Implant Veterans of Toxic Exposure

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What the Dow Corning corporate documents had to say about disease in connection with breast implants.                     

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.  Dow Corning Trial Exhibit List Abstracts

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 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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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 #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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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. Dow Corning Trial Exhibit List Abstracts

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 to another 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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

Document #68
8/02/66
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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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...." (emphasis added).

CITE: I 661 - 702. DUPLICATE: KMM 115833 - 115873; (Referenced in KMM407480 - 407482). NOTE: See 12/31/87 entry in Master Timeline.   Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.   Dow Corning Trial Exhibit List Abstracts

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).  Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.    Dow Corning Trial Exhibit List Abstract

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.  Dow Corning Trial Exhibit List Abstracts

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. Dow Corning Trial Exhibit List Abstracts

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 month.

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). Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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.

Dow Corning Trial Exhibit List Abstracts

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." (emphasis added).

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.  Dow Corning Trial Exhibit List Exhibit

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." (emphasis added).

CITE: M 570103 - 570104. DUPLICATE: KMM 98372 - 98373; M 240090 -240091.  Dow Corning Trial Exhibit List Abstracts

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.

Dow Corning Trial Exhibit List Abstracts

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.  Dow Corning Trial Exhibit List Abstracts

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. Dow Corning Trial Exhibit List Abstracts

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. Dow Corning Trial Exhibit List Abstracts

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 #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.  Dow Corning Trial Exhibit List Abstracts

Document #153
06/00/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE 

Dow Corning Bioscience Research Laboratory "Research Project Description" entitled "Silicon Adjuvants." The objective is to "investigate the action of silicon compounds on the humoral and cellular immune response." (DCC 16001092) "Substances which are non-immunogenic or only slightly immunogenic can often be made strongly immunogenic by simultaneous administration with adjuvants." (Id.) Because of the drawbacks with presently known adjuvants, research will determine if the cellular or humoral response can be selectively enhanced through the use of organosilicon compounds.

CITE: DCC 16001092 - 16001093, Exhibit to Bennett Deposition (used by plaintiffs and as Exhibit 83 by Dow Corning), Exhibit to Boley Deposition, Exhibit to Isquith Deposition, and Exhibit to MDL LeVier Deposition.

WITNESS: Bennett (Authenticated in Boley, Vol. I p. 141-143 and 153: 19 - 154:12). DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare.  Dow Corning Trial Exhibit List Abstracts

Document #155
06/16/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning bioscience Research Laboratory "Research Project Description" entitled "Exploratory Hapten Modification." The objective is to "determine the antigenic (haptenic as well as conjugate) capability of organosilicones of various molecular weights and to explore their potential use as biological tracers." (KMM 546454) Among the organosilicon compounds to be examined for determination if they function as conjugates or complete immunogens are dimethylpolysiloxanes. Research in this area will most certainly advance our knowledge of the chemical reactions of organosilicone compounds to biological chemicals.... The development of specific antibody in response to organosilicon determinant groups would provide us with an exquisitely sensitive biological tracer for detecting distribution and storage of organosilicones in the body." (KMM 546455)

CITE: KMM 546454 - 546465, Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit to Boley Deposition, Exhibit to LeVier Deposition, and Exhibit to Lake Deposition. This document also has Bates Numbers KMM 491081A - 491083A on it. WITNESS: Bennett (Authenticated in Isquith, Vol. II, p. 378:21 - 379;16). DISPOSITION; Admitted in Toole (II) v. Baxter Healthcare. Dow Corning Trial Exhibit List Abstracts

Document #160
10/00/73
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING
TISSUE REACTION

Publication by Rowlett, Nichols, Bailey and Dion titled "Silicones -Can They Further Improve The Quality of Life?," Dow Corning News, Vol. 15, No. 4, Sept. - Oct. 1973. Includes a description of the Bioscience Facility, the History of Bioscience activity at Dow Corning. States that 2,6-cis can alter their behavior of the pituitary, the master gland that chemically controls the function of all the other glands in the body. Describes Bioscience research as opportunity-oriented or for developing profit making products.

CITE: DCC 282001118-282001149, Exhibit to Bennett Deposition, Exhibit to Petraitis Deposition, Exhibit to Tyler Deposition, Exhibit to Boley Deposition, and Exhibit 1 to Randonovich Deposition. DUPLICATE: LAK 1 - 11.  Dow Corning Trial/Exhibit List Abstracts

Document #164
01/23/74
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Boley and LeVeir memo regarding organosilicon immunopotentiators. Forty-eight silicon-containing compounds were examined in guinea pigs for their ability to enhance serum antibody levels. Nine of the compounds showing high enhancing activity were further evaluated in a rat model. Of the nine, four prolonged and enhanced serum antibody levels.

CITE" DCC 281061454 - 281061486 (Temporary Dow Corning Bates Numbers 16362 - 16377), Exhibit to Bennett Deposition, Exhibit to Lake Deposition, Exhibit to LeVier Deposition, and Exhibit to Isquith Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #168
06/28/74
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING

United States Patent No. 3,821,373 for "Organosilicon Compositions In Methods Of Treatment Involving Increasing The Dopamine Content Of The Brain" granted to Donald R. Bennett and Robert R. Levier of Dow Corning. The patent is for the method by which the dopamine content of the brain is increased by administering 2,6-cis. The purpose of this is to alleviate some of the symptoms caused by Parkinsonism, manganese poisoning, and similar diseases.

CITE: DCC 281001098 - 281001100, Exhibit 3 to Isquith Deposition, Exhibit 70 to Bennett Deposition (used by Dow Corning). and Exhibit to LeVier Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #174
10/02/74
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Dow Corning Bioscience Research Report No. 4319 by Boley and LeVier, Dow Corning, entitled "Immunological Enhancing Activity Of Organosilicon Compounds And Non-Functional Fluids." Forty-nine (49) silicon-containing compounds were examined in guinea pigs to screen for "potential adjuvant activity." Nine compounds showing "good antibody producing activity" were evaluated for their ability to enhance serum antibody levels. Four compounds including (Me2Si0)4 showed good adjuvant activity. Dow Corning plans future work to evaluate these four compounds for their ability to enhance the antibody response to viral, bacterial and soluble proteins antigens.

Organosilicon compounds can stimulate the immune response. No information is currently available about the mechanism of action of these compounds.

CITE: T 21287 - 21304, Exhibit to Dillon Deposition, Exhibit to Frye Deposition, Exhibit to Bennett Deposition, Exhibit 14 to Edwards Deposition, Exhibit to Isquith Deposition, Exhibit to Harris County Klykken Deposition, Exhibit to LeVier Deposition, Exhibit to Lynch Deposition, Exhibit to Lake Deposition, Exhibit to D. McGhan Deposition, Exhibit to Palensky Deposition, Exhibit to Weyenberg Deposition, Exhibit to Compton Deposition, Exhibit 3 to Harris County LeVier Deposition, Exhibit 18 to Zimmer Deposition, Exhibit to Boley Deposition, Exhibit 1 to Harris County Boley Deposition; Exhibit to Hudson Deposition, Exhibit 23 to Harris County Rich Deposition, Exhibit to Harris County Burda Deposition, Exhibit to Frisch Deposition (used by Dow Corning), Exhibit to Oppelt Deposition Exhibit to Peters Deposition, Exhibit 10 to California Braley Deposition; Exhibit 1 to Dallas Espinoza Deposition, Exhibit to Radonovich Deposition, and Exhibit to Harris County Tyler Deposition. DUPLICATE: This was originally listed as P 14028 - 14046 on the exhibit list; DCC 80061481 - 80061530: F 86 - 103; DCC 281001575 - 281001589. WITNESS; Bennett (Authenticated in Boley, Vol. I, p. 155:4-24).

DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare.  Dow Corning Trial Exhibit List Abstracts

Document #177
00/00/75
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING 

Abstract of Lake, Radonovich and Boley report entitled "Potentiation of Endotoxin Induced Interferon In Mice Treated With Octamethylcyclotetrasiloxane." D4 increases serum interferon levels in mice induced with bacterial endotoxin, apparently potentiating production of "early" interferon induced by endotoxin but not viral-induced "late" or "virus-type" interferon. Forty-eight hours after intraperitoneal inoculation, mice exhibit weight loss, decreased spleen/liver weight ratio, decreased in vivo carbon clearance and peritonial monocytosis.

CITE: LAK 65 - 66A, Exhibit to Bennett Deposition, Exhibit to Lake Deposition, Exhibit to LeVier Deposition, and Exhibit 1 to Radonovich Deposition. NOTE: See entry dated 10/30/75. DUPLICATE: DCC 281061469 - 281061470. WITNESS: Radonovich. DISPOSITION; Admitted in Toole (II) v. Baxter Healthcare.

Dow Corning Trial Exhibit List Abstracts

Document #179
01/22/75
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING 

Study by Lake, Radonovich and Boley with abstract titled "Potentiation of Endotoxin Induced Interferon in Mice Treated With Octamethylcyclotetrasiloxane." D4 has been found to increase serum interferon levels in mice induced with E. coli endotoxin. Because spleen cells but not peritoneal exudate cells from D4 treated mice continue to produce augmented amounts of endotoxin-induced IF upon removal and incubation in vitro, a direct interaction between IF producing lymphoreticular organs and D4 is being considered.

CITE: LAK 67, Exhibit to Radonovich Deposition, and Exhibit to Boley Deposition.

Document #184
01/31/75
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Patent Memorandum Number 4320 by Boley, Lake and LeVier entitled "Organosilicon Immunopotentiators" is received by Dow Corning's Patent Department on this date. The memorandum essentially outlines findings that various organosilicon fluids potentiate the formation of humoral antibody, modulate cell mediated immunity and promote the induction of interferon by stimulation of the immune system." The document also includes a memo dated 08/03/76 from J.I. Pulley to LeVier noting that this patent memorandum has been inactivated and "that Dow Corning would probably not reactivate work in this area in the near future." Another memo dated 07/15/76 from Pulley to LeVier notes that "Dow Corning is no longer actively involved in this (the use of silicone fluids as immunopotentiators)...."

Another document is a "Patent Memorandum" by Boley and LeVier with the suggested title of "Immunological Enhancing Activities of Organosilicon compounds and Non-Functional Fluids" which was renamed to "Organosilicon Immunopotentiators." Nine of 48 silicon-containing compounds showed a "strong immunological enhancing" effect. Boley and LeVier wanted to explore possible applications of these compounds including for potentiation of veterinarian vaccines and in the "production of high quality and expensive experimental antibodies."

Some of these compounds were tested for their ability to augment or potentiate endotoxin induction of IF. Dow Corning 200 fluid and D4 "show a significant potentiation of endotoxin induced IF." (DCC 281061466).

There is also a one page abstract of the Lake, Radonovich and Boley report on "Potentiation Of Endotoxin Induced Interferon In Mice Treated With Octamethylcyclotetrasiloxane." Interferon appears to be involved in the Immune response to bacterial, viral and protozoal infections. Substances able to modulate the interferon response may be useful in the control of many infectious diseases and cancer. This report describes the immunopotentiating activity of some structurally defined linear and cyclic polydimethylsiloxane fluids which have been found to mimic the potentiating effects of mineral oil adjuvants (Boley and Levier Dow Corning Report 4319, 1974).

CITE: DCC 281061451 - 281061468 (Temporary Dow Corning Bates Number 16359 - 16379), Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit to Lake Deposition, and Exhibit to LeVier Deposition.   Dow Corning Trial Exhibit List Abstracts

Document #185
02/03/75
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING 

Patent department memo to Boley, LeVier and Lake regarding organosilicon immunopotentiators patent memo assigned #4320.

