PLAINTIFFS' TRIAL EXHIBIT LIST ABSTRACTS FOR DOW CORNING

Excerpts From: "DOW DOCUMENTS" WHERE THERES SMOKE THERE'S FIRE"

Document #1

CONCEALING FROM FDA

FRAUD/MISREPRESENTATION

MISCELLANEOUS - RECKLESS/CONSCIENCIOUS DISREGARD

"Internal Audit and Corrective Action Plan" prepared by Dow Corning of its

Toxicology Laboratory. The audit uncovered four studies in which a former

Dow Corning employee (Mark Bejarano) created false data and violated Good

Laboratory Practices (GLP). The studies which were falsified are a lifetime

breast implant gel study in rats, a bio-durability study of elastomer in

orthopedic devices, a breast implant elastomer study.

The falsification involved the technician, Bejarano. who created multiple

slides from a single animal and labeled them as though they had come from

different animals. The report states, "It has been acknowledged by Mr.

Bejarano that he: did create multiple slides, made a mistake, acted on his

own, acted contrary to his Dow Corning training, and did not tell his

supervisor or anyone else what he had done." (p.4 or Temporary Dow Corning

Bates Number 411) Dow Corning claims that none of the four studies were

published or relied on for data on the safety of breast implants, that an

outside audit will also be done, and that Dow Corning will examine its

operating procedures for the toxicology laboratory to make sure it complies

with applicable regulatory requirements.

Appendix A is a list of studies in Dow Corning's PMAA master file and a

list of studies in Dow Corning Corporation's blue book. Appendix B is a

list of studies containing duplicate slides created by Mark Bejarano.

Appendix C is qualifications of the consultant.

CITE: DCC 411000406 - 411000525, Exhibit 25 to Zimmer Deposition; Exhibit 4

to Bejarano Deposition; Exhibit 5 to Bey Deposition; Exhibit 35 to McKennon

Deposition. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #2

ACKNOWLEDGEMENT OF NEED FOR TESTING

TESTING

Research Project Description titled "Organosilicone Anticholesterol Agents"

The intent of this experiment is to isolate organosilicon compounds capable

of lowering total serum cholesterol in several species and of ameliorating

atheromata in rabbits. Data collected coincidental to other experiments

have indicated a number of organosilicon compounds that can lower serum

cholesterol, triglycerides, and/or phospholipids in normally fed mice and

rats. Dimethylpolysiloxanes can ameliorate atheromata in rabbits.

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

Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #3

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #4

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 may dependent more upon their chemical, rather than

their physical properties. (p.1)

The proposal notes that Dow Corning has acquired information that certain

silicones are biologically active and has instituted a Biomedical Research

Laboratory in July 1965 "to probe the potential utility of such silicon

chemicals across the broad disciplines of biology, i.e., plant sciences,

microbiology and animal science." (p. 2) Dow Corning Does have the

capability to conduct research on silicons in the pharmaceutical areas

while Lepetit "has been engaged

in s specific endocrine cooperative research program with DC for a period

of two years." (p. 3) The proposal states that the parties would cooperate

to develop new silicon chemicals as drugs including silicones with activity

as androgen depression, central nervous system depression, antimicrobial

activity, etc. (pp. 3-4). Additionally, Dow Corning and Lepetit personnel

will exchange research and information and will travel to the other's

facilities.

CITE: DCC 2801011379 - 281010391, Exhibit to Bennett Deposition (also used

as Exhibit 65 by Dow Corning), Exhibit to Blocksma Deposition (used by Dow

Corning), Exhibit to Isquith Deposition, Exhibit to LeBeau Deposition,

Exhibit to Petraitis Deposition, Exhibit to Rowe Deposition, Exhibit 17 to

Popoff Deposition, Exhibit to Julius Johnson Deposition, and Exhibit to MDL

LeVier Deposition. WITNESS: Bennett (Authenticated in Bennett, Vol. II, p.

455-457). DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare. Dow

Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #5

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #6

ACKNOWLEDGEMENT OF NEED FOR TESTING

TESTING

Research Project Description titled "Antiparkinsonism Activity of 2,6-cis-

and 2,6-trans-(PHMESIO)2(ME2SIO)2)." The objective is to evaluate

PhMeSiO)2(Me2SiO)2) as an antiparkinsonism agent. It has been shown that

these compounds increase whole brain dopamine within 5 days of daily oral

administration.

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

LeVier Deposition. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #7

COHESIVENESS - LIQUID COMPONENT OF GEL

MISCELLANEOUS - COMPLICATIONS

TESTING

Report titled "Discussion of Toxicology of Various Dow Corning Products."

Topics include gel bleed, silicone transport across the skin, the need for

further testing. Dr. Carson recommended that all possible evidence of

adverse effects be collected with supporting data of literature on our part

to show that Dow Corning has no part in these. The presence of Low

Molecular Weight in 350 cs. is the same as in lower cs.

CITE: DCC 281041877 - 281041882. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #8

KNOWLEDGE OF SYSTEMIC DISEASE

MISCELLANEOUS

TESTING

Handwritten synopsis by Lake titled "Status of Biological Testing of

Sila-admantoner Compounds, Dow Corning Report 4234" of research projects

and patent activity. It includes notes regarding fibroblasts and

immunopotentiation, antigen modification, and joint research on in vitro

carcinogen bioassay.

CITE: LAK 133, Exhibit to Radonovich Deposition, Exhibit to Boley

Deposition, and Exhibit to Lake Deposition.

