CONCEALING FROM FDA FRAUD/MISREPRESENTATION

11/15/65 EMBOLISM KNOWLEDGE OF LIQUID SILICONE DANGERS

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

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

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

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

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

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

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

CITE: M 360096 - 360141.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #66

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

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

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

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

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

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

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

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

CITE: KKM 31076 - 31087.

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Document #68

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

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

CITE: KMM 31074 - 31087.

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Document #69

09/06/66 MISCELLANEOUS - ORGANIZATIONAL SURVEY

Minutes of the Board of Directors' Meeting for Dow Chemical Company with a reference to a secrecy agreement with Dow Corning Corporation regarding the biological properties of silicones.

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

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Document #70

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

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

CITE: KKA 7168, Exhibit to D. McGhan Deposition.

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Document #71

10/12/66 MISCELLANEOUS - COMPLICATIONS MISCELLANEOUS - SALES STERILIZATION/CONTAMINATION TESTING

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

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

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

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #72

01/10/67 ACKNOWLEDGEMENT OF NEED FOR TESTING TESTING

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

CITE: DCC 281041120.

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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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 KMM 407480 - 407482). NOTE: See 12/31/87 entry in Master Timeline.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #75

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

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

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

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

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Document #76

03/10/67 MISCELLANEOUS - COMPLICATIONS TESTING TISSUE REACTION

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

CITE: DCC 281041861 - 281041863.

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Document #77

03/14/67 TESTING

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

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

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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.

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Document (On PLAINTIFF'S LITERATURE LIST)

(this is between #78 & #79)

04/00/67 (ON PLAINTIFF'S LITERATURE LIST)

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

CITE: PSC Medical Articles CD, J 157 - 166.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #79

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

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

CITE: P 13605 - 13611.

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Document #80

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

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

CITE: T 1064 - 1103 (Referenced in KMM 407480 - 407482). NOTE: See 12/31/87 entry. DUPLICATE T 996 - 1029.

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Document #81

07/19/67 MISCELLANEOUS SILICA STERILIZATION/CONTAMINATION

"Dip Coated Mammary", project no. MD-50 by P. Lange, L. Crusen. This report constitutes the final phase in the transfer of Medical Development Project No. 50, dip Coated Mammary, to the Medical Products Plant. This report contains the raw material specifications, formulations, manufacturing procedures, formulation specifications and the dip coating procedure and specifications..

CITE KMM 320434 - 320454.

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Document #82

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

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

CITE: GEG 8984 - 8986.

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Document #83

10/18/67 TESTING

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

CITE: KMM 337147.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/privileged & Confidential

Document (NOT ON PLAINTIFF'S EXHIBIT LIST)

(this is listed between #83 & #84)

10/30/67 (NOT ON PLAINTIFF'S EXHIBIT LIST)

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

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

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

CITE DCC 204001107 - 204001108.

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #84

11/10/67 MISCELLANEOUS - COMPLICATIONS TESTING TISSUE REACTION SILICA

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

CITE: DCC 281041072 - 281041074.

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Document #85

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

Food and Drug Research Laboratories issues its report to Dow Corning Corporation, "Studies of the Effects of Injected Dow Corning 360 Fluid In Dogs." Fifteen beagles were subcutaneously injected with Dow Corning 360 fluid in the scapular region for ten successive days. There was a shifting of the injected mass, signs of mange, fluctuations in weight, elevations of the hemoglobin concentrations, differentials in the leukocytic counts, congestion and changes in all organs. One of the beagles died with congestion of the liver, kidneys and heart accompanied with hemorrphagic changes in the lungs and the adrenals.

CITE: T 1202 - 1209, Exhibit to Petratis Deposition. DUPLICATE: T 1251 - 1302; KKH 8185 - 8290; FDA 33172 - 33227; F28 -79.

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Document #86

01/04/68 MISCELLANEOUS - ORGANIZATIONAL SURVEY

Minutes of the Board of Director's Meeting of Dow Chemical Company with a reference to loans and advances made to Dow Corning Corporation.

CITE: TDC 11702 - 11703, Exhibit to Bennett Deposition, and Exhibit to Julius Johnson Deposition.

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Document #87

02/20/68 KNOWLEDGE OF LIQUID SILICONE DANGERS

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

CITE I 470. Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #88

02/28/68 KNOWLEDGE OF LIQUID SILICONE DANGERS GEL MIGRATION

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

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

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

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

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #89

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

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

CITE: DCC 101001529 - 101001543, Exhibit to Bennett Deposition, Exhibit to Julius Johnson Deposition.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #90

04/22/68 TESTING TISSUE REACTION

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

CITE: T 1467 - 1528.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #91

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

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

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

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

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

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

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #92 & #93 05/23-24/68 (this is listed as #92 & #93)

ACKNOWLEDGEMTN OF NEED FOR TESTING MISCELLANEOUS - COMPLICATIONS TESTING TISSUE REACTION

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

CITE: DCC 281041054 - 281041059.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #94

05/31/68 TESTING TISSUE REACTION

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

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

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

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

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

CITE: KMM 104968 - 105041.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #95

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

Dow Corning completes a study of the biological distribution of dimethylpolysiloxane in adult male mice. Significant amounts of radioactivity were found in the tissues and body fluids analyzed. The level of absorption and the biological distribution of the radioactivity were not dependent upon the molecular weight distribution of the fluid or the method by which the fluids were administered.