CITE: DCC 281061471 (Temporary Dow Corning Bates Number 16379), Exhibit to Lake Deposition, and Exhibit to LeVier Deposition. Dow Corning Trial Exhibit List Abstracts

Document #198
06/30/75
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION 

Study sent to Dowell by Lince, Pruitt, Neagele, Kenaga, Moss, Hymas Goring, Bjork, Coulter, Johnson, Osborne, Getzendaner, Meulder, Seymour, Sheldon, Barrons, Hinman, Laskowski, Gray, Hunter, Hanson, Little, Kurihara, Hamaker, Meikle, Regoli, Magana, Dalman, Edumura, Geronimo, Turner, Ferguson, Simon, Scott, MacDougal, Shaver, Fears and Regan regarding the rapidity of German roach knock-down with fospirate formulated on dri-die.

Dow Chemical U.S.A. Ag-Organics Research in Walnut Creek, California report by F.H. Dowell on "Rapidity of German Roach Knock-Down With Fospirate Formulated On Dri-Die." The report was distributed to numerous departments within Dow Chemical including Ag-Org. Information Center (M. Lince), Ag-Org. R&D Planning (name illegible), U.S. Area R&D Dir. M.E. Pruitt, Ag-Organics Dept. Manager RD Naegele, Ag-Organics R&D Director R.E, Hefner, Ag-Org. Regist. D. McCollister and E. Kenaga, Ag-Org. Chemistry Dir. R.D. Moss, Ag-Org. An. Health Devel. T.A. Hymas, Plant Sci. R&D Dir. C.A.I. Goring, Ag-Org Areas Pestic. Coord. L.L. Coulter, Corp. Prod. Dept. R.B. Johnson, Ag-Org. Synthesis Res. Mgr. D.W. Osborne, Ag-Org. Residue/Metab. M.E. Getzendaner, Ag-Org. Formulations K.G. Seymour, Ag-Org. Prod. Bus. Mgr. H.W. Sheldon, Ag-Org. R&D Tech. Advisor K.C. Barrons, Chem. Biol. Res. C.W. Hinman, Ag-Org. Environ. Studies D.A. Laskowski, Prod. Plan. Team R&D Spec. H.E. Gray, Res. Mgr. Field R&D R.C. Hunter: persons in the Ag-Org. department at the Walnut Creek lab; and to people in international locations.  

The 2% fospirate + Dri-Die Formulation appears to combine flushing action, residual rapid knock-down and indefinite slow residual action, all highly desirable properties in a roach control formulation. Dri-Die (micronized silica gel) is widely used for cockroach control.

CITE: TDCH 345 - 356, Exhibit to Bennett Deposition, Exhibit to Ryan Deposition, and Exhibit to Hinman Deposition. Dow Corning Trial Exhibit List Abstracts

Document #206
10/30/75
COHESIVENESS - LIQUID COMPONENT OF GEL
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Dow Corning Bioscience Research Report No. 4509 by Lake and Radonovich entitled "Action of Polydimethylsiloxanes on the Reticuloendothelial System of Mice: Basic Cellular Interactions and Structure Activity." The abstract for this report states that:

"Because of their hydrophobic character, dimethylpolysiloxanes of various viscosities are known to distribute to the reticuloendothelial system (RES) in association with phagocytes. The site, magnitude, specificity and time course of murine RES response to high doses of various dimethylpolysiloxane fluids has been studied to characterize the basic cellular interaction and immunological consequences of dimethylsiloxane administration. Type I interferon production and clearance of colloidal carbon were used to assess RES function. Linear 3,4 and cyclic 4,5 dimethylpolysiloxanes when given parenterally to mice caused a transient response in lymphoreticular tissues with a maximum at 48 hours. This response was found to involve phagocytic cells (macrophages) such that augmented amounts of Type I endotoxin-induced interferon are made. Carbon clearance by the RES is also depressed with the same time course as this hyper-reactivity to interferon induction. Hexamethyldisiloxane and dimethysiloxanes greater than 5 siloxy units do not cause these changes, but do cause a characteristic eosinophilia at an intraperitoneal inoculation site.

A consistent hypothesis for this observed increase in early interferon production is that dimethylsiloxanes in the 305 size range are sub-lethally surface active in macrophages of the RES. Like lead acetate and mineral oil-surfactant mixtures, which are known to augment early interferon production, low molecular weight dimethylsiloxanes decrease the phagocytic capacity of macrophages. Because endotoxin is not cleared (phagocytosed) or detoxified, the viable but phagocytically impaired macrophages undergo a prolonged and more complete interaction with endotoxin. (OOT 42327)"

CITE: OOT 42325 - 42352, Exhibit 1 to Radonovich Deposition (abstract only), Exhibit 23 to Harris County Hayes Deposition, Exhibit to Harris County Tyler Deposition, Exhibit 11 to Zimmer Deposition, Exhibit to Lake Deposition, Exhibit to Isquith Deposition, and Exhibit 23 to Harris County Rich Deposition. DUPLICATE: DCC 281001636 - 281001662; DCC 281061445 - 281061450. WITNESS: Radonovich. DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare. Dow Corning Trial Exhibit List Abstracts

Document #247
07/15/76
KNOWLEDGE OF SYSTEMIC DISEASE

Pulley memo to LeVier regarding "Patent Memo 4240 - Insecticidal Activity of Silicone Oils and Emulsions." The subject patent is being placed in our inactive files in the Patent Department. Note: The referenced patent memo is not attached.

CITE: DCC 281041374 (Temporary Dow Corning Bates Number 16359 - 16379), Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit to Lake Deposition, Exhibit to LeVier Deposition. Dow Corning Trial Exhibit List Abstracts

Document #249
08/02/76
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Hobbs, Dow Corning, memo to Atwell, Bey, LeVier, Radzius, Ryan, Smith, Stark, Gamon, Lentz, Maneri, Tyler, Wehrly, and Weyenberg regarding "2,6-cis Toxicity." Hobbs states: 

"A six month chronic toxicity study conducted on 2,6-cis has demonstrated possible relationship between the appearance of mammary tumors in the (word is cut off) and the feeding of the chemical. This possibility may have implications which involve products other than 2,6-cis. There are three major questions we must answer concerning this possible effect:

1. Is the occurrence of mammary tumors an absolute response in the rat when fed 2,6-cis?

2. Do any of our products contain 2,6-cis?

3. Is the production of these tumors a result of the estrogenic activity of 2,6-cis or is it related to certain low molecular weight silicone compounds?

CITE: KMM 482556 - 482557, Exhibit to Tyler Deposition, Exhibit to Ryan Deposition. NOTE: The right hand side of the page is cut off.  Dow Corning Trial Exhibit List Abstracts

Document #250
08/03/76
KNOWLEDGE OF SYSTEMIC DISEASE

Pulley, Dow Corning, memo to LeVier concerning the inactivation of Patent Memorandum 4320. Because LeVier represents "that the project which supported the subject disclosure in on the shelf and that Dow Corning would probably not reactivate work in this area in the near future," the patent memo is inactivated, to be reactivated "whenever you consider it appropriate."

CITE; DCC 281061472, Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit to Lake Deposition, and Exhibit to LeVier Deposition. NOTE; Refer to entry dated 01/31/75. This was listed on Plaintiffs' Exhibit List in Carter as "No Bates Number."

Dow Corning Trial Exhibit List Abstracts

Document #252
08/23/76
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE
RUPTURE

Jim Rudy, President of Heyer-Schulte sends a "Dear Doctor" letter regarding "the possible and known problems and complications" of breast implants. It is noted that subtle processes of degradation should be expected to occur, and that the knowledge associated with long-term implantation is imperfect. If the implant is torn the gel will migrate and that is why Heyer-Schulte placed warnings in data sheets in May 1975. Doctors and patients should expect some patients to exhibit adverse response to silicone implants.

CITE: M 190413 - 190417, Exhibit 159 to Harris County Powell Deposition, Exhibit to Harris County LeVier Deposition, Exhibit to Nawash Deposition, and Exhibit 140 to Harris County Rathjen Deposition. DUPLICATE: GEG 004050 - 004054; KMM 262028 - 262032; BAX 36899 - 36903. WITNESS: Rudy Exhibit 34; Hyans Exhibit 24. DISPOSITION: Admitted in Toole (II) v. Baxter Healthcare. Dow Corning Trial Exhibit List Abstracts

Document #253
08/24/76
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
TESTING
TISSUE REACTION

Hobbs memo to Atwell, Bey, LeVier, Radzius, Ryan, A. Smith, F. Stark, A. Gamon, "C. Lentz, R. Maneri, L. Tyler, J. Wehrly and D. Weyenberg regarding "2,6-cis Toxicity Action Meeting - 8/23/76." The parties met on 8/2/76 and discussed and agreed to the following activities: all products having potential for 2,6-cis formation will be identified along with their known uses: existing data will be reviewed to determine estrogenic potency of various low molecular weight organosilicon compounds when compared to 2,6-cis and/or DES: all areas will be identified where 2,6-cis is a known process by-product.

CITE: DCC 281031680 - 281031681, Exhibit to Harris County Tyler Deposition, and Exhibit to LeVier Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #257
10/01/76
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
RUPTURE
STERILIZATION/CONTAMINATION
TISSUE REACTION

Donald Barker, M.D., presents a paper, "Reactions to Silicone Implants in the Guinea Pig," to the Scientific Session of the American Society of Plastic and Reconstructive Nurses.

CITE: GEG 4000 - 40006. NOTE: Paper was published in the Aesthetic Plastic Surgery in 1978, authored by Barker and Sherrill Lee Schultz, R.N.  Dow Corning Trial Exhibit List Abstracts

Document #265
01/04/77
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TISSUE REACTION

Patent No. 4,001,403 for a method for reducing the reproductive function of mammals by Bennett and McHard. A method for altering the reproductive function of mammals by administering a pharmacologically effective amount of certain fluoroalkyl-substituted organosilicon compounds. As a means of illustration, one can orally or parenterally administer from 1.00 mg. to 100 mg. per kilogram of body weight of an organosilicon compound thereby rendering the subject (either a male or female mammal) infertile.

CITE; DCC 281061 - 281061408, Exhibit 73 to Bennett Deposition (used by Dow Corning). Dow Corning Trial Exhibit List Abstracts

Document #268
02/10/77
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Will Larson, Dow Corning, memo to Art Rathjen, Becker, Bennett, Bey, Kelley and Lewis concerning an allergic reaction in a patient of Dr. Vanduyn. The patient was implanted with a Silastic Mammary Prosthesis, No Fixation Patch. One month following implantation, the patient contracted the flu. Shortly thereafter, the implant "broke through" the healed incision and the implants were removed. The augmentation was redone and, within days after the surgery, the implants again "broke through." Dr. Vanduyn suggested a possible allergic reaction and asked if there were any similar reports. Larson told him, "I was unaware of any allergic reaction to silicones" (emphasis added).

CITE: M 240368  Dow Corning Trial Exhibit List Abstracts

Document #285
09/07/77
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Dr. Ashley sends Art Rathjen, Dow Corning, a letter and medical records of a silicone injection patient who developed a mass the size of an orange and experienced reddening, hardness and itching at the injection sit on the thigh. The pathology report notes there was a "chronic inflammation reaction."

CITE: KMM 418633 - 418656, Exhibit to MDL Rathjen Deposition. DUPLICATE: I 6182 - 6190.  Dow Corning Trial Exhibit List Abstracts

Document #288
10/06/77
KNOWLEDGE OF SYSTEMIC DISEASE
STERILIZATION/CONTAMINATION
TISSUE REACTION

Hobbs memo to Atwell, Bey, Lentz, LeVier, Owen, Pearce, Ryan, A. Smith, F. Stark, J. Campbell, S. Guittard, L. Tyler and D. Weyenberg regarding "Minutes from 2,6-cis meeting of 9/20/77." Certain unvulcanized food grade elastomers contain 250-450 ppm 2,6-cis, 996 resin contains approximately 50 ppm, and DC 550 fluid using the new process contains 1-5 ppm. The verbal results of the genetic tests on 2,6-cis show positive results and "indicate aggressive action is necessary to evaluate the potential hazard of this impurity." Hobbs states that he has obtained technical and legal opinions from Joe Raddzius and Dr. Steve Carson.