Document #9

TESTING

TISSUE REACTION

Dow Corning document: "I. Silicone Oils as Miticides (or mite-repellents)";

"II. Aphid Control with Silicone Emulsions"; "III. Effect Of Silicone

Emulsions On Mealy Bugs"; and "IV. Effects Of Silicone Oils on

Cockroaches." The document was authored by "JWR" (unknown who this is).

"Mites do not willingly invade silicone treated bean plants if untreated

ones are available." (DCC 16001144). Mites are not controlled by

silicone-treated cucumber plants, possibly because the silicone oil is

absorbed into the plant. A silicone spray was "completely effective in

discouraging them. It is possible that a minor component, relatively

volatile, may be acting as a contact insecticide." (Id.)

Wild mustard plants sprayed with DC 200 fluid 10 cs. eliminated aphids.

"The impression gained is that the insecticidal (or repellent) activity is

due to some component of the fluid which has gone (presumably by

evaporation or by becoming chemically bound within the plant) or a

hydroxy-ended material. It seems worthwhile attempting to identify the

active species and trying to modify it chemically to obtain a long-term

effect." (DCC 61001145).

Pachysandra plants, infested with mealy bugs, were sprayed with an

antitranspirant emulsion with 5% silicone. After 5 days, all mealy bugs on

the treated plants were eliminated. "The silicone appears to be slower

acting here than upon other insects; possibly a repellent, rather than an

insecticidal, effect is involved." (DCC 61001146).

In the 1950s, Texaco and Shell did studies on hydrocarbon oils as insect

attractants. In 1968, it was found by Gorzinski (of Dow Corning) that DC

360 fluid appeared to have an insect attractant and insecticidal activity.

Cockroaches were attracted to the petri dish with silicone fluid. After

coming out of the fluid, they "never got more than a few inches from the

dish before dying." These results indicate "some type of activity existed

in the DC 360 fluid...." (DCC 61001147).

CITE: DCC 16001144 - 16001147, Exhibit to Bennett Deposition, Exhibit 11 to

McKennon Deposition, Exhibit 8 to Harris County Gehring Deposition, Exhibit

to Harris County and MDL LeVier Depositions, Exhibit to Ryan Deposition,

and Exhibit to Isquith Deposition. WITNESS: Bennett (Authenticated in

Bennett, Vol. IV, p. 880;15 - 882:8). DISPOSITION: Admitted in Toole (II)

v. Baxter Healthcare. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #10

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #11

MISCELLANEOUS

Table of 2,6-cis levels in selected products which was attached to LeVier's

memo (see document # 10 above). MDX-4-4514 (elastomer), shunts, penile

implants, chin implants, and other products all contained 2,6-cis.

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

Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #12

VIDEOTAPE PRODUCED AT ZIMMER DEPOSITION ON D4.

CITE: No Bates Number, Exhibit to Zimmer Deposition. Dow Corning Trial

Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #13

10/08/92

COHESIVENESS - LIQUID COMPONENT OF GEL

MISCELLANEOUS

TESTING

"Catalog and Review of D4 Studies." This is a list of all studies by Dow

Corning on D4. There is a handwritten note at the top that says: "Meeting

Oct. 16, 1992, Stark/Bey/Zimmer."

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

Corning Trial Exhibit List Abstracts

PENDLTON/PSC Attorney Work Product/Privileged & Confidential

Document #14

MISCELLANEOUS - ORGANIZATIONAL SURVEY

MISCELLANEOUS - LOBBYING

List of "Desired Product Champion Features" includes that the relationship

with the product champion should fit the Dow Corning Silicone Group

Business Strategy. "PC (product champion) needs to understand and buy-in to

the Silicones Group Business Strategy." Listed features include that the PC

serve as a substantive resource to Dow Corning, be loyal to the company,

have positive peer influence, be politically astute, and demonstrate

teamwork with Dow Corning. The document lists the names of product

champions in the United States and Europe and includes a manual prepared by

Lois Duel dated September 1, 1989 which addresses issues such as the

desired product champion features, the role of the product champion,

product champion management and specific product champion issues.

CITE: KKA 210877 - 210886 Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #15

KNOWLEDGE OF LIQUID SILICONE DANGERS

MISCELLANEOUS

MISCELLANEOUS - COMPLICATIONS

TESTING

Confidential report entitled "Chronology of Silicone Injection." The report

provides a historical account from Dow Corning's perspective of the use of

liquid silicone injections and the establishment of the Center for Aid to

Medical Research. It notes that Dow Corning 200 fluid was used for

industrial applications. When the Medical Products Division was established

in the early 1960's, the 200 fluid was designated Dow Corning 360 Medical

Fluid. The report notes that, "The original label on the new product

carried the inscription 'formerly Dow Corning 200 Fluid.'" (DCC 267371450)

The report also discussed the indictments against Dow Corning officials for

distributing the drug, 360 fluid, and the pleas of no contest which were

eventually entered.

CITE DCC 267371444 - 267371466. NOTE: The document also has Bates numbers

QDC 124506 - 124528 on it as well as Bates numbers MM 369861 - 3698883. Dow

Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #16

ACKNOWLEDGEMENT OF NEED FOR TESTING

SILICA

TESTING

TISSUE REACTION

W.D. Galloway reports on the "Analysis of Lifetime Carcinogenicity Study of

Silicone Gels" conducted by Dow Corning under GLP regulations using

Sprague-Dawley rats injected with Q7-2159A and MDF-0193 gels.

