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AR226-3014 BBS"
Study Title
USP BiocoBpatibility Testing of H-21016 and H-21017
Study CoBpleted on
April 18, 1995
Contracting Laboratory
North American Science Associates, Inc. 2261 Tracy Road
Northvood, Ohio 43619--1397
for
Haskell
E. I. du Font de Neoours and Company
Laboratory for Toxicology and Industrial
Elkton Road, P.O. Box 50 Newark, Delaware 1971A
Medicine
Study Monitor Susan A. MacKenzie, V.H.D., Ph.D., D.A.B.T.
Medical Research Project No.
Laboratory Project ID Haskell Laboratory Report No. 289-95
Page 1 of 11 - Company Sanitized. Does not contain TSCA CBI
Substance Tested; Synonys/Qther Codes:
GENERAL INPORHATION
Control Substance
DuPont HLO 2B9-W
KAmSA Lab. No.; Physical Form;
Purity;
Compositions Contaminantsi
CAS Registry No.;
Substance Tested; Synonyms/Other Codesi
Test Substance
KAaSA Lab. No.; Physical Fora;
Purity;
Compositions Contaminantsi
CAS Registry Ho..' Study Initiated-Coapleteds
02/15/95 - 04/18/95
2 -
Company Sanitized. Does sot eontain TSCA CBSJ
OuPofit Central X----arch ad Devlopwnt B--fecll Laboratory for Toxicology and loduatrial Medicine
DuPont BLO 289-95
April 18, 1995
J. T. Su--ers
DuPont Non-Woven
Old Hickory, Tennessee
USP Biocoapatibillty Testing of H-21016 and H-21017
Attached you will find reports fro North Amrican Science Associates,
Inc.
The results for the H-21016 and H-21017 sanples ares
Test
Results
H-21016
H-21017
Intracutaneous Toxic!ty (USP) - Sodiir Chloride Extract - Cottonseed Oil Extract
Cytotoxicity Testing (Agarose Overlay)
Implantation Test
(USP)
Pass Pass
Non-Toxic
NS"
Pass Pass
Non-Toxic
NS
non significant
J ^ . 6rW)I^. ^ l y SusanA.MaeKenzie, V.M.D., Ph.D., D.A.B.T. Research Toxicologist
Company Sanitized. Does not contain TSCA Ct^
N A i n S A World Leadtr in Teslmi &'( viemi for thy Medical Dtuiee Inm ally
DuPont HLO 289-95
2261 Tracy Raid Northwood. OH 43619 Phone 419f66*9455 FAX 419*6o62954
LAB NO. 95T 05035 00 P.O. NO. LGX 570507
El DU PONT DE NEMOURS & CO
HASKELL LAB FOR TOX & IND. MED
ELK-TON RD PO BOX 50
NEWARK, DE
19714
ATTN: DR. SUSAN A MACKENZIE
ID NO. rt-21016
CYTOTOXICITY - AGARGSE OVERLAY, SOUD
Test Article: H-21016
Test Article Description: Sheet - a 1 cm2 piece
Procedure:
A monolayer of L-929 mouse fibrobtast cells was grown to confluency and overlaid with Minimum Essential Medium supplemented with serum, antibiotics, neutral red, and 2% agarose. The test article, a 0.5 cm x 0.5 cm piece of 725871 H as a positive control, and a 1.0 cm length piece of UP-1 as a negative control were placed on the soKdified overlay surface. Following incubation for 24 hours, the culture was macroscopically examined for evidence of cell decolorization to determine the zone of cell lysis. Any
decolorized zone present was examined microscopically to confirm cell lysis.
Score N (Nontoxic)
Observations Normal eel! morphology in proximity to test sample.
T (Toxic)
Cellular death and degeneration associated with the area beneath the test sample and possibly extended beyond the perimeter of the test sample. Where a zone of lysis was observed, the distance from the edge of the sample to the edge of the zone was measured and reported in millimeters (mm).