CITE: DCC 281031108, Exhibit to Tyler Deposition, and Exhibit to LeVier Deposition. Dow Corning Trial Exhibit List Abstracts

Document #295
00/00/78
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Publication by LeVier, Chandler and Wendell titled "The Pharmacology of Silanes and Siloxanes, Biochemistry of Silicon and Related Problems." pages 473-514. The salient features of silicon chemistry that may be considered of interest to life scientists have been reviewed while the biochemistry of silicon compounds has received only brief comment because this subject remains largely unexplored. Indeed, so little is known that we continue to categorize structures only on the basis of intended use with some consideration for bioavailability and a few emerging trends relating activity to structure and reactivity. This approach at least allows a clear division of though between popular silicones known for their lack of bioactivity and the less well known reactive silicon compounds.

CITE: DCC 281061312 - 281061353; Exhibit 64 to Bennett Deposition (used by Dow Corning). Dow Corning Trial Exhibit List Abstracts

Document #300
03/16/78
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Bob LeVier, Dow Corning, memo to Bey and Nelson (both are in the Marketing Department) proposing development of the implantable gel implant. He writes, "The 180-day rabbit gel implantation study led to two conclusions based on the data:

l. The evidence for progressive subdivisions of gel is sufficient to warrant the conclusion that a hypothesis favoring efficacy in mammary augmentation and/or mammary reconstruction cannot be supported without further experimentation.

2. The evidence for the presence of small isolates of gel surrounded by potentially phagocytic cells is sufficient to raise a theoretical question concerning dissemination of gel or its components.

 LeVier states that animal studies are needed on these issues and on questions relating to gel subdivision "by connective tissue and gel-associated systemic toxicity," He has designed a study which will provide the "minimally required information ... (in) the shortest practical time course for completion and at as low a cost as possible." (emphasis added).

 CITE: F 744 - 746. DUPLICATE: M 3320004 - 320005. Dow Corning Trial Exhibit List Abstracts

Document #308
00/19/79
KNOWLEDGE OF SYSTEMIC DISEASE
GEL MIGRATION
RUPTURE

Handwritten letter advising that the gel represents a potential rupture or immunogenic problem and a mild inflammatory problem which is probably beneficial since this will stimulate encapsulation of the gel and help minimize gel migration. Gel will probably eventually be found in the regional lymph nodes. (emphasis added).

CITE: M 460274. Dow Corning Trial Exhibit List Abstracts

Document #313
07/03/79
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Spielvogel, Robinson and Hanneman titled "Metabolism of Cis and Trans 2,6 Diphenylhexamethylcyclotetrasiloxane In The Rhesus Monkey, Rat and Man," by Speilvogel, R.J. Robinson and Hanneman. A copy was sent to John Ryan, Bey, Frye, Hobbs, C. Lentz, Boley, Nelson, Rylee, Stark, Tyler, Weyenberg and others.

CITE: DCC 281002046 - 281002085 (Temporary Dow Corning Bates Number 3781-3820), Exhibit 6 to Isquith Deposition. Dow Corning Trial Exhibit List Abstracts

Document #319
01/22/80
KNOWLEDGE OF SYSTEMIC DISEASE

Joseph Connelly, M.D., writes to Dow Corning Wright about a patient whose Silastic implant ruptured when she was involved in car accident. The implants were removed shortly thereafter because the patient experienced draining fluid from the implant through the skin. The patient's family doctor performed tests "which he says are suggestive of chronic lupus erythematosus." He wants to know if Dow Corning has any information whether the silicone implants can cause lupus. (emphasis added).

CITE: CM 1133 -1134. He writes a second letter on 04/01/80 because Dow Corning did not respond to the first letter. For Dow Corning's response, see 04/23/l80 entry.  Dow Corning Trial Exhibit List Abstracts

Document #322
04/23/80
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning responds to Joseph Connelly, M.D., concerning his inquiry about a patient who developed lupus erythematosus following a rupture of a Silastic mammary implant. William Boley, senior Group Leader for the Health Care Group Research, responds:

"Dow Corning has performed extensive safety testing, in animals, on the silicone materials from which SILASTIC breast implants are made. I have also reviewed our product complaint files. Your inquiry appears to be the first Dow Corning has received asking whether a silicone breast implant could be a causative agent for chronic lupus erythematosus.

The data Dow Corning has suggest that it would be highly improbable that your patient's symptom of chronic lupus erythematosus could be attributed to the silicone breast implants."

CITE: CM 1135. NOTE: See 01/22/80 entry. Dow Corning Trial Exhibit List Abstracts

Document #331
12/10/80
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

"Metabolism of Octamethylcyclotetrasioxane in the Monkey, Report No. 5265," by Spielvogel and Robinson. A copy was sent to Boley, Hobbs, C. Lentz, LeVier, Stark, Frye, Ryan, Speier, Bey and others. D4 was administered orally to two monkeys and the excretions (urine and feces) were collected and examined. Gas chromatography-mass spectrometry revealed the presence of three metabolites: dimethylsilanediol, tetramethy1-1,3-disiloxane diol and hexamethyl-1c5-trisiloxane diol. The authors reasoned that D4 might undergo metabolic transformation to either an alkyl hydroxylated and/or conjugated species or silanol functional species that would likely be soluble in moderately polar solvents." (KP 30523). 

D4 appears to be well absorbed from the gastro-intestinal tract and broadly distributed throughout the body. The primary route of excretion is urine. "The bio-transformation of D4 is similar to that 2,6-cis and 2,6-trans-diphenylhexamethyltetrasiloxane and diphenysilanediol. All of the compounds appear to be readily hydroxylated and as a result are converted from highly lipophilic compounds to highly polar, easily excretable metabolites." (KP 30626). Also, "The metabolic fate of D4 closely parallels the metabolic fate of 2, 6-cis and 2, 6 - transdiphenylhexamethylcyclotetrasiloxane. All of the cyclic siloxane compounds examined to date are metabolized to a series of low molecular weight polar compounds that are predominantly excreted via the kidneys."

CITE: T 8796 - 8813, Exhibit to Harris County Ruhr Deposition, Exhibit to Bennett Deposition, Exhibit to Isquith Deposition, Exhibit to LeVier Deposition, Exhibit 4 to Stark Deposition, Exhibit to Compton Deposition, Exhibit to Ryan Deposition, Exhibit to Isquith Deposition, and Exhibit 31 to Zimmer Deposition. DUPLICATE: KKM 22739 - 227560 Dow Corning Trial Exhibit List Abstracts

Document #332
02/09/81
KNOWLEDGE OF SYSTEMIC DISEASE
GEL MIGRATION

Boley, Dow Corning, memo to Frisch, LeVier, Spielvogel, Cooper, Rylee, and Wessel regarding "Baboon Study To Evaluate the Fate of Silicone Wear Particles." Boley notes that:

"Silicone particles have been found in the axillary lymph nodes of patients with Silastic finger joints. These particles have been detected as a consequence of biopsy of nodes that have become painful and enlarged.... Of concern to the surgeon is whether these particles will continue to migrate beyond the regional nodes into the thoracic or abdominal cavities. Since concerns about malignancies requires that any chronic swelling of lymph nodes be biopsied or excised, wear particles could create the need for a surgeon to breach the body cavities.

CITE: KMM 328166 - 328167. DUPLICATE: KMM319434 - 319435. Dow Corning Trial Exhibit List Abstracts

Document #341
09/16/81
TISSUE REACTION
RUPTURE
KNOWLEDGE OF SYSTEMIC DISEASE

Dr. Vinnik's operative report to Dow Corning notes a patient who experienced a rupture and found an "irregular nodular mass" in her right breast which "became increasingly fibrotic and dense, raising some concern about malignancy. At surgery, the right breast was found to be totally disrupted with the implant shell incorporated within the gel mass. Contiguous with the gel mass and separately isolated by capsule, was a roughly 4x6 cm irregular nodular mass which upon excision was an obvious siliconoma." The attached pathology report notes that, "The process ranges from a fibrous rather acellular one through concentrations of lymphocytes and plasma cells to small foreign body type giant cells tending to form granulomas. One section demonstrates an acute necrotizing inflammatory cell reaction."

CITE: F 687 - 689 Dow Corning Trial Exhibit List Abstracts

Document #352
05/10/82
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

J. Cooper, Dow Corning, memo stating that the Two-Year Implant Study of Q7-2167 and Q7-2168 was flawed and useless. Cooper states that, "Prior to completion of the study and interpretation of the results IBT (Industrial Bio-Test Laboratories) was cited by the FDA for poor clinical/laboratory practices including loss of records and falsification of data. The corporation was subsequently dissolved." In addition, "the data were considered highly suspect because of abnormally high disease rates among all of the test animal groups -- including the saline injected and untouched groups.... We have since had opinions from several external pathologists and veterinarians that the colony was disease ridden and the entire exercise was badly flawed and useless. We have concluded this study has resulted in no usable information and that no conclusions can be drawn from it. We are now back at the same point we were at in 1975 except that we have expended $200M in the study and its subsequent evaluation/condemnation." (emphasis added).

CITE: F 814 - 815. DUPLICATE: m 170070 - 170071: M 430209 - 430210; KMM 361951 - 361952; KMM 339375 - 339378. NOTE: Dow Corning has no long-term studies and, even though they admit that "we still need the two year study...," Dow Corning does not begin another such study until 1988.  Dow Corning Trial Exhibit List Abstracts

Document #353
05/14/82
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Dr. Robert Parsons, Professor of Surgery at the University of Chicago, writes a letter to Gene Jakubczak at Dow Corning informing them of their research on implanted silicone prostheses. "our data suggest strongly that the fibrosis and capsular contracture seen clinically maybe (sic) an immunologically mediated phenomenon." (emphasis added). Dr. Parsons states that macrophages aggregate and adhere to the surface and actively erode the silicone envelope after implantation: macrophages ingest and process silicone; macrophag-lymphocyte communication occurs by intracellular bridging in the lymph nodes and have identified silicone containing microvacuoles in both the macrophages and lymphocyte ends of the bridges; and significant inhibition of macrophage migration by silicone sensitized lymphocytes in vitro has been shown. Dr. Parsons, Dr. Heggers and their research assistant, Nir Kossovsky, suggest that their work may enable them to develop a method of screening patients for "hypersensitivity to silicone" before they are implanted.

The research team found that the body's reaction to silicone created giant cells called macrophages that erode the silicone envelope and can migrate to the lymph nodes. Dr. Parsons believes that the body's immune reaction could be causing such problems as capsular contracture. Requests for finding from Dow Corning for further research to better understand this immune response were denied by the company.

CITE: F 748 - 749. DUPLICATE: FDA 19612 - 19613: KMM 447084 - 447085; Staff Report prepared by the Human Resources and Intergovernmental Subcommittee of the Committee on Government Operations, December, 1992, p. 15.  Dow Corning Trial Exhibit List Abstracts

Document #355
10/19/82
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Eldon Frisch, Dow Corning, responds to Richard Swett, M.D., concerning an allergy-type reaction to Silastic brand implants made from medical grade silicone. Frisch states:

"Clinically, the implants have been used in several million patients with very few reports of suspected inflammatory or allergic reactions. In the past, with one recent exception, when the reactions were evaluated by patch testing, by subdermal implantation of a small specimen, or by cell culture studies of the implant the reactions have universally been negative."

Frisch notes another report of a potential allergic reaction to silicone reported by George Francis, M.D. (emphasis added).

