burn victims). The purpose of this study is to evaluate continual immersion therapy as a treatment modality in the management of the burned patient. The fluid in which the patient is to be studied is Dow Corning 360 Medical fluid of a viscosity of 100 centistokes. Dow Corning 360 Medical Fluid (MDX-4-4066 Fluid) is a dimethylpolysiloxane fluid and is identical to the product known to FDA scientists as Dow Corning 200 Fluid except that more rigid quality control procedures have been established for the medical grade product.

This fluid had been tested on pigs, monkeys, rabbits and dogs at Food and Drug Research Laboratories. Observations were made of the effects of administration to rabbits and rats of diets containing 1% Dow Corning 360 Medical fluid, 50 or 350 centistokes, for eight to twelve months, respectively. These were compared to effects resulting from administration of the basal ration alone. No significant differences were found between the groups receiving the polysiloxanes and the basal control in growth or any of the parameters of physiological function, organ weight, or tissue morphology.

Clinical experience with silicone immersion has included the immersion treatment of thirteen healthy unburned control vs. eighteen burned victims and the immersion treatment of one patient suffering from toxic epidermal necrolysis. Results indicates that silicone immersion is contraindicated in burn cases with open-chest injuries and/or venous cutdown on the leg. Continued immersion is contraindicated if sever skin rash develops which does not resolve with adequate skin hygiene and/or rigorous quality maintenance of the silicone fluid.

Immersion may precipitate or increase hallucination. Immersion results in external fluid pressure on the chest which may produce sufficient splinting effect to reduce chest motion and prevent adequate aeration of the lungs in those patients who are debilitated or who have chest injuries. Intermittent positive pressure breathing may be required in these cases to enhance aeration of the lungs.

Skin rash has been observed in immersed patients. Severe and persistent skin rash which does not resolve with adequate skin hygiene and quality maintenance of the fluid is adequate reason to terminate immersion.
CITE: KMM 104968 - 105041.

Document #95
06/03/68
COHESIVENESS - LIQUID COMPONENT OF GEL
GEL MIGRATION
TESTING

Dow Corning completes a study of the biological distribution of dimethylpolysiloxane in adult male mice. Significant amounts of radioactivity were found in the tissues and body fluids analyzed. The level of absorption and the biological distribution of the radioactivity were not dependent upon the molecular weight distribution of the fluid or the method by which the fluids were administered.
CITE: DCC 281001381 - 281001399, Exhibit to Harris Country LeVier deposition, Exhibit 3 to Harris Country Rathjen Deposition, Exhibit 19 to Harris County Zahalsky Deposition, Exhibit to Harris County Tyler Deposition, and Exhibit to Weyenberg Deposition. DUPLICATE: M 100155 - 100174; DCC 242031103 - 242031121; FDA 43184 - 43202.

Document #96
07/16/68
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE

FDA: Dr. Wilson writes a letter to Dr. Inscoe of the FDA regarding his analysis of the reproduction studies done on Dow Corning Medical Fluid 360 by Food and Drug Research Laboratories. He states that the reports "were not presented in such a way as to inspire complete confidence...." He also concludes the compound causes an "appreciable increase in fetal death and resorption in rabbits" which is dose related and also causes an increase in malformations in rabbits at certain doses. Thus, "the compound under consideration cannot be declared to have no teratogenic potential."
CITE: KMM 128723 - 128724.

Document #97
08/08/68
GEL MIGRATION
TESTING
TISSUE REACTION

FDA: The FDA recommends that Dow Corning's IND 2702 remain ineligible for reinstatement because of the lack of toxicity information, deficient protocols and the lack of declaration that the IND has no teratogenic potential. The FDA directs Dow Corning to provide data on the metabolic fate and migratory sites of silicone, including studies on the kidney and liver.
CITE: FDA 28545 - 28547. NOTE: See 09/24/68 entry.

Document #98
10/09/68
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Hobbs, Toxicologist at Dow Corning, letter to Dr. Charles Riffkin, The Squibb Institute for Medical Research, responding to his inquiry about the distribution and fate of injected silicones. He encloses the study, "Studies of the Effects of Injected DOW CORNING 360 Fluid, 350 cs., in Dogs," stating:

"The results of this study indicate that distribution occurs throughout the entire body with no pronounced concentration in any specific organ. It is evident by the preliminary nature of this study that the fate and chemical nature of the material after it vacates the injection site is unknown

CITE: FDA 27154 - 27155, Exhibit to K. Olson Deposition.

Document #99
10/17/68
FRAUD/MISREPRESENTATION
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - PRODUCT LABELING
TESTING

Olson memo to Pail with copies to Bennett, Currie, Gergle, Hobbs, Hunter, McHard, Radzius and Vaughn regarding "Suitability for Industrial Use of Protective Hand Cream Formulated with Dow Corning FS-1265 Fluid Unstripped of Cyclic Trimer." The Dow Corning Toxicology Department recommends the use of Protective Hand Cream, industrially, does not pose a significant hazard, and "represents an appropriate risk for Dow Corning." Olson reviews the studies to date on FS-1265 Fluid including studies by IBT - 20 day subacute dermal study in rabbits (spermatogenic depression was found to be mild to moderate in the controls and not significantly different in the test groups); one-year dietary feeding study in rats ("There was evidence of decreased spermatogenesis in the male test animals"); IBT - 14 week dermal toxicity in rhesus monkeys (biopsies at 30-days showed testicular hypoplasia); Dow Chemical (cyclic trimer possesses a relatively high acute oral toxicity); and IBT - acute percutaneous absorption study. He recommends industrial use of Protective Hand Cream containing less than 15 p.p.m. of cyclic trimer and that this is an appropriate risk. "We wish to emphasize that the front label flagrantly (sic) misrepresents the product from an efficacy viewpoint. All data generated to date shows, unequivocally, that the cream does not protect against the irritating properties of the chemicals studied. Ethically, such advertising leaves much to be desired and is frowned upon by government agencies and all who are charged with matters pertaining to consumer protection and proper representation"
CITE: DCC 218041771 - 281041776, Exhibit to K. Olson Deposition, and Exhibit to LeVier, Deposition.