Galloway states:

"Both of the gel-implanted groups showed a large number of cancers compared

to the control group. Particularly striking was the number of sarcomas

(principally fibrosarcomas) which occurred in the treated groups."

"The only obvious deficiency is that only one dose level was used.

Ordinarily, three doses are used, and five are preferred. Based on the

results obtained, I have little doubt that NTP would classify these

substances as likely animal carcinogens."

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

called foreign body tumors."

"Absent epidemiologic data, and without waiting for results of additional

lifetime studies, knowledge of the mechanism by which these tumors was

induced is critical to estimating human risks. It is possible that the

tumors were chemically induced, rather than being induced by a by a

physical mechanism, as Dow suggests. If this is the case, then the argument

that such tumors do not occur in man is untenable. If the tumors were

chemically induced, the active agent is more likely to be one of the

several chemicals which make up the gel, rather than a metabolically

produced reactive intermediate, since the tumors which did occur did not

occur selectively in metabolically active organs such as the liver."

"Recent studies have shown that siloxanes may act as estrogen-like

substances and can enhance the growth of tumor cells."

CITE: M 780064 - 780065. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #17

COHESIVENESS - LIQUID COMPONENT OF GEL

KNOWLEDGE OF GEL BLEED

MISCELLANEOUS

SILICA

Dow Corning materials identification list for final devices. It lists all

materials used in final devices with a Dow Corning code number. The two

manufacturing sites, Michigan and Tennessee, use different identification

codes. The list also gives material formulations, indicates the need for a

low-bleed outer shell liner, identifies whether "responsive" gel or "firm"

gel is used, and notes the percentage of silica used in the formulations.

CITE: KMM 447209 - 4477224 Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #18

Post 10/92

COHESIVENESS - LIQUID COMPONENT OF GEL

KNOWLEDGE OF GEL BLEED

MISCELLANEOUS - COMPLICATIONS

RUPTURE

SHELL STRENGTH - THICKNESS

Dr. O. Gordon Robinson Presents a paper entitled "Rate of Rupture of

Silicone Prostheses: Excerpt From A Study Of Over #3000 Personal Cases and

Twenty-Five Years Experience" at the Symposium on Reoperative Aesthetic

Surgery of the Face and Breast in Naples. Florida. Robinson discusses

results obtained after 115 patients were followed after the fall of 1990

after receiving breast implants. Of the 115 patients, 57% had rupture of

one or both implants. An additional 20% had moderate to severe bleed on one

or both sides. The patients had the implants from six months to 25 years.

Dr. Robinson concludes that all gel and bi-lumen implants:

"should be replaced at about the eighth post-operative year because it can

be fairly well predicted that at this stage the prostheses in most cases

would still be intact and much easier to replace. If a period of time

longer than twelve to fourteen years is allowed to elapse, then the

prostheses have a good chance of being ruptured and the exchange would be

much more difficult.

CITE: PSC Medical Articles CD, J 2698 - Exhibit 2 to Robinson Deposition,

Exhibit 25 to McKennon Deposition. WITNESS: Robinson. DISPOSITION: Not

admitted in Toole (II) v. Baxter Healthcare Dow Corning Trial Exhibit List

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #19

Post/10/92

KNOWLLEDGE OF GEL BLEED

MISCELLANEOUS - COMPLICATIONS

RUPTURE

SHELL DEGRADATION

SHELL STRENGTH - THICKNESS

Dr. O. Gordon Robinson's abstract of a paper entitled "Disruption Rate Of

Silicone Gel Prostheses - A Report Of 200 Cases." 200 patients from 02/91 -

10/92 had their silicone gel implants removed. The time from implantation

ranged from six months to 25 years. Robinson found that 104 or 52% had one

or both implants ruptured, 43 or 21.5% had severe bleed, and 147 or 73.5%

had "distortion" - rupture plus severe bleed. Based on this data, Robinson

projected future rupture rates using the Kaplan-Meier survival curve, and

concluded that in 20 years, only 3.4% of the patients will have both

prostheses still intact. He states, "Gel filled mammary prostheses wear out

and in a certain predictable time frame. Based on this study, patients can

be advised with a certain degree of accuracy as to the probable condition

of their prostheses."

CITE: No Bates Number, Exhibit 3 to Robinson Deposition. WITNESS: Robinson

DISPOSITION: Not admitted in Toole (II) v. Baxter Healthcare.

Document #20

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #21

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #22

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #23 through#31

#23

ANY FOLLOW-UP STUDIES BY DR. O. GORDON ROBINSON.

This includes an abstract by Dr. Robinson and Dr. Edwin Bradley entitled

"Disruption Rate of Silicone Gel Prostheses - A Report of 200 Cases"

published in the January 1995 issue of the American Medical Association

Journal.

#24

PHOTOGRAPHS OF PLAINTIFF'S EXPLANT SURGERY

#25

EXPLANTED IMPLANTS OF PLAINTIFF AND PHOTOGRAPHS THEREOF.

#26

MEDICAL RECORDS OF PLAINTIFF.

#27

MEDICAL BILLS OF PLAINTIFF.

#28

PATHOLOGY SLIDES AND TISSUE SAMPLES OF PLAINTIFF.

#29

SPECIMEN BREAST IMPLANTS.

#30

SELECTED COMPLAINT REPORTS, FORMS AND/OR RESPONSES.

#31

ALL PRODUCT DATA SHEETS OF DOW CORNING FOR MAMMARY PROSTHESES. Dow Corning

Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #32

09/14/54

SILICA

KNOWLEDGE OF SYSTEMIC DESEASE

H.C. Spencer, Dow Chemical, note regarding "Dow Corning Hydrophobic

Silica." Testing shows a "high order of toxicity from dust inhalation."