Results:
Test/Control Articles Test Article
Score
N
Zone of Lysis tmm)
0
Negative Control: UP-1
N
NAmSA Positive Control: 725871 H
T
Conclusion:
The above test article was nontoxte for L-929 mouse fibrobiast cells under the above described test parameters.
Comments:
Not Applicable. Date Prepared: 3-28-95
Date Terminated: 3-29-95
i-
ComptetdJL,SeL2S-
t^m
Approved.
MG030-110 company Sanitized. Does not contain TSCA CB|.
N A i n S A World Leader in Testing Scrums far Ike Mtilifal Device Industry
DuPont HLO 289-95
2261 Tracy Road Northwood, OH 43619
Phone 41946fr4455 FAX 419>666-2954
LAB NO. P.O. NO.
96T 05036 00 LGX 570507
El DU FONT DE NEMOURS & CO
HASKELL LAB FOR TOX & IND. MEO
ELKTON RD PO BOX 50
NEWARK, DE
1B714
ATTN: DR. SUSAN A MACKENZIE
ID NO.
H-21016
P*ae1of2
USP INTRACUTANEOUS TOXICITY TEST IN RABBITS
Test Article: H-21016
Extracting Conditions:
A 120 sq. on portion was covered with 20 ml of vehiclete) and extracted at 121 C for 1
houris). Control solutions (vehicle without test article) were prepurod in a similar manner. Condition of Extracts:
Testts): SC and CSO clear ControKs): SC and CSO clear
Procedure:
Two healthy New Zealand White rabbits free of significant dermal blemishes were used as
test animate for each extract or pair of extracts. Animate were housed individualy In
suspended cages with daily access to food and water. Prior to infection, the fur was closely clipped from the back and from both sides of the spinal column of each rabbit. A 0.2 ml portion of the test extract was injected tatracutaneously into five separate sites on the right side of the back of each animal white 0.2 ml of the control solution was Injected into five separate sites on the left side. injection sites were examined 24, 48 and 72 hours after injection for erythema and edema. The average tissue reaction to the extract of the test article was compared with the control. The requirements of the test were met if the difference was 1.0 or less and there was no evidence of necrosis or ischemia.
Date Prepared: Date Injected: Date Temiinated:
3-29-95 3-29-95 4-1-95
Camptetad^ii^S^.
VC
^[UlLKU^L^J^ 9 TU013-800
5 -
Company Sanitized. Does not contain TSCA Cl^
BBAiuS^1A*VoiilSLtaderin Testing Serums forlhe Medical Device Industry
DuPont HLO 289-95
2261 Tracy Road Northwood, OH 43619
Phone 41X669455 FAX 419*6662954
-2-
LABNO. 96TOS03EOO
USP MTIIACUTANEOUS TOXIOTY TEST M RARSSVS
SCORING KEY
ER = 0 = 1 = 2 =
ERYTHEMA
No Erythema Very Slight (barety perceptible) WoK^rHned (pink)
3 = Moderate to Severs (red) 4 = Severe (beet redness) to slight
eschar formation (injuries in depth)
Results:
ED = EDEMA
9 = NoEdema 1 Very Sight (barely pereeptfcte) 2 Slight (edg--of area weK-defined
by definite raising) 3 = Moderate (rateed ~ 1 mm) 4 = Severe (raised > 1 mm, may extend
___beyond! the area of exposure)____
24 HHOURS
48 HC3URS
72 H<OURS
Extract
Rabbit No. Site
ER
ED
ER
ED
ER
ED
Sodium
Chloride (SO
86002 85984
Cottonseed Oil (CSO)
86002 85984
Test
0
0
0
0
0
0
Control
0
0
0
0
0
0
Test
0
0
0
0
0
0
Control
0
0
0
0
0
0
Test
2*
1
2*
1
2*
1
Control
2*
1
2*
1
2*
1
Test
1
2
1
2
1
2
,,
Control
1
2
1
2
1
2
Average Test (-) Average Control SC = 0.0 - 0.0
CSO s 1.5-1.5
Difference
0.0 0.0
Comments: Erythema extended beyond the injection sites.
