Document re4n26Q9wX3VNm86jBBMnoBE0
FOR DU FONT USE ONLY
AR226-2949
Du Pont HLO 379-90
Itl;loesf t Item)
tiControl Item)
Study Completed On
i
; July 11, 1990
Contracting Laboratory
'Biosearch, Inc. ;3408-50 B Street Philadelphia. Pennsylvania 19134
I for
Haskell
E. I. du Pont de Nemours and Company
Laboratory for Toxicology and Industrial ETkton Road, P. 0. Box 50
Newark, Delaware 19714
Medicine
Laboratory Project ID
Haskell Laboratory Report No. 379-90
Company Sanitized. Does "ot contain TSCACBI
Material Tested:
Medical Research No. Haskell No.: Haskell Test Code:
Biosearch Project No. Physical Form:
Synonyms:
Other Codes:
Material Tested: Medical Research No. Haskell No.: Haskell Test Code: Bi'osearch Project No. Physical Form:
Synonyms:
GENERAL INFORMATION
Du Pont HLO 379-90 Test Material
18,330
90-7004H
White fabric
Control Material
18,331 90-7004H White fabric
company Sanitized. Does not contain TSCA Cffi
Company Sanitized. Does not contain TSCA Cffl
CENTRAL RESEARCH AND DEVELOPMENTDEPARTMENT HASKELL LABORATORYFOR TOXICOLOGY AND INDUSTRIAL MEDICINE
Du Font HLO 379-90 July 11, 1990
Fibers Department Kinston Plant Kinston, North Carc'';na
--10--0--"p--eff--so--n --H--um--an--P--a--tc--h --Te--s|t(Toefst
Item) ;(Control Item)
Attached -is a report from Biosearch, Inc. {Biosearch, Inc., Project No. 90-7004H). Included in the report are patch test methods,-results and
conclusions.
No dermal irritation was iLserved at_anytime_ijLany of thfi^lOl active
aarticipants when tested with
ihe results of Biosearch, Inc. are acceptable and indicate that the Nylon samples are neither skin irritants nor sensitizing agents under the conditions of testing.
QJ^-r. ,U<
Dolores E. Maiek, Ph.D.
Research lexicologist
DEM/1mr/HL09.34
Company Sanitized. Does not contain TSCACBl^
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Subject Number
i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 ^ 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 38 39 40
41 42 43 44 45
Initials
G.R.
M.V.C.
C.S. S.C. M.G. V.F. G.I. R.G. H.S. H.E.C.
E.M.
C.S.L. A.G. J.A. I.J. R.S. D.R. K.L. C.H.E.
K.M. P.H. M.A. M.C. M.S. A.B.
T.R. L.G. K.T C.D.
W.L.
J.R.
M.W. D.H. E.H. D.V. M.S. D.N. B.N.
J.N. K.B. D.R. C.A.M. J.W.
M.M.
J.B.
''-W'^'^y:-:^^ .'.:
: ^ - ,,.,..
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^e(ia^^< i Allergies
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4S
H^meawNr
43
B^4tere^IJmse
58
Homemaker
M
Homemte
33
UNwown
63
Handyman
57
Homema^sr
36
Brick Pointer
33l
Homemaker
57
Homemaker
32
Homemaker
House dust
33
Mechanic
Penicillin
50
Hor'"maker
42
Unemployed
26
Sub-Teacher Aide
21
Homemaker
53
Homemaker
29
Homemaker
60
Homemaker
60
Homemaker
43
Homemaker
33
Homemaker
64
Homemaker
38
Painter
27
Homemaker
21
Housewife
Cats,Penicillin
44
Homemaker
54
Unemployed
64
aeaningMan
60
^ ^memaker
Fiberglass Hayfever
56
Homemaker
58
Grocery Clerk
50;
Homemaker
45
Homemaker
25
Unemployed
32
Cashier
37
Unemployed
35
Nurse's Aide
29
Homemaker
Penidllin,Codeine
40
Homemaker
Starch
20
Homemaker
31
Factory Worker
36
Homemaker
Asthma
%
^
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BIOSEARCH, INCORPORATED - P.b. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 (215) 739-M99
Company Sanitized. Does not contain TSCA CB-l
Du Pont 8M9 379-^^T
Subject
Numbe.
46 47 48 49 50 51 52 53 54
JV.
55 56 57 58 59 60 61 62 .