CITE: TDC 5488. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #33

03/28/55

MISCELLANEOUS - COMPLICATIONS

SILICA

TISSUE REACTION

"Report Of Trip To Saranac Lake Laboratories" by V.K. Rowe of Dow Chemical

prepared for Dow Corning. Rowe and other Dow Chemical scientists visited

Saranac Laboratory to verify work they had done on D.C. Degusa silica for

Dow Corning. Rowe, et al. reviewed the work and wrote this report on the

conclusions of the tests.

Dow Corning silica consists of crystalline silica. Rowe states that, D.C.

Degusa (silica) dust is "capable of causing diffuse cellular infiltration

and fibrotic changes in the lungs and other organs of certain types of

animals. It also produces bronchitis and sometimes emphysema." However, he

concludes that it is not likely to cause silicosis" in the ordinary sense

of the word. If fibrotic changes of the lungs develop in man, they will

probably be diffuse in character. If exposure is stopped, a measure of

recovery is quite possible. Exposure to crystalline free silica reactivates

and aggravates tuberculosis & causes progressive lesions." (DCC 299000444).

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

to California Braley Deposition. Dow Corning Trial Exhibit List Abstracts

PENDLETO/PSC Attorney Work Product/Privileged & Confidential

Document #34

01/00/56

TESTING

KNOWLEDGE OF LIQUID SILICONE DANGERS

GEL MIGRATION

Dow Corning Report No. 1377 on "The Physiological Assimilation Of DC 200

Fluid" by M.B. Chenoweth (Dow Chemical), R. Holmes and F. Stark. A copy was

distributed to Collings, Bass, Kauppi, Hunter, Hutchison, Hyde, Blackburn,

Bennett, McHard, CRI, and others including Beamer of Dow Chemical. "An

increasing use of siloxanes for medicinal applications has resulted in the

need for information on their biological activity. Previous experiments of

The Dow Chemical Company Biochemical Department has shown that many of

these compounds were toxicologically inert. It was the purpose of this

experiment to determine to what extent the polydimethylsiloxanes were

assimilated, and if so were they were metabolized." (I 169). C14 labeled

PDMS in antifoam emulsion was administered to 2 albino rats and 2 lactating

dogs. "The preoperative care, administering of the labeled fluid,

sacrificing and dissecting of the animals was carried on by Dr. M.B.

Chenoweth of The Dow Chemical Biochemistry Department. Samples of tissue

were analyzed with the cooperation of Dow's Radiochemistry Laboratory." (I

171). With intramuscular injection, the C14 siloxane was found in the

intestines, right adrenal, skin and hair, heart, skull bone, brain, kidney,

urine, liver, muscle, lung, renal fat, blood and spleen. (I 172). Rats fed

with the material had siloxane in the ileum, stomach and content, bladder

and urine and kidney. (I 174). "The actual amount present may be greater by

a factor of 3 corresponding to total polydimethylsiloxane from Dow Corning

200 Fluid and from gum. It is unlikely that the polydimethylsiloxane in the

gum would be more readily assimilated than the lower molecular weight 200

Fluid." (I 174). A lactating dog fed with the material has siloxane in the

skin and hair, brain, bile,, liver, kidney, heart, milk, urine, skeletal

muscle, lung, adrenal, and blood. (I 175). A second lactating dog also had

siloxane in the bile, skin and hair, adrenal, urine, spleen, lung, heart,

liver, thyroid, pancreas, blood from lung, skeletal muscle, and milk. (I 175).

"The studies conducted along these lines (C14 labeled fluid) to date have

shown that these compounds are absorbed from the gastro-intestinal tracts

to a slight extent, the amount absorbed being of the order of .0001%.

Toxicological studies have shown these compounds to be inert." (I 175).

There is a cite to the lab notebooks for the studies. On 259803.

CITE: KMM 259794 - 259803, Exhibit to Harris County LeVier Deposition,

Exhibit to Tyler Deposition, Exhibit 20 to Harris County Zahalsky

Deposition. DUPLICATE: I 167 - 176. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #35

02/09/56

KNOWLEDGE OF LIQUID SILICONE DANGERS

MISCELLANEOUS

MISCELLANEOUS - COMPLICATIONS

TESTING

McGregor, Dow Corning, memo to Rowe, Dow Chemical Biochemical Research,

enclosing 9 samples of silicone fluids for determination of the effect of

intravenous injection. McGregor wants to know if any of the silicone fluids

can be tolerated when injected intravenously. The silicone samples include

200 fluid, 555 fluid, 710 fluid, antifoam AF emulsion (which contains 30%

200 fluid), and XEC-5027 (which contains 10% 200 fluid).

CITE: OOT 43674 - 43700, Exhibit to K. Olson Deposition, Exhibit to Rowe

Deposition, Exhibit 24 to Harris County Rowe Deposition. and Exhibit to

McHard Deposition. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #36

08/00/57

KNOWLEDGE OF LIQUID SILICONE DANGERS

MISCELLANEOUS

MISCELLANEOUS - COMPLICATIONS

TESTING

TISSUE REACTION

Study by Stark titled " The Physiological Activity Of Dow Corning 200

Fluid." By a mechanism unknown at this time, a small amount of Dow Corning

200 Fluid is absorbed through the skin by the adrenal and kidneys of a rabbit.

CITE: KMM 259804 - 295808. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #37

10/05/57

COHESIVENESS - LIQUID COMPONENT OF GEL

MISCELLANEOUS - COMPLICATIONS

TESTING

TISSUE REACTION

Dow Corning's version of a "Report Prepared for Dow Corning Corporation,

Midland, Michigan on Five Silicone Materials." The original report (see

document #38 below) was prepared by Dr. W. Deichmann of the University of

Miami on October 5, 1957 but was a report on six silicone materials. This

version of Dr. Deichmann’s report was altered to delete one compound

and to delete all adverse effects identified in Dr. Deichmann's original

report.