Document #100
11/29/68
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

Steven Carson, Food and Drug Research Laboratories, issues a report on "Chronic Implantation Studies of Polysiloxanes In Dogs" contracted by Dow Corning. The report states:

"Chronic implantation studies were conducted in dogs over a three year period utilizing a variety of polysiloxane materials. When possible comparisons were made between solid and perforated wafers of individual materials implanted into intramuscular, subcutaneous and intraperitoneal sites. The number of implants utilized, provided for microscopic examination of replicate tissues at each time period, i.e. 3, 9, 24, and 36 months.

Inasmuch as each type of polysiloxane was evaluated independently no direct comparison between materials is provided, however the physical forms of each were compared. It may be concluded that in every instance the degree of reaction about the perforated implants was less intense than that associated with the solid implant, particularly with respect to the degree of fibrous reaction or extent of hyalinization or inflammatory cell reaction.

Samples of polysiloxane materials 370, 372 (including Cronin breast), fine and coarse sponge, silphenylene and LS each involved samples in which the physical form of the implant was the major variable. In the instance of the sponge implants (coarse and fine), a somewhat more intense connective and fibrous tissue reaction was observed with fine sponge in the initial 9 month period but lessened markedly at 24 and 36 months. The prosthetic breast samples with 372 revealed no untoward tissue reactions. Comparison of cured and uncured samples 386, 382, 5392, X-3-0855 and Medical Adhesive Type A generally revealed a more severe inflammatory cell reaction at 3 months in the uncured samples of 386, 5392 as compared to the cured samples. This reaction was absent at 24 and 36 months. The Medical Adhesive Type A differed, in that the initial tissue reactions were minimal in each.

Generally, no untoward chronic tissue reactions were noted with any of the implant materials. Systemic tissue responses were not observed at 24 or 36 months. There was no evidence of tumorigenesis, with any of the samples or at any of the sites of implantation over a 3 year period of testing in dogs."

The first page of this report states that "this report is not to distributed outside Dow Corning Corporation."
CITE: T 2033 - 2096, Exhibit 35 to Bennett Deposition (used by Dow Corning), Exhibit 29 to MDL
Rathjen Deposition (used by Dow Corning), and Exhibits 19 and 20 to Zahalsky Deposition. DUPLICATE: FDA 27384 - 27409.

Document #101
01/29/69
SHELL STRENGTH - THICKNESS
RUPTURE

G. Robertson, Dow Corning, memo to Koning regarding a mammary implant ruptured 1 1/2 years after implantation which was returned by Dr. Crosby. Robertson states, "(T)he envelope edges adjacent to the rupture, appeared to be of a very low tear strength. The physical properties of this envelope may never have been adequate." (emphasis added).
CITE: KKH 1654

Document #102
03/24/69
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE

Dr. Franklin Ashley, a clinical investigator for IND 2702, writes to Dr. Frank McDowell regarding an article by Bishoff and Bryson on the carcinogenicity of silicone in fluid in rats and mice. Braley, Dow Corning, has reviewed the article and has stated to Dr. Ashley that:

"According to what he says, and he would not want to say this to you, he feels that this article is well written and should not be published. I agree."

CITE: OOM 320814.

Document #103
06/10/69
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Memo from Olson to Frisch with copies to Bennett, Hobbs, Hunter and Radzius regarding "Telephone Communication with Dr. John Wilson of Johnson & Johnson." Dr. Wilson, toxicologist at Johnson & Johnson, was contacted by telephone regarding their subacute dermal rabbit study on Dow Corning 556 and 360 fluids and Dow Corning MDDX-4-4122 wash resistant base. Dr. Wilson stated that the materials had been applied to rabbit skin daily. All animals showed a trend toward testicular atrophy. "There was a suggestion of dose-response relationship with Dow Corning materials although the effects were not statistically significant. A subacute oral rat study is in progress." Olson indicated to Wilson that Dow Corning would be concerned about positive findings with the second study and would be agreeable to meeting with them to compare their respective data.
CITE: DCC 281041112, Exhibit to McHard Deposition, Exhibit to K. Olson Deposition, and Exhibit to LeVier Deposition.

Document #104
07/15/69
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Food and Drug Research laboratories report on the findings in the chronic parenteral (intraperitoneal) study initiated by Dr. Ballantyne, Rees and Hawthorne at the NYU School of Medicine. After silicone fluid in the peripheral erythrocytes in early hematologic examinations was observed, Dow Corning transferred the study and its financial sponsorship from NYU to Food and Drug Research Laboratories. "When the animals received 51 cc and 62 cc of fluid, inflammatory cells were observed in the spinal meninges (which was not stated in earlier reports). Injections of large volumes of silicone produces wide spread deposition throughout the reticuloendothelial system, silicone vacuole accumulation in cells and a systemic distribution of silicone droplets.

CITE: T 2866 - 2945 (The study is referenced in FDA 26875 - 26889). NOTE: See 06/30/75 entry.

Document #105
08/06/69
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Isquith, Dow Corning Biomedical Research Laboratory, memo on the "Current Status of Microbiological research." Isquith states that:

"The main purpose of the survey is to help in establishing the basic relationship between organosilicon structure and biological activity, the further pursuit of which rests with our own secondary stage research activity into the physiology (metabolism, mechanism of action, site of action, etc.) of the compounds and a good screening procedure for identification of developmental potential. (DCC 16000004)

Another area for research is the development of a biological assay for determination of organosilicone interferon induction. (DCC 16000004). Dow Corning has developed sufficient expertise in viral methodology to conduct the assay, but "there would be considerable advantage in using such a system (more stable virus, greater lethality) as is currently being employed in a survey for interferon inducers at Dow (Chemical) Human Health by Dr. N. Miner...." (DCC 16000005) He recommends using Dr. Miner's lab for seeking a long lasting interferon inducer among organosilicone compounds. (DCC 16000006)

Finally, another area is the "Investigation of Physiological Effects of Some Organosilicon Compounds." (DCC 16000011). Isquith concludes that the area of microbiology in relation to organosilicon chemistry "is mushrooming at a pace that even now we are unable to adequately provide this cover. A wise investment at this time would be the hiring of a virologist (M.S. preferably) with training in tissue culture, virology, and immunochemistry. I have not had time to investigate thoroughly, but feel there is a good chance for development of possible potential in the areas of hypersensitivity, graft rejection, and autoimmune disease (arthritis, glomerulonephritis, etc.) which should be within the scope of a person with the training I suggested." (DCC 16000014)

CITE: DCC 16000002 - 160000014, Exhibit 2 to Isquith Deposition, Exhibit 3 to D.McGhan Deposition, Exhibit to Blocksma Deposition (used by plaintiffs and Dow Corning), Exhibit to LeBeau Deposition, Exhibit to Bennett Deposition, Exhibit to Boley Deposition, and Exhibit to Julius Johnson Deposition WITNESS: "Bennett (Authenticated in Isquith, Vol. I, 119-120).