CITE: M 480031 - 480032.  Dow Corning Trial Exhibit List Abstracts

Document #368
01/26/83
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE
GEL MIGRATION
RUPTURE
TESTING
CONCEALING FROM FDA

Dr. Nirmal Mishra, staff toxicologist at the FDA, presents the FDA's reasons for this recommendation which include: gel migration, granulomatous foreign body reaction, loading of the reticuloendothelium system, unknown subsequent disposition in the body with little epidemiologic or experimental data on effects.

CITE KMM 120705 - 120729, Exhibit 3 to Harris County Rathjen Deposition. DUPLICATE; M 100083 - 100143. Dow Corning Trial Exhibit List Abstracts

Document #369
02/02/83
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE

Stark, Dow Corning, memo to Marlar, Rathjen, Steinberg, Jakubczak, Weyenberg, Lentz and Hobbs reporting that "the number and type of abnormalities noted with the 360 fluid studies in rabbits, i.e., classic cyclops condition of the eyes, clubbing of extremities, ankles bent in the wrong direction, were all indications of potential birth defects related to silicones: and the "this issue is of paramount importance. It has relevancy to the safety of all silicone applications and must be resolved ASAP.: (emphasis added). 

CITE: DCC 17042386 - 17042387, Exhibit to California Lentz Deposition, Exhibit 93 to Bennett Deposition, and Exhibit to MDL Rathjen Deposition. DUPLICATE: KKA 22785 - 22786.  Dow Corning Trial Exhibit List Abstracts

Document #372
04/01/83
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory patient no. 29 follow-up. The patient developed rheumatoid arthritis in the back and shoulders and has an over active thyroid.

CITE: B 1453 - 1454, Exhibit 14 to Harris County Rathjen Deposition, Exhibit to MKL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #376
07/20/83
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

C. Lentz, Dow Corning, memo to D. Weyenberg discussing staffing needs to conduct toxicological studies. He writes, "The work we do has a wide range of urgency connected with it. On one end of the range is the work that must be done now and on the other end is work which needs to be done some time but can be put off for now ...until it reaches the 'must be done now' stage." Lentze states that Dow Corning's current mode is that the toxicology department is understaffed or "inadequately' staffed, that they are "borrowing" pathology and veterinary skills from Dow Chemical and that Dow Corning has "no resources available to do long term studies or fundamental information type studies." Lentz urges Dow Corning to immediately hire two people to meet Dow Corning's "here and now obligations." A long term (2 year) state of the art study on the health effects, including carcinogenic potential of implanted silicone gel "must be done. Dow Corning no longer has the option of not doing or delaying the study.'

Lentz adds, "Commencement of a gel implant study is overdue and at this time we would not be able to convincingly demonstrate due diligence in pursuing knowledge."

One of the recipients of the memo, Forrest Stark, writes a handwritten note back to Lentz at the top of M 420069: "Bringing appropriate professionals in house has my wholehearted support. I still think that a reorganized TOX within HES could give us efficiencies." (emphasis added).

CITE: M 420068 - 420072, Exhibit to Harris County Boley Deposition, Exhibit 7 to Zimmer Deposition, Exhibit to Rylan Deposition, and Exhibit 19 to Harris County Zahalsky Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #377
08/09/83
ACKNOWLEGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION 

Memo to Rathjen from Isquith regarding Immunological Research Proposal, "It has long concerned me that our knowledge in this area is virtually nil and should not be. ... Knowledge from such a study ... could be a tremendous asset in better understanding tissue reaction to silicone implants."

CITE: KMM 205513 , Exhibit to Isquith Deposition and Exhibit 65 to MDL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #388
02/16/84
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Holmes, Dow Corning, memo to Rathjen regarding "S.H. Miller Study Protocol." Holmes states: "It seems almost inconceivable that we do not know more about the human immunological response to silicone at this point...." He states that the study is "certainly needed" and that Dow Corning should support it.

CITE: KMM 205503, Exhibit to MDL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #396
5/09/84
KNOWLEDGE OF SYSTEMIC DISEASE

Eldon Frisch, Dow Corning, memo to Bill Boley, Marcia Marsh, and Jim Wessel concerning Baxter Travenol's presentation at the biomaterials Meeting. The poster presentation demonstrated a cell culture method Baxter developed for assessment of immunotoxicity. Frisch states that Baxter "tested a number of materials, including silicones, and have found that many, if not most, plastics and elastomers elicit an immunotoxicity reaction. ... This may be of interest in the alleged case of human adjuvant disease." (emphasis added).

CITE: KMM 37828.  Dow Corning Trial Exhibit List Abstracts

Document #397
05/21/84
KNOWLEDGE OF SYSTEMIC DISEASE

Frisch, Dow Corning, letter to Dr. John Madden (cc to Boley) regarding a female hydrocephalic patient described in an attached abstract entitled "Evidence For Immune Response to Silastic Implants" by Michael R. Wasserman. The described patient experienced an alleged immune response to silicone elastomer.

CITE: DCC 10005769 - 10005770.  Dow Corning Trial Exhibit List Abstracts

Document #398
06/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up for patient no. 8. She developed arthritis in 1978, 6 years post-implantation.

CITE: B 1084 - 1085, Exhibit 11 to Harris County Rathjen Deposition, Exhibit to MDL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #399
07/09/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 48. Five years post-implantation she was diagnosed with idiopathic thrombocytopenia purpura.

CITE: B 727 - 750, Texas Exhibit No. 8, Exhibit to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #400
07/09/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 26. The patient developed arthritis in her fingers.

CITE: B 1401 - 1403, Exhibit 12B to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #401
07/09/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 47. The patient developed urinary bladder papiloma and a palpable node in the left axilla.

CITE: BL 676 - 709, Exhibit 17B to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #402
07/09/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 36. The patient developed rheumatoid arthritis in the upper extremities.

CITE: B 1584 - 1586, Exhibit 16 to Harris County Rathjen Deposition, and Exhibit To MDL Rathjen Deposition. DUPLICATE: DCD 173003868 - 173003869.  Dow Corning Trial Exhibit List Abstracts

Document #403
07/09/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 31. The patient developed discoid lupus in 1982.

CITE: B 1516 - 1517, Exhibit 15 to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #404
07/10/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Gregory follow-up of patient no. 50. The patient had minor arthritic changes in her hands.

CITE: B 804 - 805, Exhibit 18 to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition.  Dow Corning Trial Exhibit List Abstracts

Document # 407
08/27/84
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Operative report of a Gregory patient indicates a "tingling numbness which radiates up and down both legs. The point of onset varies each time; it may start in the groin, thigh or calf region but always involves both legs" She was diagnosed with aortofemoral stenosis.

CITE: B 1017 - 1019, Exhibit 10 to Harris County Rathjen Deposition, and Exhibit to MDL Rathjen Deposition. Dow Corning Trial Exhibit List Abstracts

Document #409
10/22/84
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Devries and Siddiqui, Dow Corning, report the results of the "Acute Oral Toxicity Study of Diphenylmethylsilanol In "Rats, "TX-84-0110-03. Signs of toxicity exhibited by rats include lethargy, tremors, slight ataxia and coma which terminated in death. The authors conclude that diphenylmethylsilanol is "slightly toxic" when ingested on an acute basis targeting the central nervous system.

CITE: T 29120 - 29165. DUPLICATE: CGS 1321 - 1322. NOTE: Refers to complaint CGS 1306 -1319. Dow Corning Trial Exhibit List Abstracts

Document 410
12/07/84
KNOWLEDGE OF SYSTEMIC DISEASE TISSUE REACTION 

Veresh, Dow Corning, report on the "Ninety-Day Implant Study of Dow Corning Q7-2218 Silicone Gel System." The pathologist noticed the presence of "a mild to moderate eosinophil infiltrate in the intramuscular and subcutaneous Q7-2218 implant sites in Rabbit #1564 at 30 days, and a trace eosinophil infiltrate at an intramuscular Q7-22l8 site in Rabbit #1570 at 90 days. Dr. Geil noted that the presence of eosinophil in a tissue response is considered indicative of an allergic response."

CITE: T 39610 - 39704. Dow Corning Trial Exhibit List Abstracts

Document #411
01/02/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Frye memo to C. Lentz regarding "1984 accomplishments." There is inconclusive daphnia data/D4 data. Frye also notes the "concerted year-end efforts to respond to the ITC recommendations for further testing of D4 for environmental fate and ecological impact. We might also include our efforts to head off publication of VanDerPost's silanol nonsense in a highly respected journal. It should at least qualify as 'fire prevention' effort where I would also classify our correspondence relating to Shin Etsu Hondotai's allegations of cyclosiloxane insecticidal (sic) properties and the Hutzinger et al manuscript alleging absorption and bio-transformation of a series of cyclic and linear oligomeric methylsiloxanes. Our Kyoto presentation was also an attempt to prevent silicones in aquatic sediments from being improperly categorized as ecologically threatening materials."

CITE: FRY 364 - 366, Exhibit 2 to Ryan Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #414
02/19/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Boley, Malczewski and Cooper of Dow Corning Health Care Group Research submit a Project Proposal titled "Investigation of the Effects of Silicone Fluids, Gels and Particles on the Immune System." Proposed is an immunotoxicology program involving "a series of animal tests and in vitro tests designed to assess the risk of adverse immunological sequela associated with the presence of silicone materials in the human." The authors note that silicone materials are causally linked to three different immunology-related disease states. First, a direct immunological sensitizations to implanted silicone material involving an immediate systemic response which is not correctable by explantation. Finally, the presence of silicone material in the lymphatic system may suppress the immune response to pathogenic organisms and tumor cells. Animal studies suggest that silicone materials modify the immune system both by eliciting a specific immune response and by nonspecifically enhancing or suppressing the immune system. Further, many recent clinical reports in the medical literature suggest that silicone materials elicit or modify the immune system. More sensitive testing methods by some researchers finding an immune response to silicone materials may explain conflicting reports by others who do not. Accordingly, proposed is a comprehensive screen of the immunotoxicity potential of silicone fluids, gels and particles. More than five series of sensitive in vitro tests will access nonspecific suppressing or enhancement of individual immune cell populations, as well as evaluate cell-mediated and antibody-mediated immune response to specific antigenic stimulation. Test will also evaluate the ability of animals to resist proliferation of pathogenic bacteria and tumor cells. Different species of animals will be used in the implantation studies to account for interspecies variations. Expected benefits from this testing include:

1. An assessment of the real risk potential for an immunological response to silicones.

2. An awareness of immunological problems that may erupt so that they can be engineered around if possible.

3. Five or six publications in literature to defuse the current wave of negativism toward silicones.

4. Possible ability to evaluate suspected human silicone sensitivity cases.

5. Data available for defense in lawsuits. NOTE: handwritten entry states "or prove guilty."

The authors estimate a recourse requirement of "6 effort years...expended over a 3 year period," and that "Health Care Group Research currently has adequate people skills and resources to conduct this work.

CITE: KMM 386643 - 386659, Exhibit to LeVier Deposition, Exhibit 21 to Harris County Hayes Deposition, Exhibit to Boley Deposition, Exhibit 12 to Popoff Deposition, and Exhibit to Isquith Deposition. Dow Corning Trial Exhibit List Abstracts

Document #415
03/07/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

B. Boley, Dow Corning, responds to A. Isquith's memo of 01/29/85 on "Genetic Toxicology Screen of Dow Corning Q7-2159A Gel." Boley states, "There is currently no valid carcinogenic test data on the silicone mammary gel Q7-2159A. I recognize that short term in vivo and in vitro mutagenicity tests are no substitute for a 2-year animal carcinogen study.... I feel the Health Care Business has an obligation to do what it can to assess the carcinogenic potential of this material.... Without this testing, I think we have excessive personal and corporate liability exposure." (emphasis added".