Passes
X X
Fails
tee
Ws-
Completed.
Approved.
-
6
(See MM fi
Company SanBized. Does not contain TSCA CS^
Wor/d Leader in Ttsling Servinm
fw tht Medical Device Industry
DuPonfc HLO 289-95
2261 Tracy Road Northwood. OH 43619 Phone 419666>94S5 FAX 419*666>2954
B DU FONT OE NBtfOURS & CO
HASKaJLLABFORTOX&INO.MEO ELKTON RO PO BOX BO
NEWARK. OE
19714
ATTN: OR. SUSAN A MACKENZIE
LAB NO. P.O. NO.
ID NO.
8BT 06036 00 U3XB70807
H-21016
USP MUSCLE IMPLANTATION TEST IN RABBITS
T--t Arttete: H-2''016
Prwpwtion: Procestuf:
Th< fct rtict* w cut nd trimnrrd to 1 mm x 10 mm. Stsrilizad by cfm.
f t Two h--Rhy adult Naw Z--tand Whir nbbiu weighing t (wet 2.B kg ww uwd B Nnuk. Ttr
trek of --ch ninrl w cKppfl of fur on both id-- of tfr cpircl column. Loo-- iMir w-- iMnova fay
leohol wfp* ftr cNppine nd th* pwcvrfbr*! mtMct-- ww n--ttMtacd. Strip* of frit* twt rticto ww iniDtenfd into tir ri^it pT8vftfaril muKto of ch rbbrt; trip* of USP control pi--tic ww
imptanted in trr !ft pwwfbrl nwele of --ch fbbit.
Th ninrto ww uthMMtized 2 ^V ftf ifflplanftion nd ttr ntir* pw/wfbnl nMMeto on ccch kte of tfr varffan* w-- mmovd. Crow MCtrom of the nund-- ww crrd* to toccte th ifnptanf.
The ti8ue urrounding the implant w xcrnirrd maeroKopieaBy.
R--ult* of MccroMopic Exmintion:
RcbbitNo. 86B4B*
Tart
0 0 0 0
85615
0
0
0
0
Control 0
0
0 0
Score
0
1 2 3 4
0-0.6 0.6-1.0 1.1-2.0 2.1-3.0 &3.1
Scoring Ky Encpcultion
No cp*ul or advr-- reaction (othw than minmrl hmorrhag)
Up to O.B mm cpul or r--ction ar-- 0.8 to 1.0 mm capMite or r--etlon raa 1.1 to 2.0 n-m cputa or faction r--
>2.0 mm cpeula or reaction
Rfction Indox
Not Significant Trc Slight
Modwf
Mcrkd
McrocopK:
Avwge:
0.0
0.0
Avorff (t--t) - Avwga (control) - 0.0
Ttr r--ction w-- not mniticnt compwd to th USP negativ control imptent mafrrl.
ComrrrntB:
Prcviou* u-- hietory trc--bto in laboratory rcord*.
^a
j ^ y , U^ J. Hrinrti.. B8. IJfciMflX
Lj^a-kjL
TU01+.807
7 -
Qompany Sanitized. Does not contain TSCA CB|
World Leader in Testing Sennits fur the Medical Device Industry
DuPont HLO 289-95
2261 Tracy Road Northwood, OH 43619 Phone 419*6669455 FAX 419*666*2954
LAB NO. 95T 05034 00 P.O. NO. LGX 570507
El DU PONT DE NEMOURS & CO
HASKELL LAB FOR TOX & IND. MED
ELKTON RD PO BOX 50
NEWARK, DE
19714
ATTN: DR. SUSAN A MACKENZIE
ID NO. H-21017
CYTOTOXIOTY - AGAROSE OVERLAY, SOUD
Test Article: H-21017
Test Article Description: Sheet - a 1 cm2 piece
Procedure:
A manolayer of L-929 mouse Tibroblast cells was grown to confluency and overlaid with Minimum Essential Medium supplemented with serum, antibiotics, neutral red, and 2% agarose. The test article, a 0.5 cm x 0.5 cm piece of 725871 H as a positive control, and a 1.0 cm length piece of UP-1 as a negative control were placed on the solidified overlay surface. Following incubation for 24 hours, the culture was macroscofHcalty
examined for evidence of cell decotorization to determine the zone of cell lysis. Any
decolorized zone present was examined microscopically to confirm cell lysis.