Document #106
08/14/69
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Letter of agreement between Dow Chemical Company, Dow Corning Corporation and Lepetit SpA for a joint development program regarding the biological activity of organosilicon compounds. The agreement requires the full disclosure of all proprietary and confidential information of each party to the agreement to each other party.
CITE: TDCH 1275 - 1276.

Document #107
11/15/69
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Doremire memo to Bennett regarding chemical warfare and riot control agents, XZ8-3063. This is a silicone glycol. It goes through the skin as if there was no skin there. "Do you have any suggestions for a chemical that could be added to XZ8-3063 which would cause a variety of effects? These effects could vary from a drug that would act as a simple tranquilizer to a drug which would cause a loss of consciousness." In the case of riot control, the drug might be effective for 1/2 hour whereas a chemical warfare use might need 2-4 hours effectiveness. He plans on checking with the "Analytical Laboratory on toxicity information.

CITE: DCC 281014081, Exhibit 3 to Harris County LeBeau Deposition, Exhibit to Rowe Deposition, Exhibit to Bennett Deposition, Exhibit to McHard Deposition, and Exhibit to Ryan Deposition.

Document #108
00/00/70
00/00/71
00/00/72
FRAUD/MISREPRESENTATION

Dow Corning advertisement; "New sterile package provides Silastic Mammary Prosthesis ready to implant. This convenient, sterile blister pack assures greater product reliability, eliminates excessive handling and can be easily opened with scissors." It also includes references to sizing rings and that the mammary implant no longer is fitted with fixation patches.
CITE: M 700003; M 700008 - 700009. DUPLICATE; M 370049 - 370052; M370108 - 370109; M 370113 - 370114; KKH 62679 - 62682; M 700019 - 700020.

Document #109
09/20/76

Hobbs, Dow Corning, memo to Hinsch with a copy to Lentz regarding information concerning migration of silicone gels. Hobbs states that experimentation had not demonstrated migration of Dow Corning mammary gel but this factor does not appear to be true for all silicone gels. Hobbs further states that gels having a low consistency due to low levels of cross-linker appear to migrate along tissue planes in much the same manner as large injected doses of silicone fluid.
CITE: M 170104, Exhibit 130 to Burda Deposition; Exhibit 91 to Braley Deposition. DUPLICATE: M 570060. NOTE: The document was listed as 00/00/70 on Plaintiff's Trial Exhibit List.

Document #110
01/12/70
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

Silas Braley, Dow Corning, memo to various Dow Corning employees distributing interim research report on the investigation of Dimethylpolysiloxane Fluid Injections at the Institute of Reconstructive Plastic Surgery, New York University. The interim report states that "our most interesting recent findings indicate that in both mice and rats, injection of large volumes of liquid silicone, either interperitoneally or subcutaneously, in multiple injections, apparently produces a wide spread deposition of this material throughout the reticuloendothelial system. A more recent finding of some interest is that there is an apparent accumulation of silicone vacuoles both within the red cells and the leukocytes of the peripheral blood in mice and rats, which appears about one to three months after injection and persists for several months." The NIH grant will run out in about one year and these studies will have to be terminated. "It is our feeling that the evidence of systemic distribution of silicone droplets or vacuoles can not necessarily be considered an adverse effect, but is more likely related to total dosage. The dosages employed in animals rarely can be achieved in man with the possible exception of breast injections...."
CITE: T 2881 - 2885. NOTE: The report itself was an Exhibit to the K. Olson Deposition (KKH 9841 - 9845). This document also has the Bates number OOM 321368 - 321672 on it.

Document #111
02/02/70
STERILIZATION/CONTAMINATION

J.H. Wetters, Dow Corning Medical Products Plant, Report No. 229 to Burdick with copies to Reilly, Mantle, Piper, Don McGhan, Houle and Robertson regarding "White Particle Contamination of the Mammary Gel." The major contaminant was found to be crystalline by microscopy and potassium chloride and potassium bicarbonate by x-ray. Wetters cannot explain the presence of potassium bicarbonate. The white poly lined can in which it is contained could possibly be the source of this material.

J.P. Fitzgibbon feels that the crystalline potassium salts are the major portion of the contamination. "Gordon Robertson and Ken Olson should be contacted for an opinion as to whether these potassium salts are harmful." (MM 234057)
CITE: KMM 234056 - 234057.

Document #112
02/18/70
KNOWLEDGE OF LIQUID SILICONE DANGERS
ACKNOWLEDGEMENT OF NEED FOR TESTING
TISSUE REACTION

Report prepared Food and Drug Research Laboratories for the Dow Corning Toxicology department. There are relatively little specific experimental data available on the reactivity of biological systems to silastics and polymethylsiloxane (PMSs) fluids. Prior studies by other laboratories showed "significant testicular atrophy resulted" from topical application of a polymethylsiloxane fluid. In the present study, 15 applications of PMS fluid was applied topically on rats, guinea pigs, rabbits and dogs for a 20-day period, and was administered in the diets of rats and rabbits for eight months. In the rabbits that were topically applied with PMS fluid, "the reduction in the testicular weights of the PMS-treated rabbits is considered biologically significant."

In the rats that had PMS administered orally for one year, growth was retarded as early as the first week in feeding. The differences in weight gain between the test and control groups was "statistically significant" during the third week, with the weight gain in the test group lower than the control. In the female rats, there were "notable endocrine effects," smaller ovaries, enlarged pituitary, and increased weight in the adrenals and thyroids.

In the rabbits that had PMS administered orally for eight months, there was a "trend toward decreased testicular size in the test group...," a tendency toward lower hemoglobin and hematocrit in all rabbits in the test group, "some effect of PMS fluid on sperm maturation...," and testicular atrophy in the test rabbits.
CITE: T 2302 - 2341, Exhibit to K. Olson Deposition, and Exhibit to LeVier Deposition.