Boley authorizes tests such as the Ames Test, InVitro Forward Mutation Test, In Vitro Chromosome Aberration Test, and In Vitro Transformation Assay Test. According to Isquith's memo of 01/29/85, this is the "minimal testing" that would meet the FDA guidelines.

CITE" M 170039, Exhibit to Harris Country LeVier Deposition, Exhibit to Peters Deposition, Exhibit to Boley Deposition, Exhibit to Isquith Deposition, and Exhibit 20 to Harris County Zahalsky Deposition.  DUPLICATE: F 851; M 580051; DCC 17016611 - 17016613. NOTE: see 01/29/85 entry. Dow Corning Trial Exhibit List Abstracts
PENDLETONPSC Attorney Work Product/Privileged & Confidential

Document #418
04/10/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

R. Steele, Dow Corning, memo to G. Hignite regarding subjects discussed at a Health Care Business Board Meeting, Steele notes that the mission of the Health Care Business Board is on "internal profitability issues." One subject dealt with a presentation made by Bill Boley to the Executive Committee about a research study of the effects of silicone on the immune system. "The benefits of such a program would be to test for the real potential of immunological response to silicones.... Hopefully, we can diffuse any negativism that might exist toward silicone through publication of this data. This study would also give us the basis for an ability to potentially evaluate the sensitivity of individuals to silicone materials. Finally, the data would be available for defense in litigation proceedings."

CITE: F 842 - 846.  Dow Corning Trial Exhibit List Abstracts

Document #419
04/11/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Boley, Dow Corning, Memo to Hobbs, Lentz and Cooper regarding "HCB" Research Immunotoxicology Program." Boley states that the Health Care Business has approved research on immunotoxicology. Handwritten notes indicate that Al Munson, University of Virginia, is involved.

CITE: KMM 386642, Exhibit to LeVier Deposition, Exhibit to Boley Deposition, Exhibit 5 to Harris County Burchiel Deposition, and Exhibit to Isquith Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #424
07/30/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Boley, Dow Corning, memo to Cooper, Lentz, Rylee, Weyenberg, Yerrick, DeVries, Hobbs, and Siddiqui regarding "Summary of Meeting with IIT Research Institute to Discuss Immunotoxicology Testing of Silicone Materials." He identifies seven issues which Dow Corning must decide including "The major business issue of whether Dow Corning should commit to immunotoxicology testing of silicone materials." (underlined portion -emphasis in original). IIT Research Institute proposes to research adjuvant disease, immune sensitization, and immune suppression. Boley is "convinced that immunological testing of at least some silicone materials used for medical applications is appropriate." (emphasis added).

CITE: KMM 386490 - 386491.  Dow Corning Trial Exhibit List Abstracts

Document #425
08/08/85
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Dow Corning Study titled "Thirty-Day Implant Study of Dow Corning Q7-2218 Silicone Gel System" by Bejarano. He states:

Mild encapsulation of the gel by fibrous tissue was evident in nine of the ten test animals by unaided visual observation. Fibrous tissue encapsulation of the U.S.P. polyethylene control sites was not evident.

Microscopic evaluation of tissue sections of the intramuscular implant sites revealed a greater cellular response to the Q7-2218 gel than to the U.S.P. polyethylene control. In addition, increased numbers of eosinophiles were evident at the Q7-2218 gel implant site.

The presence of eosinophiles at the Q7 2218 gel implant site suggests the possibility of immunological sensitization to a component of the gel formulation. Additional studies are required to either substantiate or disprove the possible sensitization potential of this silicone gel.

CITE: T 31514 - 31571, Exhibit to Boley Deposition and Exhibit to Isquith Deposition. DUPLICATE: KKH 40082 - 40139.

 Document #430
10/10/85
GEL MIGRATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

Study titled "Characterization of C-U Silicone Elastomer Shells." The use of plastic embedding significantly enhances our ability to resolve the presence of silicone gel as well as those cells involved in the response. Plastic embedding provides retention of the interface between the fibrous capsule and the foreign body. The silicone gel is removed from the immediate locality and taken to the periphery of the capsule where one can only assume it is then transferred to the reticuloendothelial system as observed with similar materials used in other clinical situations A significant difference in degree of cellularity, number of lymphocytes and cells at the interface is noted when gel implants are compared to the extracted implants. It is my impression that the use of silicone gel prostheses represents a significant risk to the patient. The literature suggests that individuals can develop an allergic and immunologic reaction to silicone gel and oil. It would behoove us to develop in an expeditious fashion a non-permeable silicone shell with subsequent replacement of the gel with another polymer system.

CITE: CUI 300317 - 300414, Exhibit 11 to D. McGhan Deposition, Exhibit to Oppelt MDL and Harris County Depositions, Exhibit 7 to Harris County Pool Deposition, and Exhibit to MDL Pool Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #436
02/11/86
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Ken Yerrick, Dow Corning, memo to Boley, Cooper, Hayes, Rylee, C. Lentz and Weyenberg regarding immunotox Studies." Yerrick states:

It is my understanding that as a result of the recent visit by Jack Dean we are proceeding with the development of protocols to investigate the effects of silicones on the immune system. From my discussions with Lentz and Boley it is also my understanding that Dean agreed to act, in the future, as an expert witness should the need arise. Of course, he will agree to do this if he is given the opportunity to approve the protocol. I believe we should follow this approach as we proceed with the study. I recognize there are some 1986 budget issues, i.e., no funds budgeted for this project.

CITE: KMM 329406. Dow Corning Trial Exhibit List Abstracts

Document #438
04/22/86
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

H. Ratajczak, R. Thomas and J. Fenters, IIT Research Institute, letter to W. Boley, Dow Corning, Proposing research protocol for "Tests of Potential Immunomodulation by Polydimethylsiloxane Gel." Study is estimated to take two years with the final four months used to prepare the final report.

CITE: KMM 369361 - 369377. Dow Corning Trial Exhibit List Abstracts

Document #439
04/29/86
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

In an Infor-Med, Jackie Markham, Natural Y Surgical Specialties, claims that there is overwhelming agreement among ASAPSs members that the less exposure of silicone to the lymphatic system the better because it means less of a load on the immune system. Surgitek and Dow Corning are accused of dumping and "fire-saleing" high-bleed mammary implants which they had advocated for years on the market. CITE: MEI 4237 - 4239.

Dow Corning Trial Exhibit List Abstracts

Document 448
01/00/87
GEL MIGRATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
SHELL DEGRADATION
SILICA
TISSUE REACTION

Z. Glaser writes a brief article or report entitled "Chemistry of Silicones used for breast implants and other soft tissue applications." Glaser discusses the composition of silicone breast implants, gel migration and bleed, and degradation of silicone by the body. He cites two cases where gel migration into the lymph nodes was noted and an "acute serum-sickness-like reaction" occurred 24 hours past implantation, both instances were from intact implants.

CITE: M 780070 - 780073. NOTE: See 01/00/85 entry. See 07/25/88 entry; possible attachment to M 780066 - 780069.

Document #450
01/16/87
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by LeVier to Frye, Lane, LeVier, Skinner, Hobbs, Rylee and Stark titled "Organosilicon Insect Toxicants," report number 6053, series number 10030. A selection of linear siloxanes, siloxane copolymers and cyclic siloxanes were found to posses toxicant activity against crickets, alfalfa weevils, feline fleas and bovine lice. The mode/mechanism of toxicity was not determined. Cost and lack of chemical reactivity preclude use of these structures as agricultural insecticides.

CITE: DCC 2010235 - 2010283.  Dow Corning Trial Exhibit List Abstracts

Document #453
2/23/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
SHELL DEGRADATION
TESTING
TISSUE REACTION

Robert LeVier, Dow Corning, memo to Hayes, Rylee, Stark, Thiess, Weyenberg, and Yerrick regarding the "Medtox Project Final Report." Seven numbered copies of the Medtox Report were issued to the seven individuals listed above. The final report replaces the 12/31/86 interim report. Levier asks each of the recipients to "Please discard the interim report dated December 31, 1986.: (KMM 298339).

The purpose of the Medtox project was to formulate a consolidated understanding of all internally funded safety studies of silicone material relevant to the Health Care Business and to relate the findings to current safety issues as presented in the literature, by the physician community and in litigation. LeVier reviewed four sources of information: the Corporate Toxicology File 1949 - present, the DC 360 Fluid NDA 2702 file 1974, the Medical Research Report File 1980 - present, and the Corporate Mainframe Reference List 1957 - present. The report will generate a database for Dow Corning to search and will be available to the Legal Department. The first and earliest report LeVier noted was a 1949 publication. He also located and identified in the appendix 110 reports. The studies through 1963 were primarily related to antifoam compounds and emulsions used in antigas formulations. Thereafter, the studies were conducted to qualify materials. "Studies in the 1980 - 1986 period are primarily directed toward requalification of materials that have been in use for some time."

Levier concludes that the reaction at the implantation site is an acute inflammation progressing to chronic inflammation characteristic of a mild foreign body response and that there is no evidence of systemic toxicity.

LeVier does note, however, that:

Two studies indicate that PDMS injected S.Q. or I.P. in very large quantities (5 to 62 ml/animal) in mice and rats is disseminated broadly and polymer is microscopically visible as deposits in tissue. It is likely that these deposits are the end-stage result of phagocytic transport and aggregation of polymer....

Several teratology studies in rats and rabbits have shown a positive but low incidence of skeletal defects and increased fetal resorptions.

LeVier acknowledges that silicone fluid and silicone elastomers can be found in macrophages and multinucleated giant cells. "The greater incidence of macrophages and giant cells is more characteristic of a chronic inflammatory state than usually seen around elastomer implants in the absence of abrasion particles." He notes that the silicone fluid migrates and is transported to regional lymph nodes. Further, LeVier concludes that:

The implantation site reaction to silicone gel, particularly in the form of a fabricated mammary prosthesis, is similar to that produced by fluid polymer. In the case of free silicone gel the distribution compared to fluid polymer resides in the cohesiveness of the gel.... In the case of free gel, progressive gel subdivision by connective tissue septa is superimposed on encapsulation of the entire gel mass.

The analyses of the internal studies indicates that there are notable deficiencies among the reports. LeVier classifies these as "Nuisance Issues" and "Substantive Issues." The nuisance issues include that the study designs are outdated, the studies are of limited utility, the variety of systemic histopathologic findings is broad, and the majority of the studies were conducted by IBT and FDRL. "Both of these companies are known to have falsified data in the time period relevant to the studies conducted for Dow Corning." He does not think it likely that any of Dow Corning's studies were falsified, but he does not state the basis for this belief.

Regarding the substantive issues, LeVier states:

There are two specific deficiencies of importance that tend to limit the utility of the long-term studies in particular.

1. The histopathology of the reticuleondothelial system (RES) including liver, spleen, lungs,lymph nodes and bone marrow was not examined carefully or systematically in any long-term study. Therefore, little information is available from these studies with regard to migration of implanted materials nor with regard to target tissue effects. Such an examination is rarely part of a formal toxicity study but the absence of such an evaluation is often cited as a criticism.

2. None of the studies incorporate a critical assessment of physiologic effects induced by the local inflammatory reaction. Nor is the nature of the local reaction assessed in detail. Thus, no information is available with regard to effects on the immune system, for example.

In discussing the limitations of the prior studies, LeVier admits that there are no studies in which the inflammatory reactions were described and classified according to "criteria employed by researchers expert in the study of inflammation nor have any studies been designed to detect the range of systemic effects that could attend a chronic inflammatory state.... Presently, there are insufficient data to effectively understand cause and effect relationships or to defend silicones against the broadening claims of HAD stimulation.:

In discussing what corrective measures should be taken. LeVier recommends that Dow Corning should not replicate any of the studies that were flawed and outdated. He states: 

Replication of existing studies for the sole purpose of correcting nuisance problems would be very costly and would consume several years before results could be available. Some problems such as too few animal per group and too many implants per animal could be corrected but it is improbable that the spectrum of unrelated pathologic events could be materially influenced. It is such pathologic events that are used to claim systemic toxicity caused by silicone implants. The course of action (corrective measure) that is recommended is to develop sound arguments in support of the validity of existing studies. (emphasis added).