In this version, five Dow Corning silicones were fed to albino male and

female rats for a period of 90 days. The silicones were Dow Corning 200

Fluid (50, 350, 1000, 10000 and 60000 cs.). Based on the observations of

body weight, food intake, hematology, organ weight at necropsy, and their

gross and microscopic appearance, it was concluded that none of the Dow

Corning 200 Fluids of the viscosity range fed caused any harmful or

deleterious effects.

CITE: KKM 7896 - 7930. NOTE: Includes a summary of animal safety studies

relating to dimethylpolysiloxane fluid. See document #38 for the original,

unaltered version of Dr. Deichmann's report produced by Dow Chemical. This

altered version of the report was produced by Dow Corning. Dow Corning

Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #38

10/05/57

COHESIVENESS - LIQUID COMPONENT OF GEL

MISCELLANEOUS - COMPLICATIONS

TESTING

TISSUE REACTION

Dr. W. Deichmann's original "Report Prepared for the Dow Corning

Corporation, Midland Michigan on Six Silicone Materials" Six Dow Corning

silicones were fed to albino male and female rats for a period of 90 days.

The silicones were Dow Corning 200 Fluid (50, 250, 1,000, 10,000, and

60,000 cs.) and Dow Corning Z-4141 Solvent Free (the latter compound is the

compound deleted by Dow Corning is document #37 above).

 

ORIGINAL REPORT

DOW CORNING ALTERED REPORT

2 rats died during experiment

There was an apparent decrease in the number of leukocytes. This difference

is considered statistically significant. It is apparent there is a

depression in the output of granulocytes by the bone marrow.

1 rat died

There was an apparent decrease in the number of leukocytes. This is not

statistically significant. The dietary feeding of DC 200 fluids had no

significant effect upon the leukocyte counts of the treated animals.

  The livers of the rat fed Z-4141 were significantly greater than the

controls. This is consistent with the observation of liver damage in these

animals.

None of the organ weights differed from the controls 

The feeding of the six compounds depressed the granulocytic elements of

the peripheral tail blood of female rats. The livers of the rats fed Z-4141

were significantly heavier than the livers of the controls and also

demonstrated fatty infiltration or degeneration.

The feeding of the five compounds had no harmful or deleterious effects

CITE: TDC 6079 - 6100. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #39

10/09/57

COHESIVENESS - LIQUID COMPONENT OF GEL

MISCELLANEOUS - COMPLICATIONS

TESTING

TISSUE REACTION

Dr. Deichmann, University of Miami, writes to McGregor, Dow Corning,

enclosing the results of the review of the six Dow Corning silicone

compounds. He informs McGregor that all six compounds depressed the

granulocytic elements of the peripheral (tail) blood of the female rats,

and that the livers of rats fed Z-4141 were significantly heavier than the

controls and demonstrated fatty infiltration or degeneration.

CITE: M 420103. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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 anti-fungal 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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #43

07/05/62

KNOWLEDGE OF LIQUID SILICONE DANGERS

MISCELLANEOUS - COMPLICATIONS

TESTING

TISSUE REACTION

Olson and Sadek, Dow Chemical Biochemical Research, letter to McHard, Dow

Corning, on toxicity by subcutaneous injection of Dow Corning 200 Fluids

and Dow Corning 555 And 550 Fluids. Dow Corning 200 fluid 10 cs. resulted

in a moderate inflammatory response in the subcutis as indicated by the

presence of polymorphonuclear cells and a very large mononuclear cells.

"This type of inflammatory reactions is interpreted as due to infection."

With DC 555 and 550 Fluid, all injection sites showed evidence of

inflammatory reaction indicated by the presence by mononuclear cells and

polymorphonnuclear cells.

CITE: TDC 7493 - 7515, Exhibit 9 to Hancock Deposition, Exhibit to McHard

Deposition, and Exhibit to K. Olson Deposition. Dow Corning Trial Exhibit

List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #44

07/12/62

SHELL STRENGTH - THICKNESS

S. Braley, Dow Corning, reports on a telephone call with Dr. Gerow

regarding his findings from the use of the saline silastic prosthesis. A

leak was discovered during implantation and Dr. Gerow "sealed it with

cement on the operating table...." Also, he wanted Dow Corning to "make the

Gel gooier." Dr. Gerow reports that the saline he has been using in some of

the silastic sacs has been in animals for nine months and that the body

sets up a chemical balance. He has analyzed the fluid inside the sacs after

this nine months and found protein, SO4 ions and also indications that the

body had set up a balance of magnesium and other ions. Finally, Dr. Gerow

stated that the "direct injection technique has worked out beautifully."