Document #113
02/19/70
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
SILICA

Dow Corning study titled "Acute Inhalation of 14C-Labeled J-DCA" (silica) by Hobbs and Lacefield finds that the acute inhalation of a relatively large amount of J-DCA appears to confine its residence and effect to the lung. The low levels of J-DCA found systemically is a strong indication that the acute adverse response is confined to the lung. This would also indicate the lung to be the target organ from a chronic exposure.
CITE: DCCF 5008903 - 5008907, Exhibit to K. Olson Deposition.

Document #114
03/02/70
KNOWLEDGE OF LIQUID SILICONE DANGERS
TESTING

D. Ballantyne letter to E. Hobbs, Dow Corning, answers questions about the investigation regarding dimethylpolysiloxane fluid raised by Hobbs' letter of 02/19/70. Current findings show an apparent accumulation of silicone vacuoles that were observed on the erythrocytes of rats only. He currently has studies underway on mice and baboons but the results are not substantial at this time. A research paper should appear in the April issue of the Reticuloendothelial Society.
CITE: T 2888 - 2889.

Document #115
04/13/70
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
RUPTURE
TISSUE REACTION

Olson memo to Boone with copies to Hunter, Hobbs, Koning, Radzius and Stark regarding "Inflatable Mammary Toxicology." He responds to Boone's memo stating, "The stability of dextran solutions in an implant situation over the long haul, particularly if there is diffusion of body fluids across the membrane would be difficult to accurately assess without biological data generated under use conditions. It is important to know these things prior to marketing. With my cursory knowledge of the problem I would tend to feel that such a device might cause some patients and Dow Corning some degree of grief. I would think that a rather extensive clinical investigation is indicated in order to assess benefit versus risk for Dow Corning."
CITE: KMM 146382-146384.

Document #116
04/14/70
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

"Two-Year Implant Studies with Silastic Materials in dogs" by S. Carson and Food and Drug Research Laboratories for Dow Corning Corporation. Carson states:

"A two-year study was undertaken to evaluate the effects associated with implantation of silastic materials into three sites of beagle dogs. Its purpose was to determine the tissue reaction and systemic effects associated with the implantation of silastic materials into subcutaneous, intramuscular, or intraperitoneal areas in dogs and to evaluate these responses to the implants with relation to time. No adverse findings were seen which could be associated with the implantation of the test materials. Fibrous capsule formation is the only histomorphologic change found in these animals. Capsule formation was of a 1 to 2+ thickness during the first six months of study and ranged from 2+ to 3+ thickness during the final examination after two years of test. In several cases, inflammatory cell reactions were also found. These were however anticipated, and were observed at the six-month and two-year sacrifice periods. The findings, therefore, are primarily associated with a minimal degree of foreign body reaction and no adverse systemic pathological manifestations are associated with the implantation of the silastic materials.

CITE: T 1529 - 1572.

Document #117
04/20/70
TESTING
TISSUE REACTION
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE

A study contracted to Food and Drug Research Laboratories by Dow Corning entitles "Two Year Studies with Miniature Silastic Mammary Implants TX-202A and TX-202"B in Dogs, Dow Corning Tox. File No. 1306-3" is sent to Dow Corning. In this study, one of the four dogs died and the three others had a chronic inflammatory response to the implants. While FDRL reports that the only adverse effects two years after implantation are fibrous tissue encapsulation and chronic inflammation, the attached chart (Table 3) shows reactions at 6 months of "large granulomatous mass adjacent to capsule" and "liver and kidney-congested." Dow Corning submitted this study, with the incorrect chart (Table 3) as part of its PMA Double Lumen Silastic II and Silastic MSI Gel Saline HP application.
CITE: F 462 - 483, Exhibit 9 to California Braley Deposition. DUPLICATE: p A75\460 - 17482; T 2363 - 2383. NOTE: See 00/00/73 - F 12 - 16; P 17491 - 17496; and Depo. of Bobby Purkait, MDL 926, p. 50-51, Exhibit 22 (07/09/93).

Document #118
05/06/70
RUPTURE
SHELL STRENGTH - THICKNESS

J.K. Boone, Dow Corning , handwritten note to F. Stark regarding inflatable mammary development assurance. Boone writes:

"The bags for the inflatable mammary prostheses are taken directly from the production of the standard seamless mammary. It is expected that gel filled bags are softened by the gel somewhat, giving an ultimately softer bag with somewhat higher elongation. Thickness of the bags varies with the size and width, but it is ordinarily between 0/010" and 0.020" with the average being about 0/017.

Several individual prostheses were subjected to severe testing (after filling and tube removal). They were slammed repeatedly against a smooth wall. Valves functioned well, bags can be broken under stress without the valves leaking.

To date, 153 of these devices have been submitted to quality assurance, and 18 of these have been rejected for a variety of reason. Leakage through the valve has not been a problem.

It is very difficult to project the eventual clinical failure rate for this device at this time. I would estimate failures less than 1% on devices successfully implanted, another failure rate should be expected for devices damaged during surgery. These will be immediately detectable as these devices are filled. This will cause professional irritation but little liability. Patients are being cautioned that these devices may break or leak at some later date.... The device now marketed (gel filled) has certainly not been complication free but to date it has not caused us severe liability problems. Over the long haul, I would guess that we might be sued about as often for hard, painful breasts as for 'shrinking' ones."

Document #119
06/01/70
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
MISCELLANEOUS - COMPLICATIONS
SILICA
TISSUE REACTION

Minutes of the Inflatable Mammary Meeting sent to Bennett, Boone, Bennett, Hobbs, McIntyre, Olson, Rathjen and Stark.

CITE: KMM 77733 - 77750, Exhibit to Bennett Deposition and Exhibit to
Isquith Deposition.

Document #120. (ALSO LISTED AS 121.)
06/16/70
TESTING
SHELL STRENGTH - THICKNESS

Boone, Dow Corning, memo to Hobbs and others regarding the "Physical Property Testing on Two Year Implant Specimens." The study was by Food and Drug Research Laboratories on silicone elastomers implanted intraperitoneally, intramuscularly and subcutaneously. Fifteen dogs were tested with silicone elastomer and seamless mammary constructions. The results showed "in almost all cases (that there has been some rise in durometer with attendant loss in elongation and increase in modulus of the materials."
CITE: T 1573 - 1577. (Document # 121 on the Trial Exhibit List states that this document does not have a Bates Number).