LeVier also discusses the immunopotentiation of silicone and notes that "if immunopotentiation is prolonged in response to PDMS, then the probability may be increased that silicone has an adjuvant like effect of sufficient duration to promote development of auto-antibodies in susceptible individuals."

CITE: KMM 298296 - 298339. NOTE? The interim Medtox report is dated 12/31/86. NOTE: Includes LeVier memo sending attached Medtox report to D. Hayes, R. Rylee, F. Stark, G. Thiess, D. Weyenberg and K. Yerrick. Dow Corning Trial Exhibit List Abstracts

Document #455
02/24/87
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE
FRAUD/MISREPRESENTATION

Steinberg, Dow Corning counsel, submits information to the FDA regarding the Two-Year Gel Implant Study of Dow Corning 360 Fluid and the findings of malignant lymphoma.

CITE: KMM 491863 - 491912. Dow Corning Trial Exhibit List Abstracts

Document #456
03/24/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

W. Boley, Dow Corning Wright, memo to Brodhagen, Frisch, Jakubczak, and others regarding "Summary of H.E.S. Testing Activities In Support Of Health Care Businesses For February." The first immunotoxicology testing by Dow Corning is scheduled to begin on April 27. 1987 (25 years after Dow Corning first sold breast implants). The protocol was sent to Dow Corning for approval.

CITE: M 170187 - 170191. Dow Corning Trial Exhibit List Abstracts

Document #459
04/13/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWDEDGE OF SYSTEMIC DISEASE

John Ludington, Dow Corning, memo to Gene Jakubczak. Ludington states:

It has recently come to the attention of Executive Management of Dow Corning Corporation that preliminary indications from a current study, indicate adverse effects of Dow Corning medical grade silicone gels placed into the body of highly sensitive test rats. Our scientific assessment is that this does not represent a human health concern....

A committee is formed comprised of Reed, who will be the President and Chairman, Jenkins who will be the legal counsel to the committee, Rylee, and Stark. He directs the committee to "make appropriate recommendation for future action in light of Dow Corning's legal and ethical responsibilities. This investigation is a top priority matter." Ludington cautions persons not to speculate about these matters with anyone else.

CITE: KMM 302536 - 302537, Exhibit to Ludington Deposition, Exhibit to Reed Deposition, Exhibit to Stark Deposition, Exhibit 23 to McKennon Deposition, and Exhibit 26 to Zimmer Deposition. Dow Corning Trial Exhibit List Abstracts

Document #464
08/05/87
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning summarizes data concerning a Two Year Gel Implant Study in rats conducted by Industrial Bio-Test Laboratories using the old gel - MDF 0193, and responsive gel - Q7-2159A. Dow Corning claims there were deficiencies in the original report such as improper tabulation and evaluation of tumor findings including malignant lymphomas. Hughes Research and Development was asked to review the data and tissue samples and, in their second report, found a treatment-related increase in the incidence of malignant lymphoma. Dow Corning refuted this conclusion claiming that the increase in lymphoma was "stress related viral induced but no basis to substantiate our opinion." Dow Corning subsequently conducted an internal study. An independent panel of experts convened by Dow Corning reviews all data and finds that the implant site sarcomas identified in the studies are predictable due to "solid state" carcinogenesis in rats, a phenomena which allegedly poses no significant risk to human health.

CITE: KMM 491869 - 491881. Dow Corning Trial Exhibit List Abstracts

Document #465
08/13/87
SHELL STRENGTH - THICKNESS
RUPTURE - CLOSED CAPSULOTOMY
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
GEL MIGRATION
TISSUE REACTION

Jakubczak, Dow Corning, sends Dr. Muller a lengthy response to his questions about implant rupture. He states that a hypothetical cause of rupture which may be possible but about which he does not have direct knowledge of is "Excessive force created when closed capsulotomy is being performed." Also, in the event of an implant rupture, gel can migrate and complications include "enlarged lymph nodes, scar formation, inflammation, granulomatous foreign body reaction, presence of foamy histiocytes, silicone mastopathy, nodule formation, or other difficulties.... The long term physiological effects of uncontained gel are not completely known." 

Jakubczak states that Dow Corning has been tracking the rate of ruptures since the gel-filled implants were introduced to the market. "The rate (Of rupture) is less than ).1% for gel filled product. The gel-saline product is slightly less than that for gel product. The SILASTIC II mammary implant, to the best of our knowledge, is in the ballpark or slightly less. For the specific time period of the last 1970's our data indicates that the rate of rupture was the same."

CITE: M 460204. DUPLICATE: KKH 75863 - 75871. NOTE: Jakubczak did have direct knowledge of ruptures occurring with closed capsulotomies. Also, Dow Corning did not track rupture rates like he represents in this letter. Dow Corning Trial Exhibit List Abstracts

Document #468
11/03/87
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE

Dan Hayes, Dow Corning, memo to Frisch, Hobbs, LeVier, Steinberg, the DCW Business Board, Rylee, and Stark regarding the Dow Corning Wright Keratosis Program. Hayes asks, "What is the best approach to deal with silicone migration in this application? How do we approach the immunology issues that have been raised in literature in recent years?"

CITE: DCC 251000386 - 251000387  Dow Corning Trial Exhibit List Abstracts

Document #469
11/17/87
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Complaint Report MW 2030 submitted to Dow Corning regarding a Silastic implant. The patient developed "bronchospastic asthma of allergic nature" related to the silicone. The patient has leakage from her nipples which is suspected to contain silicone. Dow Corning agrees to devise a test to detect whether the discharge was silicone. (emphasis added).

CITE: KKH 72651. Dow Corning Trial Exhibit List Abstracts

Document #473
01/00/88
KNOWLEDGE OF SYSTEMIC DISEASE
FRAUD/MISREPRESENTATION

Hayes, Dow Corning, writes Dear Doctor letter regarding immunological reactions to silicone. He encloses a position paper. The position paper criticizes the research done by the Japanese by claiming that fluids used were often adulterated and by claiming that the adjuvant concept is broadly misunderstood. The paper gives a brief description of the research that has been done on the problem and then states:

Unfortunately, all animal studies reported to date have been founded upon incomplete experimental designs, and interpretations and speculations that extend well beyond the support that can be provided by the data.

CITE: KMM 122710 - 122712. DUPLICATE: MD 145633 - 145635.  Dow Corning Trial Exhibit List Abstracts

Document #474
01/22/88
KNOWLEDGE OF LIQUID SILICONE DANGERS
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Frisch, Hobbs, LeVier, and Steinberg, Dow Corning, author a report "keratosis Program Team Report." One of the issues this team has identified is to negotiate an IDE program with the FDA that would allow Dow Corning to do only short-term evaluations of silicone fluid injections for keratosis" without the requirement for extensive clinical and laboratory studies." The silicone to be injected is Dow Corning 360 Fluid. The team assumes that, "Prior studies sponsored by Dow Corning (carcinogenic, reproductive and developmental) will not suffice. The protocols and designs of prior studies were not adequate by today's standards, and in some studies the findings left unanswered questions."

The team notes that bioassays which must be addressed include carcinogenic, pharmacokinetic and immunologic. "Immunologic studies are not on the FDA general list and are not included in projected costs, but because of the current flurry of publications alleging immunogenic reactions to silicones FDA may want these studies done. Internally, evaluation of the immunogenic potential of silicone fluids is currently being planned, and it is believed these data would apply to 360 fluid even if the fluid involved in the study were 200 fluid."

Furthermore, the team states:

FDA will probably require adequate data to assure safety prior to allowing the clinical investigation to proceed. FDA's concerns will most likely center on carcinogenicity and reproductive/developmental toxicity issues. Dow Corning currently has neither human nor animal data to address these issues in a statistically valid, scientific fashion. The reproductive/developmental toxicity issue could perhaps be temporarily waived by not including women who may have children, but this still leaves the carcinogenicity issue unresolved. (emphasis added).

CITE: KMM 407502 - 407540.  Dow Corning Trial Exhibit List Abstracts

Document #478
03/25/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Board of Directors' meeting showing a report that early test results show that D4 has a toxic effect on daphnia in low concentrations and that further testing is planned.

CITE: DCC 101003623 - 101003626, Exhibit 10 to McKennon Deposition, and Exhibit to Weyenberg Deposition.

Document #484
08/09/88
TESTING
CONCEALING FROM FDA
KNOWLDEDGE OF SYSTEMIC DISEASE

FDA: M. Stratmeyer, Acting Chief, Health Sciences Branch of FDA to Director, office of Science and Technology, memo with attached report regarding analysis of Dow Corning data on carcinogenicity of silicone gels. "As you will see, the conclusion of this report is that silicone can cause cancer in rats; there is no direct proof that silicone causes cancers in humans; however, there is considerable reason to suspect that silicone can do so." The FDA Reviewer finds that patients were studied for an average of 6.2 years which is "probably too short to detect breast cancer... considering that the latency period for foreign body carcinogenesis in humans appears to be in the range of 20-30 years."

CITE" M 780055. DUPLICATE: FDA 29449 - 29457.   Dow Corning Trial Exhibit List Abstracts

Document #485
09/23/88
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Dr. Selwyn, Statistics Unlimited, Inc., prepares a "Statistical Analysis for Two-Year Gel-Implant Study of Q7-2159A and MDF-0193 in Sprague Dawley Rats (M8518-0)" for Dow Corning which concludes that "Carcinogenesis is noted in mammary gels in significant amounts." (KMM 388066 - 388150: KMM 2726331 - 272637). Histopathological analysis demonstrated "increased incidences of fibrosarcomas at the implant site which were highly significant for both the Q7-2159A group and the MDF-0193 group, and in both sexes." Incidences of non-neoplastic findings were statistically greater in the Q7-2159A group males than in the control group for the following: "chronic capsular inflammation, implant site dysplasia, fibrous capsule at the implant site, implant site necrosis, extracapsular gel, acute and chronic pyelitis, necrosis in the liver, seminal vesicle secretion (reduced or absent), stomach necrosis, and thymic region hemorrhage."

CITE: KMM 388067 - 388150. DUPLICATE: KMM 272631 - 272637. Dow Corning Trial Exhibit List Abstracts

Document #488
12/14/88
TESTING
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE
ACKNOWLEDGEMENT OF NEED FOR TESTING
SILICA

John Yan, Mentor, reports on his trip to Dow Corning. He notes that Dow Corning uses the Statistical Process Control Method to assure product reliance. Mark Zimmer, Dow Corning's veterinarian, presents Dow Corning's internal study on the two-year rat study. (No reference is made to IBT's or Hughes Research findings nor to other "expert" panel and their recommendations.) "Dow Corning found the test animals to develop dysplasia, chondrosarcoma, fibrosarcoma, and sarcoma.... (T)hey found a 52% incidence of site related tumor formation with the rats and 24% incidence with the female rats." Yan notes that Dow Corning purchases all of its fumed silica from Cab-o-Sil.

Yan also notes that, "At present, teratogenicity, immunological, and pharmacokinetic studies have not been initiated on the gel." (emphasis added). Dow Corning did not share with Mentor the Master File for the Gel.

CITE: MMD 167731 - 167733.  Dow Corning Trial Exhibit List Abstracts

Document #490
03/01/89
TESTING
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Siddiqui, Kolesar, Zimmer, and Hobbs, Dow Corning, report on "A 90-Day Sub-Chronic Inhalation Toxicity Study Of Octamethylcyclotetrasiloxane (D4) In The Rat." Exposure resulted in slight growth retardation and lower food consumption in females. There was also an increase in liver weights that was statistically significant, leading the authors to conclude that "these data indicate that D4 has an effect on the liver."