0f.3i
64 65 66 &7/ A00ft &070 70
71 72
7is1 m74 75 /7&A 77 78
79
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0Q11
m
0& 601J RA
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0O3C 0006 87 0QQ0 O0Q7 90
Initials
C.A.D. N.B. D.A. G.H. J.D.T.
S.K. G.L. E.T.
M.C. E.D.
T.P
M.A. P.A.N. M.M.
J.M. J.W. J.J.H. S.R. K.M. D.F. E.S. W.S. J.L. D.G. M.L.S. R.C.G.
J.cK
D.B.
A.M. C.H. M.F.
J.G. M.B.
W.W. P.D. A.M. P.M. M.M. C.C. D.M.
Kw.. vv,
V.A.O. D.W. M.B. F.F.M.
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Unemployed
59
Cafeteria Worker
56
Homemaker
54
UneiK^lc^fed
51
Homemaker
$7
Hoinemaker
62
Hbmeroaker
S4
Homemaker
14
Homemaker
57
Unemployed
58
Homemaker
30
Unknown
i6
Retired
51
Homemaker
56
Retired
20
Cashier
32
Homemaker
34
Homemaker
46
Housewife
42
Homemaker
42
Homemaker
64
Homemaker
60
Homemaker
38
Homemaker
16
Student
34
Homemaker
17
Student
65
Retired
59
Homemaker
30
Security
55
Ward Clerk
44
Homemaker
41
Homemaker
37
Homemaker
48
Registered Nurse
65
Teacher's Aide
42
Data Entry
48
Unemployed
Allergies
Sulfa Drug
Penicillin
Dust /U'-k*ts Aspirin,Su
BOX 8SW PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739.44W
B10SEARCH. INCORTORATEp P.O.
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Company Sanitized. Does not contain TSCA C9B
E EE R CE
Du pone 10 3V79o-9n02a|
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Subject
Number ~~
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OSEARCH, INCORPORATED...BOXE78
|
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Du Font
BIOSEARCH INQl^)RATED
P.O. Box 85911,Philadelphia, Pepwylvania 19101 T tephoiw (215) 739-4499
Pax: (215)423-9210
HLO 379-90
Project Number: Testing Facility:
Sponsor:
Test Article: Test Article Description: Test Article Received: Study Initiated: Date of Report: lest: Subjects Object of Test:
Method of Test:
90-7004H 1
Biosearch Incorporated 3408-50 "B"!Sireet Philadelphia PA 19134
E.I. Du Pot t De Nemours & Company P.O. Box 5(, Elkton Road Newark. D] \ 19714
H-18,330
White material
05/04/90
05/17/90
Study Completed: 06/20/90
06/21/90
Modified Draize Repeated Insult Patch Test Study in Human
To determine the irritating, fatiguing and sensitizing properties of the test article.
The method employed in carrying out this test was similar to that described in "Appraisal of the Safety of Chemicals in Foods, Drugs and CosmeHcs" by J.H. Draize and published by the Association of Food and Drug Officials of the United States.
The test involved the application of the test article to the upper arms of a group of 107 volunteer subjects. One hundred and one subjects completed the study. These subjects were all determined to be in good! general health and free of any visible skin disease or anomaly in; the area to be patched. Each subject was required to read, understand and sign an informed consent statement.
The test article was tested as supplied.
Company Sanilized. Does nol contain TSCA CBI
^^l'^ Project Numbgr;
E.LDuPonfpeNe^^y Modified Drafcse Rep{^||^
Mfthndnf^t:
Induction Phase
::G;^ril
-ct,.^T.y^r,l..y;^,^....wi;aw^^j!;
Du ipont HL^ 3?T
test article was applied to hypoallergenic doth tope
IN] 08903). The patch remained in
At tfee.^.cndtastfs'^-pe^^:
was removed and the site was
examl|ed ^y":;^-;^^
accordance ^ ^e.,jSj^;\jat?
. Scoring of irritation was in aendix. The subjects were then
resfe^idT a.li^hot^^;
. the skin site was age 'n examined.
A patch wa<^1heit w^d,te^^^me site as previously used. The
secoiridl appUalioa'wa^aBRS^
first and remained in place 24
hours.^.^TrH$/pTOORd^waa?s::'l^ga^i on Mondays, Wednesdays and Fridays urti a series( gf te;ti%i^||3icanonhsad been made. Patch
applications nade on Friday were removed by the subject on Saturday.
the subjects eacsaaucwd the fe ifor -wy dermal response and reported their observa ions prior ft? the Biexf^^i|plicationT.he same site continued
to be used fh roughout tihiestudy.
