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(This is a re-typed copy of original Dow Corning Corporation documents. They are not to be reproduced for any reason whatsoever.)
(This is a re-typed copy of original Dow Corning Corporation documents. They are not to be reproduced for any reason whatsoever.)
PRODUCED BY DCC & DCW
INTERIM REPORT
CLIENT: Medical Products Division
Dow Corning Corporation
Midland, Michigan 48140
ATTENTION: Mr. Arthur Rathjen
TITLE: Implantation Study in Rabbits with Four Mammary Gels
INVESTIGATOR: Steven Carson, Ph.D.
EXPERIMENTAL
REFERENCE
NUMBER: A-1544
DATE: March 6, 1975
SUBMITTED BY: Richard E. Kruger, M.Sc.
Research Associate
REK: nb
BIOMETRIC
Biometric Testing Inc. 156 Algonquin Parkway, Whippany, New Jersey 07081
Whippany Laboratory (201) 386-1033
This report is submitted for the exclusive use of the person. . .
A-1544
Dow Corning
Page 2
PRODUCED BY DCC & DCW
INTRODUCTION:
The following herein reports the interim findings of a 90-day gel implantation study in albino rabbits using four (4) test mammary gel preparations. This study was performed at the behest of the Dow Corning Corporation, Midland, Michigan 48640. Samples were received on January 22, 1975, and identified in the following manner:
Sample # Description
A 2 plastic containers each containing
silicone gel: X7-2147; Lot E2457-59, 4.
B 2 plastic containers each containing
silicone gel: X7-2159A; Lot E2457-59, 3.
C 2 plastic containers each containing
silicone gel: X7-2165; Lot E2457-39-1.
D 2 plastic containers each containing
silicone gel: X7-2159A; Lot E2457-59,2.
Methodology:
Twenty-Eight (28) adult, virgin New Zealand white rabbits, weighing between 2.15 and 5.20 kg.. each were utilized in this study. The rabbits were individually housed in temperature and humidity controlled quarters and given a nutritionally adequate rabbit ration and tap water ad-lib. Body weights were recorded weekly, and appetite and elimination were observed daily (Table I).
The rabbits were divided into four (4) test groups containing the following numbers of animals:
Test Group No. of Rabbits
7-day group 4
14-day group 8
21-day group 8
90-day group 8
The four (4) test materials were designated A, B, C and D respectively.
PRODUCED BY DCC & DCW
Each rabbit received all four (4) materials in the following manner: The back of the rabbit was shaved (about 10% of the body surface), and then divided into four (4) quadrants labeled A, B, C and D. The back was then sprayed with Merthiolate. Each test material was then drawn into a sterile plastic syringe using an 18 gauge, sterile needle. The needle was inserted through the skin into the spinus rectal muscle. Approximately 0.3 cc of each material was deposited into each site. Immediately after deposition, the needle was withdrawn slowly to pull the gel back along the needle tract. This procedure caused elongated "blobs" of the gels to form that measured approximately 4 mm to 40 mm.
The implantation sites were rotated as follows:
AB - DA etc.
DC CB
on each animal to ensure a random deposition of the gels throughout all the groups.
The rabbits were returned to their cages. At the end of specific intervals; namely, 7, 14, and 21 days post implantation, 4, 8, and 8 rabbits respectively were sacrificed. Those portions of the spinus rectus muscle containing the test material were removed and fixed in 10% neutral buffered formalin and submitted for histopathologic exam. A complete autopsy was performed, and all tissues and organs were fixed and stored in 10% neutral buffered formalin and saved pending instructions from the sponsor as to their diposition.
RESULTS:
7-day Group:
There were no significant gross pathologic findings on autopsy seen in any of the four (4) rabbits examined. The implantation sites could be differentiated from the rest of the muscle, only by visualizing the "blob" of gel through the fascia. There were no signs of inflammation seen in any of the sites in any of the rabbits of this group. Microscopic exam of the implant site revealed a mile to moderately acute granulomatous inflammatory reaction occurring in all sites. There was no real difference in the severity of tissue response between any of the four (4) test gels.