Document #122
07/08/70
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Olson letter to Michael Robbins, Pharmaceutical Division of The Dow Chemical Company in Indianapolis, regarding Robbin's recent request for information on the toxicity of dimethylpolysiloxane when injected intravenously into laboratory animals. A search of the toxicology files at Dow Chemical reveals that preliminary acute and subacute studies were conducted in 1956 on Dow Corning 200 Fluid, 350cs." He then summarizes the data where 2 of 4 rabbits died immediately after being injected with DC 200 fluid at .50 g/kg, 2 of 4 died at 1 g/kg dose and all 4 died at 2 g/kg dose.
CITE: FDA 27229 - 27230, Exhibit to K. Olson Deposition, and Exhibit to Hinman Deposition.

Document #123
09/23/70
MISCELLANEOUS
SHELL STRENGTH - THICKNESS
STERILIZATION/CONTAMINATION

Dow Corning Corporation Report entitled "Manufacture of Silastic Mammary Prosthesis." The purpose of this report is to provide a detailed description of the manufacturing processes involved in the production of Silastic Mammary Prostheses. The report gives a detailed description of the manufacturing facilities, product composition, processing materials, component specifications, manufacturing process and quality assurances. This report also includes product run sheets for the seamless mammary prosthesis and packaging component information and specifications.
CITE: KMM 223739 - 223806.

Document # 124
01/21/71
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Handwritten memo to Hunter from Bennett regarding "Trip Report -Europe, Jan. 6-20, 1971." Section 2, beginning on p.10, discusses a visit with Lepetit Pharmaceutical co. in Milano on January 14-15, 1971. Present at this meeting were Wm. Caldwell, Zeller - Director of Central R&D, Carati - Lepetit legal counsel, Levier and Bennett. Levier and Bennett also met with Lerner.
CITE: DCC 281011474 - 281011491 (Temporary Dow Corning Bates Numbers 5455 - 5472), Exhibit to Bennett Deposition, Exhibit to Hinman Deposition, Exhibit to Isquith Deposition, Exhibit to Julius Johnson Deposition, Exhibit to LeBeau Deposition, and Exhibit to LeVier Deposition.

Document #125
01/26/71

Wayne Koning, Dow Corning, memo to Forrest Stark regarding a returned implant by Dr. Bankof. Jan Varner reported that this was an "old" style implant and that he "was able to break through the envelope with minimal effort and perhaps there is some degradation of the envelope over a period of time."

Koning reports to Stark that "Jan appears to be loosing confidence in the stability of the envelopes physical properties over an extended period of time because of frequent comments that are being given recently by large volumes (sic) users that he calls on." Koning also states that, "The terms, friable, disintegration and degradation are being used frequently in some areas to describe the condition of the envelope of removed SILASTIC (R) mammary prostheses."
CITE: M 570119. DUPLICATE: KMM 335110

Document #126
03/09/71
COHESIVENESS - LIQUID COMPONENT OF GEL
RUPTURE
TISSUE REACTION

Morgan, Dow Corning, memo to Koning, regarding a complaint made by Dr. Condie concerning the composition of the silicone gel in a ruptured implant. The patient developed a reoccurring infection and staph infection four months post-op with fluid "oozing from the wound." The memo states "the prosthesis was practically empty of gel and what gel was there was extremely fluid and oozed out of the prosthesis and the surrounding tissue.... It appears to me that we have had a gel breakdown but I did not discuss this in any way with Dr. Condie."
CITE: KMM 423343 - 423344. DUPLICATE: KKA 152366 - 152367; CO 82 - 83. NOTE: Dow Corning was using V. Mueller as its sales agent.

Document #127
05/11/71
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Dr. Glenn Burt, Department of the Army, letter to Silas Braley, Dow Corning, reporting on an augmentation patient who "encountered a most traumatic experience. On the second postoperative day the patient developed a fever which during the next few days spiked tremendously - as high as 105 degrees - and the patient went progressively down hill so that we had to remove the prostheses on the twelfth post-operative day.... During this time she developed an erythematous rash, joint swellings, considerable weakness, and an enlarged liver, all of which made us feel this was a rejection type phenomenon."
CITE: M 240089, Exhibit 46 to Hinsch Deposition (used by Dow Corning), Exhibit to D. McGhan Deposition, Exhibit 21 to California Braley Deposition, and Exhibit 5 to Harris County Burchiel Deposition.

Document #128
06/14/71
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Dr. Condie writes to Wayne Koning, Dow Corning, regarding a patient with breast implants who developed and "allergic reaction in the skin over the right breast, or an infection in the skin of the right breast. There was slight itching associated with the condition. This was also associated with some swelling of the upper lip and it was felt that she might have angioneurotic edema, however, with antibiotic therapy the cellulitis cleared up. This was approximately 16 days after she was first seen for the condition." Six months later, the right breast again became red and swollen. Upon aspiration, silicone escaped from the needle's puncture wound, resulting in wide spread necrosis. The implant was removed and Dr. Condie noted that "it was extremely difficult to remove all of the silicone which was flowing and not gel like in consistency." Dr. Condie also states that the silicone in this case was "extremely watery and flowed very easily. I cannot help but feel in my own mind that there was something which caused chemical change in the silicone, making it liquid instead of a gel. The culture which was taken showed staph coagulasa positive."
CITE: M 570103 - 570104. DUPLICATE: KMM 98372 - 98373; M 240090 -240091.

Document #129
07/07/71
SHELL STRENGTH - THICKNESS

Manikian, Dow Corning, memo to Boone stating that he has accumulated data on the "long term" stability of the envelope. He refers to three lost of mammaries - 1 from June 1966, 1 from August 1967, and 1 from April 1971. "There are changes in the physical properties of the bag after filling. Contact with the gel seems to soften the bag and lessen its tensile strength.... (W)e neither have data on the properties of a bag immediately after filling nor have in storage a large enough number of units to perform a controlled study."
CITE: KMM 220303. DUPLICATE: KMM 223111 - 223114.