Score N (Nontoxici
Observations Normal cell morphology in proximity to test sample.
T (Toxic)
Cellular death and degeneration associated with the area beneath the
test sample and possibly extended beyond the perimeter of the test sample. Where a zone of lysis was observed, the distance from the edge of the sample to the edge of the zone was measured a.id reported in millimeters (mm).
Results:
Test/Control Articles Test Article Negative Control: UP-1
Score
N N
Zone of Lysis 1mm)
0
NAmSA Positive Control: 725871 H
T
Conclusion:
The above test article was nontoxic for L-929 mouse fibroblast cells under the above
described ten parameters.
Comments:
Not Applicable. 3ate Prepared: 3-28-95
Data Terminate J: 3-29-95
W ) IM
CB<nMt*dJLie--S-.
8 Company Sanitized. DoeMsGn0o3t 0co-1n1ta0in TSCA CM
K A n i X AWorld Leader in Testing Services fur the Medical Device Industry
DuPont HLO 289-95
2261 Tracy Road Northwood. OH 43619 Phone 419*6669455 FAX 419*666>29S4
LAB NO. P.O. NO.
a6T 0503400 LGX 570507
El DU FONT DE NEMOURS & CO
HASKELL LAB FOR TOX & IND. MED
ELKTONRDPOBOX50
NEWARK. DE
19714
ATTN: DR. SUSAN A MACKENZIE
ID NO.
H-21017
PM1B*2
USP INTRACUTANEOUS TOXICITY TEST IN RABBITS
Test Artiste: H-21017
Extracting Conditions:
A 120 sq. cm portion was covered wnh 20 mi of veh!cle(s) and extracted at 121 C for 1 hour(s). Control solutions (vehicle without test article) were prepared in a sbn8ar manner. Condition of Extracts: Test(s): SCandCSOctear
ControKs}: SC and CSO clear
Procedure:
Two healthy New Zealand White rabbits free of significant dermal blemishes were used as tost animate for each extract or pair of extracts. Animate were housed i idividuatty in suspended cages with daily access to food and water. Prior to injection, the fur was ctosdy
clipped from the back and from both sides of the spinal column of each rabbtt. A 0.2 ml portion of the test extract was injected intracutaneousty into five separate sites on the right
side of the back of each animal white 0.2 ml of the control solution was injected into five separate sites on the left side. Injection sites were examined 34, 48 and 72 hour's after
injaction for erythema and edema. The average tissue reaction to the extract of the test article was compared with the control. The requirements of the test were met if the
difference was 1.0 or less and there was no evidence of necrosis or ischemia.