CITE: M 320001 - 320002. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #45

09/14/62

TESTING

Dow Chemical Texas Division, Agricultural Research, study by F.C. Turner,

K.G. Seymour, and J.B. Jackson on "Tropical Application Of Various Solvents

And Solutions To Evaluate Dermal Irritation." Report No. 210. The report

was circulated many persons including K.W. McCory of Dow International;

persons at Bioproducts: Adm., J.E. Johnson; An.Sci. R and D, T.A. Hymas;

Plt.Sci. R and D, K.C. Barrons; Midland BRC Files, L.J. Lippie:

Registration Section. G.E. Lynn; Synthesis Group, W. Reifschneider; and

Formulation Res., J.W. VanValkenburg; to V.K. Rowe of Biochemical Research;

and to the following persons at Pitman-Moore: C.W. Hinman, G.R. Burch, and

D.C. Brinkman.

Dow Corning 200 fluid - silicone oil with 49% espesol 5 content was

administered in 10 cc dosages to shaved strips on the hide to test for

suitable solvents for Ruelene. Dow Chemical hoped to find a solvent that

didn't damage the hides of cattle when Ruelene was administered. The DC 200

fluid was rated ad bad, which indicated that the hide had extreme cracking

or sloughing at 10 and 16 days after application. (TDC 7542).

CITE: TDC 7537 - 7543. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #46

10/04/62

ACKNOWLEDGEMENT OF NEED FOR TESTING

COHESIVENESS - LIQUID COMPONENT OF GEL

KNOWLEDGE OF GEL BLEED

KNOWLEDGE OF LIQUID SILICONE DANGERS

SHELL STRENGTH - THICKNESS

TISSUE REACTION

S.Braley, Dow Corning, memo regarding telephone call to Dr. Thomas D.

Cronin. Braley told Cronin that the uncatalyzed breast material could not

be sent out because there were too many problems with it. The problems with

measuring and the variability of both the base material and the mixing

techniques necessitates different amounts of cross-link resulting, along

with the variability in mixing techniques, can cause difficulties.

Dr. Frank Gerow was also on the telephone and talked about the results he

was getting regarding tissue reaction to the direct injection of the material.

Cronin said that he is not concerned about leakage if he were to use the

thin material because a film forms around the implant retaining the

material in place. Cronin said that he is getting chlorine, potassium and

proteins both in and out through the wall of the bag. This is on apparently

good bags.

It was decided that it would be wise to continue the work for long range

testing for the acceptability of the material.

CITE: OOM 320665 - 320666. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #47

10/31/63

KNOWLEDGE OF LIQUID SILICON DANGERS

GEL MIGRATION

Dr. Walter Berman writes to Silas Braley, Dow corning, reporting on his

injection of silicone fluid in mice. Two days after injection, silicone was

found in most organs including the brain, liver, spleen, intestinal wall,

adrenal and kidney. He also found "evidence of at least radio activity and

most probably silicone in the brain and all of the various other organs...."

CITE: M 420051 - 420052. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #48

11/27/63

TESTING

TISSUE REACTION

Dow Chemical's Bioproducts Department report by Whitney, Pollock and Pauley

on "Fluorosilanes As Fumigants." Six flourosilanes:K-56,425 =

n-propyltrifluorosilane; K-56,426 = ethylmethyldifluorosilane; K-57,317=

trimethylfluorosilane; K-59,489 = mehtyltrifluorosilane; K-59,697

=chlorometthyldifluoromethylsilane; K-58,739 = silicon tetrafluoride;

andK-681 = methyl bromide were evaluated as fumigants for control of

insects and microorganisms. All were very active against post-embryonic

stages of tests insects. Tri and difluoro silanes were active against

bacteria and molds. Most of the compounds killed all flour beetle eggs at

one lb/1000 cu. ft. with a 16-hour exposure.... A patent disclosure has

been submitted and further research is recommended for these and related

compounds.

Results of toxicological work with mammals is reported in reports

55.11-56425-1, 55.11-56426-1, 55.11-56427-1, 55.11-57317-1, and 55.11-2-1.

the usefulness of these compounds has been reported in Patent Disclosure

no. 16193. NOTE: None of these reports or patent disclosures were produced

to the PSC.

"Further exploration of the biological and physical properties of these and

related compounds is recommended."

CITE: TDC 8901- 8904. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #49

00/00/64

MISCELLANEOUS - COMPLICATIONS

SILICA STERILIZATION/CONTAMINATION

TISSUE REACTION

Braley, Dow Corning, states in the Trans American Society of Artificial

Internal Organs, "The Medical Silicones," that electrical charges exist on

the surface of the silicone elastomer. Silicone elastomers are described as

non-adherence products, nothing will stick to them. "However, because of

the dialectic (sic) properties of silicone rubber, it will develop a

surface charge and can hold dust, lint, (etc.).... This is not true

adhesion." Additionally, the reason that the attempt to create a silicone

vascular prostheses, to be inserted in a blood vessel, failed is because of

the electrical charges on the surface which caused the blood to clot at the

ingress end of the silicone prostheses tube.

Braley also describes the chemical composition, the characteristics and the

various applications of silicone. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #52

05/28/64

FRAUD/MISREPRESENTATION

GEL MIGRATION

MISCELLANEOUS - COMPLICATIONS

TISSUE REACTION

Braley memo to Ashley, Blocksma, R. Dingman, Edgerton, Goulian, Lederer,

Murray, Rees, Badamo, Bass, H. Dingman, Haberstroh, Hodnett, Honter,

McHard, Mullison, Rhodes, and Stebleton regarding the attached article in

the May 25, 1964 issue of "The Insider"s Newsletter." Unknown factors with

silicone injections include absorption, migration and hardening.. Braley

writes, "We have no knowledge where the reporter obtained this information.