Document #130
12/13/71
STERILIZATION/CONTAMINATION

W. Koning memo to Bill Mantle, Dow Corning, which states "Bill, here is another hairy implant from Jan! Please comment. Too bad they didn't reject before unsealing the package."
CITE: KMM 423367.

Document #131
12/00/71
EMBOLISM
GEL MIGRATION
KNOWLEDGE OF LIQUID SILICONE DANGERS
MISCELLANEOUS - COMPLICATIONS

Publication by Blocksma entitled "Experience With Demethylpolysiloxane Fluid In Soft Tissue Augmentation." Plastic & Reconstructive Surgery, Vol. 48, No. 6, 564-567. The release of silicone fluid for general distribution could make every general surgeon think he has become a plastic surgeon overnight. Used improperly, silicone fluid has a serious potential for harm. Therefore the author is opposed to the release of this material to any but bona-fide plastic surgeons at this time.
CITE: DCC 204005370 - 204005374; Exhibit 71 to Braley Deposition, Exhibit to D. McGhan Deposition, Exhibit 45 to Hinsch Deposition (used by Dow Corning), and Exhibit 99 to Harris County Rathjen Deposition.

Document #132
00/00/72
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Article by Bennett, Gorzinski and LeBeau entitled "Structure-Activity Relationships of Oral Organosiloxanes on the Male Reproductive System," Toxicology And Applied Pharmacology, Vol. 21, 55-67 (1972). The abstract at the beginning of the article states that:

"A series of low molecular weight organosiloxanes depressed male reproductive function in the mouse, rat, and rabbit. The rabbit was the most sensitive, and the mouse was the least. Active compounds were found among phenylmethyl-substituted silanes, linear disiloxanes, and trisiloxanes; cyclic trisiloxanes and tetrasiloxanes. Cyclic siloxanes were the most active cyclic. Monophenylheptamethylcyclotetrasiloxane was quite active; however, the presence of an additional phenyl group enhanced activity providing the 2 phenyl groups had the correct sterile configuration, i.e., 2,6-cis-diphenylhexamethylcyclotetrasiloxane....

A spectrum of activity was noted in the male animal when active compounds were administered po for 3-21 days. Small doses sequentially decreased seminal fluid, seminal vesicle, prostate and testes weight, associated with decreased blood levels of testosterone. Large doses caused adrenal hyperplasia, hepatomegaly, decreased body weight, and decreased serum levels of cholesterol, phospholipids, and alkaline phosphatase."

CITE: DCC 281000743 - 281000755. WITNESS: Bennett (Authenticated in Bennett, Vol. II, p. 547-548). DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare.

Document #133
04/00/72
FRAUD/MISREPRESENTATION

Dow Corning advertisement: "The Silastic Mammary Prosthesis makes a world of difference." Over the past ten years "we have initiated 207 rigid quality control tests to assure the reliability of every prosthesis manufactured. We have continued to make significant design improvements. It is simply the most reliable answer to breast augmentation and restoration following subcutaneous mastectomy."

CITE: M 700010. DUPLICATE3: KKH 62691; KKH 62692; M 370064; M 370065; M370106; M 370123: M 700011

Document #134
04/07/72
GEL MIGRATION

"Dimethylpolysiloxane Fluid 14C (Dow Corning 260 Medical Fluid 14C) Distribution and Disposition In Rats Following Subcutaneous Injection," by LeBeau and Gorzinski of the Research Department of DC. A copy was sent to Ryan, Bennett, Braley, Hunter, Isquith, Frye, LeVier, Speier, Stark, Boley and others. DC 360 fluid was administered subcutaneously to rats to measure the distribution of the fluid in expired air, urine and feces at 8, 30, 60 and 90 days. The highest percentage (.94%) was detected at the original injection site <10% was detected in urine and feces. "There was a ubiquitous distribution of low concentrations of radioactivity in the tissues and organs (<.02%). However, lymphatic tissue near the injection site had a higher (ten-fold) concentration of radioactivity of all tissues and organs examined suggesting migration via lymphatic routes."

Rodents receiving massive subcutaneous doses of silicone fluid were examined histopathologically. Droplets of vacuoles were found throughout the reticuloendothelia systems including the regional lymph nodes and extending to the liver, spleen, kidneys and adrenals. Definitive proof of silicone fluid in the droplets was not demonstrated but the authors assumed it was silicone fluid.

CITE: KMM 260056 and KMM 270609 - 270623, Exhibit to Bennett Deposition (used by plaintiffs and Dow Corning), Exhibit to Isquith Deposition, Exhibit to K. Olson Deposition, and Exhibit 3 to Harris County Rathjen Deposition. NOTE: The exhibit list also lists Bates Numbers T 2765 -2780 but there are no documents in the binder with these numbers. DUPLICATE: DCC 205001829 - 205001841; KMM 173800 - 173816; DCC 204004553 - 204004580;

Document #135
04/24/-26/72
TESTING
FRAUD/MISREPRESENTATION

Article entitled, "Toxicological Studies, quality control, and efficacy of the Silastic mammary prosthesis" is published in the journal Medical Instrumentation. Authors are Gordon Robertson and Silas Braley of Dow Corning. The article cites and discusses the FDRL Report on "Two-Year Studies With Miniature Silastic Mammary Implants" (P 017460 - 017496). Robertson and Braley reprint the 6 month test results in Medical Instrumentation and claim that these are the results after 2 years of implantation.

CITE: F 12 - 26, Exhibit to Palensky Deposition, Exhibit 19 and 20 to California Braley Deposition, and Exhibit to LeVier Deposition. DUPLICATE: KMM 249816 - 249822, J 5223 - 5226.

Document #136
05/04/72
TISSUE REACTION
SHELL STRENGTH - THICKNESS
KNOWLEDGE OF GEL BLEED
GEL MIGRATION
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF LIQUID SILICONE DANGERS

Silas Braley, Dow Corning, letter to Dr. Douglas Lake expressing his reservations about the use of silicone to fill inflatable implants. He states:

(T)here is a very good reasons for this: the silicone fluid being of the same basic nature as the silicone polymer used to make the rubber will dissolve into the rubber and very seriously weaken and soften it... Another factor which must be taken into consideration if a silicone fluid is used to fill a silicone rubber bag, is that the outer surface of such a bag will become oily with the silicone fluid. This means that the fluid is now capable of being absorbed by the body and very extensive toxicological work would have to be done to prove that this is not deleterious to the tissues.... We rejected the silicone fluids for the above reasons and went immediately to silicone gel. (emphasis added).