Challenge Phase
After the 10( 1 application, a aesf :genod of approximately 2 - -: sveeks elapsed after which a challenge application was applied in the same manner and to the same sites desoribed above. A duplicate challenge application vas also applied in the same manner to a virgin site (previously untreated). The challenge application was removed after 24
hours and thi sites were examined'f0r signs of irritation or sensitizarion.
Follow up examinations were conducted at 48 hours after the challenge application.
The subjects nvolved in this study ranged in age from 16 to 65 years of age.
results:
See accompanying table, summary and appendix.
B10SEARCH, INCORPORATED . P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101
Company anitize<(, Does not gpntain T9QA CBI
Project Number: 90-700 "fff^
E.I. Du Font De Neiii^!;i^j|(ci^
Modified Draize ("ondusiori:
Signatures:
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^'^'s^M^^iS
|an Subjecto '
.
a ^ ^ ^ - dy as described
, y.
-^''
test artide is most Sl^ly wit'ft
most likely not a fatisuing agent. tizing agent.
l^@-;%v!%i
'wV.-w.SSS, !^i:i^^1^a'N
.
..^^ &^:.;^
/Xyl^fe^^ Raymond Nitirk, M.EC
Medical Direnor
Karl L. GabrieVl..M.D , Ph.D.
President !
BIOSEARCH, INCOR ATED P.O. BOX 858 PHILADELPSHoIAw, PpEaNnMySYSLVaAnNiItAiz1e91d0.1 Does not contain TSCA CBS
S-r?,'-'3'^
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Project Number;
E.I. Du Font De Men
Modified Draize Rep
Subject
Number
1
24 48
2
24 ^8
3
2^-A8
1
0 0
0 0
0 0
2
0 0
0 0
0 0
3
0 0
0 0
0 0
4
0 0
0 0
0 0
5
0 0
0 0
0 0
. ..... -
--g
7
v""" . ^- 0" 0 0
-
0 0
0 0
8
0 0
0 0
0 0
9
0 0
0 0
0 0
10
0 0
0 0
0 0
11
0 0
0 0
0 0
12
0 0
0 0
0 0
13
0 0
0 0
0 0
14
: 0'
15
3
16
; a
0)
17
<; 18
w
19
u
20
0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0
t^v"
21
ft
22
8-L
23
f3
24
0
0
25
(A
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
3
0
24 = Reading 24 hou
00 48 Reading 48 hou
3
- '= Mot graded
3sa' D c MDiisssceodntianpupeidic; ats 0?
2
^
8
4 24 &B
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Table 1
Induction Phase
5
24J48
1 5
24.J&8
0 ft 0 0 0 0 0 0 0 0
""o" 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 "0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
7
24. 48
0 0 0
0 0 0 0 0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0 0 0
0 0 0 0
0 0
0 0
0 0
-
0
0 0
0 0
0 0
-
0
8
24 <[8
0 0 0 0 0 0 0 0 0 0
----0--TT
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
'
0 0 0 0 0 0 0 * 0 0 0 0 0 0 0 0
%;?^ g S ^
9
1 0
-A8
24.-&8
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
"0 - -0 "0"
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
IA 19101 - (215)
l^f"'j^^B^?-^^?'^^:.. ;;^^:^^^^..:n^^
s^
Prolect Number.
90-7004H
E.I. Du Font De Memours & Company - H-18,
Hodified Oraize Repeated Insult Patch Tea
0
0
o :.'
;
m
^
W
* N' (0
0.
a
o (0
M
3 0
>o 0
is
s-3
0
;>
^Q
fiOI
Subject
Number
26 27 28 29 30
13-11-
32 33 34 35 36 37 38 39 40
*l
1*1
43 44 45 46 47 48 49 50
24 48
24 48
24 48
14
1 2 3 4 0000
0000
0000
0 0
0000
0000
0000
0 0
00 f0\ Ao
00 A0 A()-
0Au 0no
0
A
--u-
0000
0000
0000
0 0
0O0f
0000
0000
0 0
0000
0000
0000
0 0
0000
0000
0000
0 0
0000 0000
00
00
0 0
0000
0000
0000
0 0
0000 0000
00
00
0 0
0000
0000
0000
0 0
0000
0000
0000
0 0
00 00 00 0
24 Reading 24 hours after application 48 Reading 48 hours after previous app
- = Not graded
* cs Hissed application D - Discontinued; subject withdrew from
BIOSEARCH. INCORPORATED -
Tab Ie 1 (C;onti.nilied)
laduc(r^on P;ha-e
5
24-;48
1 6
24.-48
7
24 <L8
8
24 <L
0 0 0 0 0 0 0 0 0 0
----O------y-----
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 U 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
----0" 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0
-
-y------Q---^-.