CITE: T 40150 - 40276, Exhibit 34 to Zimmer Deposition. DUPLICATE: KKP 15029 - 12155. Dow Corning Trial Exhibit List Abstracts

Document #493
05/22/89
SILICA
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD

LeVier, Dow Corning, memo to Birdsall, Steinberg and Groh regarding "Risk Assessment: Carcinogenic Potential Of Silicone RTV Elastomers And Foams Containing Celite Super Floss Or Celite 315 Fillers." Attached is the first draft of a risk assessment overview necessitated by the recent discovery that the supplier of silica had been using cristobalite and other crystalline silicas in materials that comprise the elastomer. LeVier states:

"The majority of health care elastomer products employ amorphous silica as the reinforcing filler. These fumed amorphous fillers have been shown by X-ray defraction analysis to contain no crystalline fraction. However, RTV's in the form of elastomers and foams are based on older tin catalyzed formulations that use Manville Celite Super Floss (CAN#: 68855-54-9) or Cilite 315 (CAN#:61780-53/2) as the reinforcing filler (MSDS's attached). These silicas are generically classified as flux calcinated diatomaceous earth. It has recently been learned from the silica manufacturer that Celite Super Floss contains up to 63% cristobalite and Celite 315 contains up to 23% cristobalite. Cristobalite and other crystalline silicas have been classified by the International Agency for Research on Cancer (IARC) as probably carcinogenic for humans." (emphasis added)."

The products affected by this discovery include 382 Medical Grade Elastomer which was discontinued in 1987: "for economic reasons related to additional safety testing required to investigate the availability and effects of stannous octoate catalyst degradation products (the subject of a 1987 Risk Assessment).... This product was sold to many other manufacturers and individual physicians.... Dow Corning has also recently licensed the 382 technology to the World Health Organization (WHO) for the purpose of manufacturing and selling a contraceptive vaginal ring. Dow Corning's supply position in the later application has not yet been fully defined. The cristobalite component in these materials ranges from about 10 weight percent to 30 weight percent. The highest concentration of crystalline silica occurs in 382 Medical Grade Elastomer."

LeVier reviews the Dow Corning data on stannous octoate RTV formulations and concludes that "there are no long-term animal implantation data available." The human data from inhalation studies of silica show that "crystalline silica can increase the incidence of lung cancer.... There is sufficient evidence for carcinogenicity of crystalline silica to experimental animals. There is limited evidence for the carcinogenicity of crystalline silica to humans." LeVier’s risk assessment conclusions are that:

1) Unmodified crystalline silicas including cristobalite-containing silicas are probably carcinogenic for humans via inhalation exposure. The probability that crystalline silicas are carcinogenic for humans via parenteral exposure is less certain but existing animal data indicates that such silicas administered parenterally may be carcinogenic for humans....

4) The effect of in situ plasticizer treatment of Celite silicas on their possible carcinogenicity is unknown except on a theoretical basis. Theoretical considerations lead to the prediction that treated crystalline silicas could be less carcinogenic than unmodified crystalline silicas....

6) "An (sic) life-time rat study of the potential carcinogenicity of treated Celite silicas cannot provide unequivocal proof that such silicas cannot be carcinogenic for humans.

CITE: KKA 1601 – 1608 Dow Corning Trial Exhibit List Abstracts

Document #496
12/04/89
CONCEALING FROM FDA
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

515(B): Dr. Jack Fisher (ASPRS) informs "All Members of BIRAC, Old and New" about progress report since ASPRS convention in San Francisco. He notes four concerns of the PSEF Board of Directors and those of BIRAC: 1) that manufacturers had written the RFP and they thought Colton was going to do this; 2) concerned that all southern California bidders would be excluded; 3) concerned that one manufacturer stated that it would only fund two issues from a longer list that PSEF wanted studies; and 4) concerned and "disappointed that the study does not address the connective tissue issue.... Based on our very best clinical judgment and scientific understanding, we believe that CT disease issue will forever loom until we meet it head on." (emphasis added). PSEF is also deeply concerned about the reporting requirements - the potential delays in notification of study results. PSEF believes "these restrictions to be an infringement of academic freedom and a potential embarrassment to foundation (PSEF)."

CITE: KKA 43763 - 43769A. Dow Corning Trial Exhibit List Abstracts

Document #497
01/31/90
TESTING
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Crofoot, Stanton, Siddiqui, and Zimmer, Dow Corning, report on "A 14 - Day Subchronic Oral Gavage Study With Hexamethylcyclotrisiloxane In Rats." Oral administration of the test material, D3, "may produce increases in liver weight at dose levels as low as 100 mg/kg and perhaps as low as 25/kg in the male rat...." The authors state that the "toxicologic significance of the liver weight increases cannot be made."

CITE: T 37322 - 37409, exhibit 36 to Zimmer Deposition. DUPLICATE: T 37447 - 37490.  Dow Corning Trial Exhibit List Abstracts

Document # 502
08/13/90
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE
DOCUMENT DESTRUCTION

FDA: B. Levier, Dow Corning, memo to R. Dieck and L. Duel regarding Statistical Analysis of Neoplasm Data from 2 Year Gel-Implant Study of Q7-2159A and MDF-0193 in rats stating, "but the sum of hepatocellular adenomas and carcinomas is within only one or two tumors of being statistically significant.... Our argument... may still be plausible but it is weakened by these findings... (and) I think it would be imprudent to test this issue with the FDA." A handwritten note at the bottom of the memo states "Please discard this memo after reading." (emphasis added).

CITE: KMM 451517 - 451525.  Dow Corning Trial Exhibit List Abstracts

Document #507
12/06/90
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE 

Robert Rylee, Vice President and General Manager of the Health Care Business of Dow Corning, sends a "Dear Doctor" letter. Rylee states that Dow Corning "voluntarily" submitted information to the FDA including a "summary list of 750 bio-safety studies and full reports of more than 30 toxicology studies.... The list included all of our studies; none were withheld." Rylee discusses recent media attention and a 11/27/90 decision by a district court in Washington D.C. ordering Dow Corning to make public this bio-safety data.

Dow Corning cites the need for confidentiality as the reason it is appealing the district court's order.

Rylee also states that there have been recent reports of immunological responses to silicone breast implants. "Suspected immunological response is a controversial subject because there are so few cases available for study. A review of the global literature indicates that out of more than two million women with silicone mammary implants, only about 40 have been reported to have a form of rheumatic/connective tissue disease. Some form of scleroderma has been reported in 14 implanted women with a latency of about 10 years, and so-called human adjuvant disease HAD) has been reported in 13 implanted women with a latency of about 7 years." He concludes by states that based on Dow Corning's 25 years of experience in silicone breast implants has demonstrated the "reasonable safety and efficacy of these devices."

CITE: M 370276 - 370277, Exhibit to MDL Rathjen Deposition. DUPLICATE: M 690014 - 690014A.  Dow Corning Trial Exhibit List Abstracts

Document #511
12/14/90
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Hazleton memo to various personnel regarding the establishment of a Steering committee Team to manage the evolving issues and communications surrounding the biosafety of D4 and other small molecule dimethyl materials. The team will be comprised of Bill Cavanaugh, Barie Carmichael, Chuck Dillon, Deb Zellner, Doug Wernecke, Mark Zimmer and Jack Pulley.

CITE: No Bates Number; Exhibit 3 to Boley Deposition, and Exhibit 33 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #517
01/28/91
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Zimmer, Dow Corning, memo to Co-Producers Technical Committee and Co-Producers Steering Committee regarding documents to review for February technical committee meeting. Zimmer states that the draft reports of the previous morphometrics and DNA studies indicate that it is fair to say that D4 causes hepatocellular hyperplasia and that no evidence of hypertrophy was evident. He also enclosed morphometrics and DNA assay protocols for a 2-year rat bioassay and for cell replication studies.

CITE: DCC 260000566, Exhibit 39 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #520
03/12/91
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

Stark, Dow Corning, memo to Lentz regarding the proposed modification of future D4 testing programs. Stark states that the morphometric and DNA studies are technically sound and correctly interpreted, the ovary weight issue must be resolved, pharmocohinetics and additional metabolism data are imperative before we embark on reproduction, teratology, and chronic studies, and cell replication studies must precede chronic studies. Stark encloses an outline of the proposed D4 research plan.

CITE: DCC 260000706 - 260000716, Exhibit 42 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #521
03/15/91
FRAUD/MISREPRESENTATION
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE

Woodbury, Dow Corning, letter to Gary Brody, M.D., regarding National Health Statistics Survey. Woodbury states:

Factors which may influence the accuracy of prevalence estimates: 

--Primary data collection methodology.

--Statistical design of sampling plan.

--Specific data collection methodology within a given primary data collection method.

--Survey participation bias.

--Completeness or representativeness of data upon which estimates are based.

--Analysis Method.

--Willingness of respondent to disclose information or knowledge and willingness to disclose for a proxy respondent.

--Device replacement rates and frequency of replacement.

--Permanent removal rates.

--Mortality patterns for implanted patients.

--Device inventory and wastage for marketing based estimates.

--Subjective estimates of surgery rates by surgeons within surgeon surveys.

 The letter includes an attachment containing a comments by R. Delongchamp, Dow Corning, stating:

"The observation of serious disease among women with cosmetic implants is expected simply because all women eventfully die whether or not they have an implant. As the numbers of women with implants increases, this fact makes it inevitable that at least one woman with an implant will succumb to even the rarest of diseases. An assessment that the implant caused the disease is unwarranted."

 The letter also includes attachments presenting survey data.

CITE: KMM 403500 - 403530, Exhibit to Harris County Rylee Deposition, Exhibit 17 to Woodbury Deposition. DUPLICATE: KKA 102860 - 102880. Dow Corning Trial Exhibit List Abstracts

Document #522
05/01/91
ACKNOWLEDGEMTN OF NED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Ruhr and Hoffman titled "Progress Report: A Chronic Implant Study In Rats With Dow Corning Q7-2423 and Q7-2551 Elastomers," Dow Corning Tox file 3810-10 and 5194-8. These silicone elastomeric materials comprise the envelope for the Silastic II and silastic MSI mammary prostheses.

Four groups of 60 male and 60 female rats each are incorporated into the study design. There is a sham operated control group, a U.S.P. polyethylene control group, and one group for each of the elastomers.

Statistical analysis will be performed on body weight and food consumption data; organ weight; and appropriate clinical pathology data.

CITE: P 19120 - 19163, Exhibit 21 to Zimmer Deposition, Exhibit 5 to Bejarano Deposition, Exhibit 1 to Bey Deposition, and Exhibit 36 to McKennon Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #533
02/11/92
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - LOBBYING

Zellner, Lutz, McClintick, Rothhaar and Clary, Dow Corning, memo to Parr, Yerrick and Anderson regarding D4 issue definition and actions. The authors present an overall communication plan that is split into two phases. Phase I is to disseminate the most recent information regarding the orally administered, range-finding study on rabbits. Phase II is to assure a state of DC preparedness to effectively meet any/all future D4-related events and provide a mechanism for periodically updating customers regarding D4 study plans and results. The authors enclose a schedule for each phase.

CITE: DCC 260000852 - 260000854, Exhibit 43 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #535
02/13/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Klykken, Dow Corning, memo concerning "Differentiation Of Foreign Body Reactions And Immune Granulomas." Klykken gives a brief overview of foreign body reactions - which he claims are a "normal wound healing response" - and immune reactions to the implant which could range from "mild, fleeting symptoms to severe disruption of immunoregulatory functions and premature removal of the medical device." He claims that Dow Corning scientists "have failed to demonstrate any linkage between these implant materials and immunological sensitization."