CITE: KMM 141906 - 141907, Exhibit 32 to California Braley Deposition.

Document #137
07/14/72
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Dow Corning Research Report No. 4006 (formerly classified) entitled "A Toxicological Evaluation Of Trimethylsilanol (Me3Si(OH2) In The Rat." The authors postulated that two potential end products of the biological degradation of trimethyl en-blocked linear dimethylpolysiloxane polymers or cyclic dimethylpolysiloxane polymers might to Me3SiOH and Me2Si(OH)2. Other studies are currently underway at Dow Corning's Biomedical Research Department to determine the potential for degradation of dimethylpolysiloxan polymeric species. (p. 4)

The authors conclude that there were no significantly different dose-related values for body weight, food consumption, hematology or organ weight ratios for liver, kidneys, adrenals, heart or gonads. There did appear to be a modest dose-related significant elevation of blood glucose in the Me2Si(OH)2 treated rats. There may also be a slight depression of the triglyceride blood level at the low dose of Me3SiOH and total lipid is at the low level of normality for this group as well. (p. 13)

CITE: DCC 281001689 - 281001726 (Temporary Dow Corning Bates Number 3424 - 3461), Exhibit 49 to Bennett Deposition (used by Dow Corning), Exhibit to Frye Deposition, and Exhibit to Isquith Deposition.

Document #138
08/18/72
MISCELLANEOUS - COMPLICATIONS
SILICA
TESTING
TISSUE REACTION

Robert LeVier and Michael Jankowiak, Dow Corning, report on "The Effects of 20 CS DC-360 Fluid And Related Linear/Cyclic Dimethylpolysiloxanes Administered Orally And Dermally For Four Weeks To Male And Female Rats On Whole Body Oxygen Consumption, Serum Total Cholesterol, Organ Weights, And Silicon Distribution." There was increase in tissue thyroid weight; potential of accumulation increasing cholesterol; and slight increases in silicone levels for heart, serum, urine, liver and thyroid. In addition, the female rat appeared to accumulate more silicone than did the male rat.
CITE: DCD 154000169 - 154000188, Exhibit to Bennett Deposition. NOTE: The exhibit list identified this document as T20844 - 20863.

Document #139
10/17/72
COHESIVENESS - LIQUID COMPONENT OF GEL
RUPTURE
SHELL STRENGTH - THICKNESS

Dr. Gregory letter to Rathjen regarding an implant he ruptured unknowingly during surgery. Three months after implantation, the patient experienced redness on her breast and perforation of the skin with the implant protruding outside and "Gel dripping out of the hole." He says that this "may be a blessing in disguise, because perhaps we have all been trying to make too soft and too fragile an envelope. I do not believe that the old envelope would have perforated as easily as this one did with the mosquito hemostat. Perhaps the viscosity of the Gel may have to be reconsidered in view of this particular type complication."

CITE: KMM 54876 - 54877, Exhibit 9 to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition. DUPLICATE: B 949 - 950.

Document #140
11/16/72
ACKNOWDEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS COMPLICATIONS
TESTING
TISSUE REACTION

Dr. Bennett, Dow Corning, "Bioscience 1972 Status Repost." Bennett states that "The interaction of the Chemicals in the biological organism can be detrimental to the consumer. A chemical which has no overt direct action in its own right but potentiates the action of a second chemical taken into the organism simultaneously, forces us to consider each

produce in its use situation to make sure that this phenomenon is not a hazardous one if it exists." (p., 1) Also, biological research in all areas is being constrained because of economic considerations. "There is considerable interest in chemicals which affect viruses, cancer, population control, immuno-therapy, animal and plant hormones, aging, and genetic engineering." (p.2)

Bennett recounts the major projects of each of the segments of the Bioscience Research Department: Animal Sciences - there is a continuing Evaluation of 2,6-cis, working with KABI and others; Microbiology - a program has been developed based on the creation of antimicrobial activity on surfaces of many diverse types; Plant Sciences - they are exploring antitranspirant activity of polydimethylsiloxane fluid; and Metabolism of Organosilicon Compounds - Bennett believes this unit is the "keystone in the development of silicon chemicals in profitable biological applications as well as continuing to assure the Corporation of the safety of present products." (p. 4)

CITE: DCC 16001173 - 16001178, Exhibit to Bennett Deposition. WITNESS: Bennett (Authenticated in Bennett, Vol. III, p. 630-631). DISPOSITION; Admitted in Toole (II) v. Baxter Healthcare.

Document 141
00/00/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Antimicrobial Research" prepared by Dr. Isquith. The objective is to "investigate the effect of 'substrate-bonding' of organosilicon antimicrobial agents on their potency; spectrum of activity; reaction to their agents (i.e., protein, lipids, detergents; mode of action; biodegradability; and toxicity in comparison to similar non-silicon containing agents."

(DCC 16001104) Isquith notes that Weetall and co-workers published a series of articles on the use of alkoxysilanes to immobilize enzymes on inert surfaces, and that this technology is currently being developed as a processing aid in various industries. He states, "The bonded biologically active agent concept is further expected to greatly alter the immunological field...." (DCC 16001105) He notes a potential business opportunity for Dow Corning.

CITE: DCC 16001104 - 16001109.

Document #142
00/00/73
ACKNOWLEDGEMENT OF NEED FOR TESTING KNOWLEDGE OF SYSTEMIC DISEASE
SILICA

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Exploratory Virus and "Cell Biology" Prepared by Dr. Robert Lake. The objective is to "Examine the role of enjogenous Si, organosilicon modified viral antigens, and endogenously applied organosilicon compounds in modifying humoral and cellular-mediated immune response to animal viruses." (LAK 50) There are three approaches to viral diseases - immunological, host-resistance, and chemotherapy. Defining a role for silicon containing chemicals in the immunological or host-resistance approaches will require examination of the basic interaction of these chemicals with the lymphoid elements of the cellular immune system, i.e., lymphocytes, monocytes, and granulocytes.