CITE: DCC 281001381 - 281001399, Exhibit to Harris Country LeVier deposition, Exhibit 3 to Harris Country Rathjen Deposition, Exhibit 19 to Harris County Zahalsky Deposition, Exhibit to Harris County Tyler Deposition, and Exhibit to Weyenberg Deposition.

DUPLICATE: M 100155 - 100174; DCC 242031103 - 242031121; FDA 43184 - 43202.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #97

08/08/68 GEL MIGRATION TESTING TISSUE REACTION

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

CITE: FDA 28545 - 28547. NOTE: See 09/24/68 entry.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #98

10/09/68 KNOWLEDGE OF LIQUID SILICONE DANGERS GEL MIGRATION

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

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

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

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #99

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

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

CITE: DCC 218041771 - 281041776, Exhibit to K. Olson Deposition, and Exhibit to LeVier, Deposition.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #101

01/29/69 SHELL STRENGTH - THICKNESS RUPTURE G. Robertson, Dow Corning, memo to Koning regarding a mammary implant ruptured 1 1/2 years after implantation which was returned by Dr. Crosby. Robertson states, "(T)he envelope edges adjacent to the rupture, appeared to be of a very low tear strength. The physical properties of this envelope may never have been adequate." (emphasis added).

CITE: KKH 1654.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #103

06/10/69 MISCELLANEOUS - COMPLICATIONS TESTING TISSUE REACTION

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

CITE: DCC 281041112, Exhibit to McHard Deposition, Exhibit to K. Olson Deposition, and Exhibit to LeVier Deposition.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #104

07/15/69 KNOWLEDGE OF LIQUID SILICONE DANGERS GEL MIGRATION

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

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

Document #105

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

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

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

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

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

CITE: DCC 16000002 - 160000014, Exhibit 2 to Isquith Deposition, Exhibit 3 to D.McGhan Deposition, Exhibit to Blocksma Deposition (used by plaintiffs and Dow Corning), Exhibit to LeBeau Deposition, Exhibit to Bennett Deposition, Exhibit to Boley Deposition, and Exhibit to Julius Johnson Deposition

WITNESS: "Bennett (Authenticated in Isquith, Vol. I, 119-120).

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

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

CIT: TDCH 1275 - 1276.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

Dow Corning axhibit to McHard Deposition and Exhibit to K. Olson Deposition.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #63 10/27/65 ACKNOWLEDGEMENT OF NEED FOR TESTING COHESIVENESS - LIQUID COMPONENT OF GEL GEL MIGRATION

CITE: M 700003; M 700008 - 700009. DUPLICATE; M 370049 - 370052; M 370108 - 370109; M 370113 - 370114; KKH 62679 - 62682; M 700019 - 700020.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #109

09/20/76

Hobbs, Dow Corning, memo to Hinsch with a copy to Lentz regarding information concerning migration of silicone gels. Hobbs states that experimentation had not demonstrated migration of Dow Corning mammary gel but this factor does not appear to be true for all silicone gels. Hobbs further states that gels having a low consistency due to low levels of cross-linker appear to migrate along tissue planes in much the same manner as large injected doses of silicone fluid.

CITE: M 170104, Exhibit 130 to Burda Deposition; Exhibit 91 to Braley Deposition. DUPLICATE: M 570060. NOTE: The document was listed as 00/00/70 on Plaintiff's Trial Exhibit List.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #110

01/12/70 KNOWLEDGE OF LIQUID SILICONE DANGERS GEL MIGRATION

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

CITE: T 2881 - 2885. NOTE: The report itself was an Exhibit to the K. Olson Deposition (KKH 9841 - 9845). This document also has the Bates number OOM 321368 - 321672 on it. Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #111 02/02/70 STERILIZATION/CONTAMINATION

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

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

CITE: KMM 234056 - 234057.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #112

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

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

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

In the rabbits that had PMS administered orally for eight months, there was a "trend toward decreased testicular size in the test group...," a tendency toward lower hemoglobin and hematocrit in all rabbits in the test group, "some effect of PMS fluid on sperm maturation...," and testicular atrophy in the test rabbits.

CITE: T 2302 - 2341, Exhibit to K. Olson Deposition, and Exhibit to LeVier Deposition.

Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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