Date Prepared: Date Injected: Date Temiinated:
3-29-95 3-29-95 4-1-95
ta Comriatad^^Q^
^V
Aaaroved
-
Q
UU)^ilu^^^ Made J. HdMfca. BS. LAT
9 TUtm0i1i3^4.aQwOt
-
Company SariRized. Does not contain 75CA CBI\
N A i n S A Wortd Leads'- in Tenting Srrvicim for the Medical Device Industry
DuPont HLO 289-95
2261 Tracv Road Northwood, OH 43619 Phone 419*666*9455 FAX 419^66*2954
-2-
LAB NO. 95T 05034 00
USP INTRACUTANEOUS TOXICTTY TEST M RABBITS
SCORING KEY
ER ERYTHEMA 0 No Erythema 1 Vary Sight (bcrety perceptible) 2 Wee-defined (pink)
Moderate to Severe (red) Severe (beet redness) to sHaht eschar formation (injuries in depth)
ED 0 -
1 a 2 =
EDEMA
No Edema Very Slant (barely perceptible) Sight (ogee of area well-defined by definite raising) Moderate (raised - 1 mm) Severe (raised > 1 mm, may extend beyond the area of exposure)
Results:
24 H<OURS
48 H(3URS
72H(OURS
Extract
Rabbit No. Site
ER
ED
ER
ED
ER
ED
Test
0
0
0
0
G
0
Sodium
85997
Control
0
0
0
0
0
0
Chloride (SO
Test
0
0
0
0
0
0
85998
Control
0
0
0
0
0
0
Test
2*
2
2*
2
1
1
Cottonseed Oil 85997
Control
2'
2
2*
2
1
1
(CSO)
Test
2*
2
2*
2
1
2
85998
Control
2*
2
2*
2
1
2
Average Test (4 Average Control SC = 0.0 - 0.0
CSO - 1.8-1.8
Difference
0.0 0.0
Comments: Eryttiema extended beyond the sites.
Pasaes X X
Faite
Comoleted_
10 "
JJcompany Sanitized. Does not contain TSC^C^
World /warier in Tinting Strvicvn for the Medical Device h'lttslry
DuPont HLO 289-95
2261 Trxcy Road Northwood. OH 43619
Phone 4194664455
FAX 419*666>2954
LAB NO. P.O. NO.
B DU PONT OE NBUKMMS & CO
HASKELL LAB FOR TOX ft IND. WED
aXTONROPOBOX .0
NEWARK. DE
18714
ATTN; DR. SUSAN A MACKBdZIE
ID NO.
USP MUSCLE IMPLANTATION TEST IN RABBiTS
ST 08034 00 USX 670607
H-21017
TwtArtieto: H-21017
PrpwtKin: Procedure
The t--t articto w-- cut nd trimmad to 1 mm x 10 mm. StfiKzod bv t--m.
f t Two h--lthy adult Nw Z--lcnd Whit* i
Ohms at 1--t 2.6 kg wr u--d ten animate. The
trek of eh ntod we* clipped of fur on both sid-- of the fitful column. LOOM tMir w nmovd by
alcohol wip ftw cfipph'tg nd ttr pravrtbr! musdw ww n--thtizd. Strip* of frito Mticto
wm innptanfd into th right pwvwffanl mucci* of --cii nbtoft; trip* of USP control pi--tic ww
imptanfd in ttc teft pwvrfbr*! miccto of ch rabbit.
Th enimcto w-- utiMiutird 7 day ftw imptaHUtion nd th mir* pfvnebr*! mtMcto on --eh id* of the vrtdbr-- w-- removed. Crow --ctiom of th muwt-- ww mida to toot* th imptent*.
The ti--u* MMrounding th imptent w xjmir.ed mcrocopicafty.
R--ijlt of Macroccapic Examination:
Rabbit No. 86929
T--t
0 0 0 0
85774
0
0
0
0
Control
0 0
0 0
Score
0
1 2 3 4
0-0.6 0.6-1.0 1.1-2.0 2.1-3.0 a; 3.1
Seorwig Key Enoputetion
No euwito or dw-- r--ction (othw ttm minhnal hctnofrtug*)
Up to O.B mm cpute or r--ction i 0.6 to 1.0 mm epul or r--etion
1.1 to 2.0 mm owulo or r--ction >2.0 mm cp*ule or r--ction ur--
R--etion Index Not SiflnitlCTit
Tr--
SNght
Moderf
Marked
MacroMopie:
Avwe*:
0.0
0.0
Avwg* It--tl - Averg (control) -= 0.0
Th r--ction w-- not tionificant a compwd to ttw USP iwflativ control implant mafrial.
Commwif:
Not Applicabto.
cowti^S-
N^
^ Ml.^^.tMMtHI.--.LftT (UAxilOdflxAui^
VTU014-B07
11 -
Company Sanitized. Does not contain TSCA C8^
^^^