When organopolysiloxanes are installed in the blood, lungs, peritoneum or GI tract of the body, they illicit a selective interactive with macrophages. Macrophages are the first to encounter and process viral antigens in the immune response and "virtually control the outcome of and recovery from virus infection." (LAK 50) The material is phagocytized by neutrophils and macrophages, redistributed to lymphoid tissue and a fibrous wall builds around the material. It is this interaction of macrophages that Dr. Lake would like to study because "the potential for organosilicones as modifiers of immunological phenomena has not been exploited." (LAD 52) He states, "Critical variables such as polymer type, size, and organofunctional groups on the time course of these cellular responses have never been reported." (LAK 50)

CITE: LAK 50 - 52, Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit 1 to Randonovich Deposition, Exhibit to Boley Deposition, Exhibit 4 to Lake Deposition, and Exhibit to LeVier Deposition, DUPLICATE: LAK 47 -49. WITNESS: Bennett (Authenticated in Isquith, Vol. II p. 423:15 -424:11). DEPOSITION; admitted in Toole (II) v. Baxter Healthcare.

Document #143
00/00/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DESEASE

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Organosilicone Polymer Particle Technology." The objective is to "Synthesize uniform particles of a number of organosilicon resin polymers" to create reactive drug sites on these particles. The particles could be given locally or systemically as direct drug deliver systems, i.e., the instillation of a local anesthetic bonded to an organosilicon resin in joint spaces, GI tract, etc. to relieve pain. They could also be diagnostic or therapeutic uses such as binding antigen and/or antibody or used in diagnostic immunological tests. (DCC 16001050)
CITE: DCC 16001050 - 16001055.

Document #144
00/00/73
TESTING
FRAUD, MISREPRESENTATION

Robertson and Braley, Dow Corning, author "Toxicological Studies, Quality Control, And Efficacy Of The Silastic Mammary Prosthesis," relying on the 1970 dog study. They use a chart to illustrate complications and claim that the findings are the results at the end of the two-year study, when the chart is actually the findings at six months.
CITE: T 3003 - 3006

Document #145
00/00/73
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION

A Dow Corning study examines the suitability of injectable silicone fluid for soft tissue augmentation. Four observed positive tumorigenic findings of fibroadenoma and fibrosarcoma are dismissed as tumore characteristically and typically seen spontaneously in rodents and not related to treatment with silicone fluid. Data reveals phagocytosis evidenced by the presence of macrophage histiocytes and basal giant cells, with absorption of silicone and deposition throughout the reticuloendothelial system.
CITE: KMM 48449 - 48498.

Document #146
03/12/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
GEL MIGRATION
SHELL DEGRADATION

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Biodegradation" prepared by Dr. Isquith of Dow Corning. The objective is "To determine the ability of microorganisms to biodegrade a polydimethylsiloxane (PDMS) structure and the subsequent microbial fate of its degradation products."
CITE: DCC 16000273 - 16000279

Document #147
03/19/73
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study from Bennett, Statt, LeBeau, Golzinski, E. Wiessbruger, J. Weissburger and Ulland regarding item 17, "Primate Absorption and Elimination Balance Studies Including Pulmonary, Urinary, Biliary and Fecal Excretion of T-butanol, Trimethylsilanol, Dimethylilanediol and Hexamethyldisiloxane," item 18, "Primate Absorption and Elimination Balance Studies Including Pulmonary, Urinary, Biliary and Fecal Excretion of Octamethyl-cyclotetrasiloxane and 2,6-cis-Diphenylhexamethylcyclotetrasiloxane," item 19 "Chronic Toxicity and Carcinogenicty of Industrial Chemicals and Pesticides."
CITE: DCC 281061215 - 281061216, Exhibit 56 to Bennett Deposition (used by Dow Corning).

Document #148
04/05/73
EMBOLISM
KNOWLEDGE OF LIQUID SILICONE DANGERS
STERILIZATION/CONTAMINATION

Report by S. Braley, Dow Corning, of telephone conversation with Mrs. Herman D. Jones of the Georgia Crime Lab regarding a death caused by a breast injection of silicones. Pathologist reports large amounts of silicone emboli in the brain and lungs. In the case of the breast tissue, the silicone was dripping out. Current testing equipment and procedures will accurately test for the carbon silicon bond but will not detect where the silicone came from, whether there were additives in the silicone or whether it was pure silicone. They will detect whether they were phenyl methyl silicones or all methyl.
CITE: KMM 305064 - 305065.

Document #149
05/02/73
SHELL STRENGTH - THICKNESS
RUPTURE

Gary Corbeill, Reliability Engineer for Dow Corning, analyzes a Silastic Round implant returned by Drs. Terino and Sengleman to Bill Mantle, who in turn sent them to Art Rathjen. Corbeill states that, "Due to their thin 'skin' these mammaries are delicate and will rupture when subjected to undue pressure." (emphasis added).
CITE: CR 160 - 161. NOTE: Bill Mantle is the sales representative for the Los Angeles area.

Document #150
05/22/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Exploratory Antigen Modification," prepared by Dr. Isquith of Dow Corning. It was later re-titled "Silicon-containing Antigens." The objective is "To determine the capability of organosiclicon-midified antigens to stimulate or reduce immunogenic response." Isquith suggests a direct modification of antigens by chemical attachment of low molecular weight organosilicon moieties" as an alternative to other antigens (such as peanut oil) which cause adverse health effects. (KMM 546449) He states that, "This project is aimed at examining the effect, if any, of silicon-modification on known antigens. The value will be in the immuno-therapeutic valve of the modified effects. An increase or decrease in antibody synthesis, caused by antigen modification, may be desirable." (KKM 546453)
CITE: KMM 546448 - 546453, Exhibit to Bennett Deposition, Exhibit to Blocksma Deposition (used by Dow Corning), Exhibit to Radonovich Deposition, Exhibit to Isquith Deposition, Exhibit to Tyler Deposition, Exhibit to Boley Deposition, Exhibit to LeVier Deposition, and Exhibit to Lake Deposition. This document also has the Bates Number KMM 491075A - 491080A on it. WITNESS: Bennett (Authenticated in Isquith, Vol. II, p. 355: 1-6 and 357: 13- 16). DEPOSITION: Not introduced in Toole (II) v Baxter Healthcare.