CITE: M 850018. NOTE: Eldon Frisch, Dow Corning, admitted in memos dated 11/15/89 that Dow Corning had not done any immunological testing but needed to do so.  Dow Corning Trial Exhibit List Abstracts

Document #536
02/24/92
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING

Joan Hatfield, Dow Corning Australia, fax attaching several documents, notably:

a. Dow Corning 02/10/92 press release announcing the release of "15 reports of scientific studies and 94 internal, non-scientific company documents." In the release, Rylee admits implants are not risk-free. Tylee quotes Dr. Calman of the United Kingdom Department of Health stating: "There is little evidence on links between silicone gel implants and autoimmune disease."

b. McKennon 02/11/92 letter expressing regret that the "10 or so most painful memos" to be used against Dow were taken out of context, "to discredit Dow Corning," often without concern for any responsive documents or memos. Also, McKennon feels that "many of Dow Corning's critics are applying 1990's standards to 1970's memos and studies." McKennon also states that he has been assured that all of the information known to Dow Corning which might be relevant to their deliberations has already been provided to the FDA.

CITE: DCC 267010007 - 267010014.  Dow Corning Trial Exhibit List Abstracts

Document #538
03/09/92
COHESIVENESS - LIQUID COMPONENT OF GEL
FRAUD/MISREPRESENTATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Lutz, Dow Corning, memo to Clary, McClintick, Klykken, Rigas, Roghhaar and Zellner regarding position statement on gel bleed and D4 - review and comments. Comments regarding bleed include bleed of silicone fluid is commonly associated with mammary implants and has long been recognized by surgeons as a characteristic of silicone gel-filled breast implants. The amount of bleed is largely dependent on the molecular weight of the silicone material. The comments regarding D4 include that it is contained in minute quantities in the silicone gel-filled mammary implant and Dow Corning and other manufacturers believe D4 is safe for use in its intended applications and in no way affects the safety of silicone mammary implants.


CITE: KMM 452997 - 453002, Exhibit 44 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #539
03/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Memos updating latest D4 study results. One study showed that pregnant rabbits will stop eating and show a significant weight loss. Non-pregnant rabbits will do the same. Another study has shown that there are effects on certain internal organs, organ effects can be expected whenever there is significant weight loss. It is believed that Dow Corning's exposure guidelines and work practices for D4 continue to provide adequate protection for all employees.

CITE: DCC 17030046 - 17030047, Exhibit 15 to Zimmer Deposition, and Exhibit 4 to Boley Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #542
03/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Harrison memo to S&T plant personnel regarding an update of D4 study findings. 

CITE: DCC 17030046 - 17030047, Exhibit 15 to Zimmer Deposition.  Dow Corning Trial Exhibit Lost Abstracts

Document #543
04/24/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - PRODUCT LABELING
TESTING
TISSUE REACTION

Rothhaar, Dow Corning, memo to Product Safety and Regulatory Compliance Staff regarding D4 material safety data sheets and labels. Rothhaar states that there is a moratorium on changes to material safety data sheets and labels for products containing D4 and D5. The reason for this moratorium is because the increased liver seen in some test animals exposed to D4 is believed to be an adaptive response rather than a true toxic effect and it is appropriate to retain the current 10 ppm industrial hygiene exposure guideline.

New products will not show D4 listed in the MSDS unless the D4 contributes to the product being a physical hazard and if not listed, no statements regarding the liver effect information and no mention of the IHG will be included in the MSDS but will be listed if it is determined to be hazardous. In any case the label for the product will not include any health hazard warnings relating to D4. There will be no potential liver effect statement on the label.

CITE: DCC 260000772 - 260000774, Exhibit 53 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #546
07/14/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Memo from Forrest Stark to the Environment, Health & Safety (EHS) Board which consists of Gary Anderson, Bey, Crossman, Foglesong, Harrison, Lacefield, LeVier, Pulley, Weyenberg and Yerrick. Copies of the memo were sent to D. Anderson, Bassani, Birdsall, Churchfield, Dover, Frye, Grupp, Haberer, Hayes, Hazleton, Hoover, Jenkins, Kabbe, Ludington, Marciniak, McCormick, Nishio, Parr, Pfuehler, Reed, Rothhaar, Skinner, Snedeker, Steinhoff, Ziarno, Roth, Zimmer and Groh. The memo discusses "Environment, Health & Safety Board Meeting Minutes Meeting Held June 30, 1992."

CITE: DCC 17003795 - 17003829, Exhibit 18 to Zimmer Deposition. NOTE: This contains overhead presentations on D4 which are very interesting.  Dow Corning Trial Exhibit List Abstracts

Document #547
09/07/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning lists "Clinical Immunology Proposals...and finds worthy of serious consideration:

1. Barrett Noones's silicone as an antigen and =/-presence of specific antibodies; specific T-cell stimulation; Dow Corning states that this "becomes important in the light of the recent Goldblum article";

2. Walter Peter's cytokines in implanted individuals. He has already started screening individuals and Myron Harrison, Dow Corning, has asked him to combine this clinical study with Laurence Rubin's proposal on serologies on implanted women to look for markers of autoimmune disease.

3. James Sanger's proposal to study the presence or absence of humoral antibodies contiguous to implants or in case of rupture.

4. Kimber White's (study on the potential immunogenicity of silicone elastomers and elicitation of humoral or cell-mediated responses.

5. Daniel Ladin's and David Fivenson's study hyupothesis that T cell activation occurs at the site of capsular formation and that peripheral blood lymphocytes have the same oligocloanality.

6. Howard Smith's study on indiciduals who are being explanted and claims to be seeing differences in some biomarkers levels.

7. Marianne Frieri"s clinical immunology focusing on cytokine and growth factor assessment in breast implant patients.

8. Robert Winchester's and Jane Morse's characterization on the clinical features, auto-antibody profile, lymphocyte phenotypes, and HLA groups of women who are symptomatic post implant.

9. Nemecek Young's clinical research with emphasis on immunology and genetics.

10. Sudha Agarwal's and Marc Liang's study on immune response to silicone implants.

11. John Varga's clinical studies.

12. Jeffrey Brown's rupture detection via MRI.

13. M.A. Atassi's clinical immunology and animal studies of the immune system.

CITE: DCC 267011492 - 267011512. Dow Corning Trial Exhibit List Abstracts

Document #548
10/19/92
ACKNOWLEDGEMETN OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING 

Minutes of the Substantial Risk Evaluation committee Meeting. The committee considered the risk associated with D4 and determined that the single high dose had a toxic effect on the tested animals and therefore the other observations are not necessarily indicative of an immune system effect, insufficient data is available to determine a dose-response relationship but there is no reason to suspect that actual exposure to D4 would cause the effects noted, the method of exposure in this study is not expected in real-world situations so the risk of these results being seen in actual exposed populations is slight, and even if people exposed to D4 had similar effects as noted in the study there is no substantial risk because the effects would be transient or reversible and not result in serious effects.

CITE: DCC 281061443 - 281061450, Exhibit 47 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #549
12/31/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
GEL MIGRATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
MISCELLANEOUS - LOBBYING
RUPTURE
TESTING
TISSUE REACTION

The Committee on Government Operations (John Coyners, Chairman, Henry Waxman, et al.) writes a report which includes a scathing critique of the FDA's failed regulation of silicone breast implants while ignoring their own scientists recommendations and the manufacturers' failure to do any long term safety studies. Silicone breast implants should have been banned due to lack of safety evidence in all manufacturers PMA's. The article covers all areas of this issue.

CITE: PSSC Medical Articles CD, J 3968 - 4022.  Dow Corning Trial Exhibit List Abstracts

Document #550
12/09/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - ORGANIZATIONAL SURVEY

Bey memo regarding industry associations, silicone health council (SHC) history, SHC/GSPA meeting objectives - D4 program, Dow Corning position SCH/GSPA meeting November 9012, 1992 - D4 program, global silicone producers association - committee chairs and current members, and SCH/GSPA meeting results - D4 program.

The Silicone Health Council was founded in the mid-1970's by Dow Corning, General Electric and Union Carbide. It was managed via the Industrial Health Foundation at the University of Pittsburgh. Wacker Silicones and Rhone Poulenc joined SHC in the 1970's. In the 1980's, SHC was affiliated with SOCMA, Wm. Smock, Director. In the 1990's, Shin-Etsu Chemical, PCR, Huls, and Goldschmidt joined SHC.

CITE: DCC 17003711 - 17003719.  Dow Corning Trial Exhibit List Abstracts

Document #551
01/07/93
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEIOUS - COMPLICATIONS
TESTING

Zellner, Dow Corning, memo to Area S&T Directors regarding updates on D4 studies. Zellner states that studies indicate that D4 is safe for the use as a cosmetic ingredient, D4 has a very low toxicity level and that Dow Corning retain the Industrial Hygiene Guideline of 10 ppm for D4 and D5. Zellner insists that these studies were conducted by an independent group of scientists.

CITE: DCC 17005456 – 17005457.  Dow Corning Trial Exhibit List Abstracts

Document #553
03/22/93
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

FDA: An FDA Talk Paper references two studies that show silicone gel can act as an antibody adjuvant. This supports the causal relationship between silicone gel-filled breast implants and autoimmune disorders.

CITE: BMS 68289 – 68291. Dow Corning Trial Exhibit List Abstracts

Document #555
06/14/93
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Crofoot, Kolesar and Evans regarding an acute and repeated dose inhalation toxicity study with Dow Corning Z-6228 silane in albino rats.

The results of this study indicate that Dow Corning Z-6228 most likely will not present a significant acute inhalation hazard. However, repeated exposures may cause injury of respiratory tract under the conditions of this study. It is recommended that further toxicological studies be conducted to investigate the effects of long-term exposure.  

CITE: DCC 411000178 - 411000230 (Temporary Dow Corning Bates Number 178 -230); Exhibit 7 to Bejarano Deposition; Exhibit 6 to Bey Deposition, and Exhibit 22 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #556
07/20/93
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Kolesar, Hoffman, Crofoot, Kowalski. Siddiqui, Evans and Groh regarding a two-week repeated dose inhalation toxicity study of hydrogen chloride and selected chlorosilanes in albino rats.

The results of this study showed no differences between gaseous hydrogen chloride and Me3SiC1, Me3SiC13, and MeSiC13. However, microscopic examination revealed mineralization in the kidneys of females exposed to HSiC13. Whether or not this lesion represents an earlier age-related predisposition to development is not known.

CITE DCC 411000141 - 411000157; Exhibit 6 to Bejarano Deposition; Exhibit 7 to Bey Deposition, and Exhibit 23 to Zimmer Deposition.  Dow Corning Trial Exhibit List Abstracts

Document #557
09/01/93
TESTING
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE

Malczewski, Woolhiser, Mudget, Duwe, Galbraith, Nash and Klykken, Dow Corning, report on "A Humoral Adjuvancy Study In The Rat Of Dow Corning Silicone Gel (Q7-2159a) Preparations And Mammary Gel Bleed." All three sheared mammary gel/BSA preparations demonstrated comparable antibody responses to the positive FCA/BSA control and were significantly greater than that of the non-adjuvant control at 4, 6, and 8 weeks post-immunization. The ability of sheared silicone gel preparations to elicit an adjuvant response does not appear to be a preparation-dependent phenomenon under the conditions of this assay. The adjuvancy potential of mammary gel may not be primarily dependent on the preparation technique. Mammary gel bleed did not elicit an adjuvant response following i.m. administration. The antibody levels generated from this group were equivalent to the non-adjuvant control at all time points measured.

CITE: OOT 48639 - 48655, Exhibit 9 to Klykken deposition in Harris County.  Dow Corning Trial Exhibit List Abstracts

 

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