If anyone knows anything about this, we'd appreciate hearing from him. We

are trying to keep such articles as this out of the public eye as much as

possible."

CITE: M 350063 - 350064. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & confidential

Document #53

09/22/64

KNOWLEDGE OF LIQUID SILICONE DANGERS

GEL MIGRATION

Thomas Rees letter to Braley, Dow Corning, regarding the finding of altered

fat cells in animals sub-cutaneously injected with silicone. Rees states

that the spleens of the mice that have been injected with massive amounts

of the material show definite collection of silicone within macrophages.

CITE: KMM 167416. Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC

Attorney Work Product/Privileged & Confidential

Document #54

09/24/64

TISSUE REACTION

SHELL DEGRADATION

SHELL STRENGTH - THICKNESS

Letter from Dr. Thomas Cronin to William Rhodes, General Manager of Dow

Corning. Dr. Cronin reports that Dr. Brauer had to remove seven implants

when, at intervals of 2-4 months, a blister would start in the scar and

gradually break down. "(S)ome clear, straw colored fluid would be released"

CITE: KMM 150269 - 150270. NOTE: Ivory flakes were being used to prepare

the implants prior to surgery. Dow Corning Trial Exhibit List

Abstracts/PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #55

11/12/64

EMBOLISM

KNOWLEDGE OF LIQUID SILICONE DANGERS

Harry Dingman, Dow Corning's Legal Counsel, writes to Ban Smart of the FDA

and informs him of a reported fatality following injection of a silicone.

Dr. Crenshaw, California, injected a woman with silicone (source and type

unknown) mixed with a vegetable oil. she "then went into a coma in a matter

of a few hours, and died within a few days. Dr. Aronow had not received a

formal coroner's report, but the informal comment was to the effect that

death was due to fat emboli in the lung and possibly in the liver. A

suspicion of possible encephalitis was being checked by having a culture

run on the brain." (emphasis added).

CITE: KKM 1275 - 1276. DUPLICATE: KMM 48637 - 48638. Dow Corning Trial

Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #56

12/00/64

KNOWLEDGE OF LIQUID SILICONE DANGERS

MISCELLANEOUS - COMPLICATIONS

TISSUE REACTION

"Tissue Reactions to Injected Silicone Liquids, A Report of Three Cases,"

Archives of Dermatology, Vol. 90, 538-593 by Winer, Sternberg, Lehman and

Ashley. Drs. Oppenheimer and Russell observed fibrosarcomas developing in

1.7% to 40% of the test animals. Drs. Hur and Neuman observed malignant

epithelial tumors that were believed to be of sweat gland origin. The

conclusion drawn from the test data is that "there seems to be sufficient

evidence at this time that complications of this nature are to be expected."

CITE: I 253 - 259, Exhibit 7 to McGhan Deposition, and Exhibit 16 to

California Braley Deposition. DUPLICATE: PSC Medical Articles CD, J 3598 -

3603. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #57

12/08/64

KNOWLEDGE OF LIQUID SILICONE DANGERS

TISSUE REACTION

Dr. Franklin Ashley writes to Silas Braley, Dow Corning, regarding a "girl

in Las Vegas who received the injections and had the eye trouble." The 28

year old woman received 30 injections into the breast.

Ten to fifteen minutes following her final injection she noted onset of

nausea followed by dizziness and almost complete loss of vision. At the

same time she developed severe left anterior chest pains without dyspnea or

tachypnea.

She was seen by an Internist who treated her with ACTH thinking that this

possibly represented an anaphylactoid reaction. Visual disturbance cleared

somewhat with ACTH. During this immediate post treatment period she

experienced some loss of memory, as well as poor coordination which cleared

gradually over a period of time. Also noted during this time was hematuria

which lasted for one day only; no recurrence has been noted.

One week following the onset of symptoms she was evaluated by Dr. Albouth,

at which time he noted a questionable positive Rhomberg and ophthalmologic

findings consisting of some loss of visual acuity and hemorrhages within

and anterior to the retina.

Follow-up to date has been over a six month period with the latest notation

that her gait has returned to normal. Her dizziness has disappeared, but

she still experiences some visual difficulties, specifically loss of visual

acuity. (emphasis added).

CITE KKH 63126 - 63127. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #58

01/29/65

KNOWLEDGE OF LIQUID SILICONE DANGERS

Franklin Ashley, UCLA Center for the Health Sciences, to Braley, Dow

Corning, reporting the death of a patient after various injections of

silicone around the face. (emphasis added).

CITE: M 340057. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #59

04/01/65

CONCEALING FROM FDA

KNOWLEDGE OF LIQUID SILICONE DANGERS

Dr. Franklin Ashley responds to Silas Braley's, Dow Corning, letter

concerning a girl in Argentina who was injected with large amounts of

silicone fluid. "I believe this would fit in also with the observations of

Goulian and others where a large quantity was injected any one time, and

was taken up by the lymphatics. We have not observed this in any of our

cases, however, probably due to the fact that we inject only a small

quantity each time.... I do not think this should be reported to the FDA as

it is an isolated case and from another country, and we do not know exactly

what they injected really." (emphasis added).

CITE: M 340044. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #60

05/27/65

EMBOLISM

KNOWLEDGE OF LIQUID SILICONE DANGERS

Frank Ashley, M.D., reports to Silas Braley of Dow Corning regarding a

consultation with a patient in Las Vegas. Ashley states, "My diagnosis, of

course, was multiple silicone emboli from the liquid silicone and possible

additives, in the lungs, brain, liver, kidney and retina." (emphasis added).