14-Day Group:
There was one (1) death occurring in this group. Rabbit #2[*] died four (4) days after implantation. Gross findings included pulmonary congestion. G. I. hemorrhaging, and a general atrophy of all major organs. This death was not, in our opinion, attributable to treatment.
There were no significant gross pathological findings for this group. Microscopically, this only noteworthy finding continued to be a localized (mild to moderately acute) granulomatous inflammatory reaction around the periphery of the implantation site. There was no significant difference in tissue response between the four (4) test materials.
21-Day Group:
As with the two previous groups of rabbits, there were no significant gross pathological findings observed at autopsy.
Histopathologic exam reveals the continued presence of a mild to moderately acute granulomatous inflammatory reaction occurring in almost all of the implantation sites. The only difference separating this group from the previous tow is that the reaction in this group of rabbits is lessened slightly. Again, from the results, one cannot discern a significant difference in tissue response between any of the four (4) test gels.
Eight (8) rabbits remain on test until the 90-days sacrifice interval.
Observations are continuing.
SUMMARY:
Twenty-eight (28) adult virgin rabbits were selected for this study and divided into four (4) test groups which gave been and will be sacrificed at specified intervals after implantation of four (4) test mammary gels.
The rabbits received each of the four(4) test gels intramuscularly at a dose of 0.5 cc per site into the spinus rectus muscle.
To date, (3) groups of rabbits have been sacrificed at 7, 14, and 21 days post implantation.
There have been no significant gross pathological finding.
Microscopic exam of the implant sites reveals a localized, mild to moderately acute granulomatous inflammatory reaction. This reaction lessened somewhat in the 21-day animals. Because this response was seen in almost ever implant site and was unequally distributed around the circumference of the site, we feel that this reaction was due to the trauma of implantation and not due to the test gels.
The rabbits exhibited normal appetite, elimination, behavior and weight gain during the respective test periods.
A final group of eight (8) rabbits continues on test, awaiting sacrifice at 90 days.
Detailed pathology readings comparing the various time durations will be included in the final report.[80-DAY FINDINGS]
. . .
RESULTS:
The findings of those rabbits sacrificed at 7, 14, and 21 days were the subject of a previous report (A-1544) dated March 6, 1975.
This report herein reports the finding obtained from those rabbits sacrificed at 80 days post implantation.
At autopsy, no significant pathological findings were observed in any of the rabbits.
Histopathologic exam revealed the presence of mild, subacute granulomatous inflammatory lesions with or without fibroblastic activity. In several of the implantation sites, this response was seen in small portions of the site, with the remainder essentially free of any inflammatory response. In a majority of cases, the reaction was not present in any region of the implant site. There were no significant difference noted a month the four test mammary gels.
It is our opinion that the inflammatory response seen at 7, 14, 21, and 80 days was due solely to the trauma of implantation and no due to any of the four test gels.
SUMMARY:
Twenty-eight (28) adult virgin rabbits were selected for this study and divided into four (4) test groups which were sacrificed at specific intervals after implantation of four (4) test mammary gels.
The rabbits received each of the four (4) test gels intramuscularly at the dose of .5 cc per site into the spinus rectus muscle.
Four (4) groups of rabbits were sacrificed at 7, 14, 21, and 80 days.
There have been no significant gross pathological findings.
Microscopic exam of the implant sites revealed a localized mile to moderately acute granulomatous inflammatory reaction. This reaction lessened somewhat in the 21-day animals. Because this response was seen in a almost every implant site and was unequally distributed around the trauma of implantation and not due to the test gels.
At the 80 day period, his inflammatory lesion was observed in several instances, however, its' severity was greatly reduced and was present in certain portions of the periphery off the implant site. The remainder of the site was normal. The majority of implant sites were entirely free of any reaction at all. These histopathologic changes observed during the 80 day course of this study were, in our opinion, due to the trauma of implantation and not due to the test gels.
The rabbits exhibited normal appetite, elimination, and behavior and weight gain during the respective test periods.