CITE: M 340037. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #61

06/24/65

KNOWLEDGE OF LIQUID SILICONE DANGERS

GEL MIGRATION

Dr. T. Rees writes a letter to Dr. Silas Braley and Fred Dennett, Dow

Corning Center for Aid to Medical Research. Dr. Rees states "The inevitable

has happened. We found a case of carcinoma of the breast in a 37 year old

woman who has had both breast heavily injected with pure silicone

material." He states'

"The carcinoma itself was a very small, isolated, intraductal type of

carcinoma in the upper portion of the tail of the breast and there were

some involved lymph nodes in the axilla. There are multiple 'silicone

cysts' throughout the tissue and some of the silicone was injected in the

immediate vicinity of the carcinoma. Also of considerable interest is that

there is evidence of silicone deposits in the lymph nodes of the axilla and

thus it appears that the silicone is drained to a certain extent by the

lymphatic system..... We are thinking of writing this up as a case report,

but would like the view of the entire committee before we commence doing

so. We are hesitant to report it because undoubtedly it will create quite a

stir but feel that the case must be reported for the sake of thoroughness

and completeness. We are open to counsel as to just what manner this should

be done. (emphasis added).

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

3802 - 3803. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

Document #62

10/05/65

ACKNOWLEDGEMENT OF NEED FOR TESTING

MISCELLANEOUS - COMPLICATIONS

SILICA

TESTING

Hobbs memo to Snedeker with copies to McHard regarding "Recommendations for

the toxicological evaluation of J. Treated Dow Corning Silica Type A." "At

the present time very little is known on the toxicity of the various

treated silicas at Dow Corning.... The exact toxic manifestations are

unknown. They will cause death in laboratory animals by various routes of

administration, including inhalation, for a period of four hours or less.

Although these are high concentrations for a short period of time. we must

assume until proven otherwise that low concentrations over long periods of

time are detrimental to health. It is therefore our recommendation that

acute range-finding studies be performed on J Treated Silica." Testing

programs (such as annual chest x-rays of workers) have been run with the

cooperation of the Dow Medical and Biochemistry Departments on problems

which have arisen with various chemicals. The programs at Dow and Dow

Corning were dropped but, "Recently problems have arisen with chemicals and

compounds which indicate that such a preventative medical testing program

is not only desirable but also advisable.... While toxicity studies are

being carried out on some of these materials at the Dow Biochemistry

Department, they are made with animals, usually on short term acute

exposures. This type of information does not indicate what might happen

over long periods of time subjected to less than acute exposures." The

document also talks about a Medical-Biological-Safety Committee."

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

Olson Deposition. 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

SHELL DEGRADATION

SHELL STRENGTH - THICKNESS

TESTING

TISSUE REACTION

Burdick, Dow Corning, memo to Don McGhan, Weiler, VerVoort, and Pellikka

regarding "Mammary Implants." He states:

"There are still a number of questions concerning our breast units that

have not been answered. We know that a quantity of low molecular weigh

material is exuding from the bag, but that is all.

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

"This test should tell us how the gel is affecting the rubber bag. Adhesion

and tear strength should also be related to swell. The extractables may be

of low enough molecular weigh to migrate throughout the body. If so, what

quantity are we talking about?

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

McGhan Deposition. Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC

Attorney Work Product/Privileged & Confidential

Document #64

11/15/65

EMBOLISM

KNOWLEDGE OF LIQUID SILICONE DANGERS

Dr. Ashley authors a paper, "Silicone Fluid And Soft Tissue Augmentation,

as a result of the Boca Raton symposium. "Of significance is the fact that

the clinical use of silicon liquids in man preceded any responsible and

controlled experiments in animals." As a result of the concern, ASPRS set

up a committee consisting of Dr. Franklin Ashley, Dr. Ralph Blocksma, Dr.

Reed Dingman, Dr. Milton Edgerton, Dr. Dicran Goulian, Jr., Dr. Francis

Lederer, Dr. Joseph Murray, Dr. Norman Orentreich, and Dr. Thomas Rees.

Dr. Ashley provides a historical overview of the chemical properties and

development of silicone. He notes that with intravenous injection of

silicone fluid in animals, large doses are usually fatal in rabbits and can

produce emboli and death in dogs. He found no tissue reaction in animals

when liquid silicone was injected subcutaneously.

Dr. Ashley also notes that silicone oil "will have a tendency to disappear"

within the body and that:

"(S)ignificant questions ... remain unsolved. First, what is the body

distribution within its tissues of any absorbed material? Second, what is

the ultimate fate of the absorbed material? ... Third, if significant

amounts are absorbed, does the body excrete the material, and if so, how,

and how much? Fourth, if some is retained, in which organ or organs is a

harmful effect produced - if any? Indeed, there is some evidence that

silicone oils may be transported to far removed tissues and organs. In

another study, one week after the intramuscular injection of a rat with

dimethyl polysiloxane, 90 per cent of the C(14) labeled liquid oil was

detected within the tissues of the intestinal tract. The fate and presence

of silicone oil in human biology is unknown." (emphasis added). He further

notes that, "In large subcutaneous injections of silicone fluid,

examination of the contents of the abdominal cavity showed that the

mesenteric and omental fat was abnormally firm, with loss of normal color

and adherence to adjacent viscera. This suggests that there may have been

transport of silicone oil through the abdominal cavity." (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. Dow Corning Trial Exhibit

List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit

List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts PENDLETON/PSC

Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstract

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial

Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

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