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
*
*
0
0 0
0
0 0
0
0 0
9
24Ji8
0 0 0 0 0 0 0 0 0 0
o--o
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 0 0 0 0
10 24 48
0 0 0 0 0 0 0 0 0 0
-e- -o-
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 0 0 0 0
on but just before next application for personal reasons.
P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215)
:.^w)"^"
W
N
Y-.
P^o1<?ct Number;
90 -70041H
E.I. Du Font De
Modif ied Draize
N emour 8 & C<oropany - H-l 8 ,330, as R epeat ed In suit Patch T e st Study
supp lied. in H uman 2Subjects
^ ^
Tab Ie 1 (contin ued)
Tnduct ion PI>WS?
Subje ct
Numbe.
1
24A 8
2
2A-AS
3
24 48
4
2A 48
5
2A 48
( 6
24. Afi
7
24A8
( B
24.-A8
9
24 4i
.
10
2AJ&8
51 52 53 54 55
56- .. ... 57 58
59 60
0 0 0 0 0 0 0 0 0 0
.0 . -&0 0 0 0 0 0 0 0
0 0
0 0
0 0
0 0
0 0
0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 L
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0
0 0
0 0
0 0
0 0
0 0
-^ ----01---0-----Q--Q------^ --o----e^-"8-----& --6i----e--^ 1----e- ---- -0--^ r----0---0- ----
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
61
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
62
63
64
0
65
0
3
(6
0
67
0)
^
68
tn
69
Bl
70
ss
71
N'
72
(D
Q.
73
0
74
0 <0
75
<A
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0
0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 .0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3
2^ 24 Reading 24 hours after application
0 0
48 Reading 48 hours after previous application but just before next application
- Not graded
5T
5'
D
Discontinue d; subject withdrew from study for personal reasons.
o!
s
>
0
2
BIOSEARCH, IHCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PIENNSYLV ANIA 19101 - (215)
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Pm ect Number E.I. Du Font D e
Modi fied Draiz e
90 -7004H Ne mour s & Coropany - H-18 .330, as
Re peat ed Ins ult Patch Te st Stiudy
s upp lied.
i n Human Subject S
Ef^S:,?-aE%- ??%
w.asa* '''"W''
^ !x"?sss
,,..
.
.
0
0
0
0)
<
W 0
N'
(6
0.
0
0 (0 UI
0
0 0 3
S"
3
5
0
&
) ^g
Tab Ie 1 (c ont in ued)
indu ipn Pbase
O
Subj ect
Numb &.
1
.2-1-48
2
2A.-&fi
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4
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7
1A 48
8
24 4L8
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10 24 48
76 77 78 79 80
"81 82
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
.
.
-0.- &- ... .n-.--o-
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
-
0
0
0 0
0 0
0 0
0 0
0 D
D D
0 0
0 0
0 0
0 0
0 0
0 0
-
0
0 0
0 0
-
0
0 0 0 0 0 0 0 0 0 0
-.--0-..-0--- -
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 0 0 0 0 0 0 0 0
0 0
0
0 0
j
0 0
0
0 0
0
0 0
0
-00--00----A0
0 0
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D
0 0
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0
0 i\
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0
0 0
0 0
0
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0
0 0
0 0
0 0
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0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
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0
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D
D D
0
0 0
0
0 0
0
0 0
0
0 0
0
0 0
---0000----
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 0 0 0 0 0 0 0 0
--00 --
0 0 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0
0---
0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
-A -0.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D D 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
. .-;OL-
0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0
-0-.
0 0 0 0 0 0 0 0 0 0 0 0
D 0 0 0 0
24 - Reading 24 hours after application 48 = Reading 48 hours after previous application but just before next
- = Not graded
D = Discontinued; subject withdrew from Study for personal reasons.
application
BIOSEARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA ] 101 - (215)
^ Wj
PrPi ect Number!
90 -70041a
E.I. Du Font De Nemour S & Ccampany - H-18 .330. as supplied.
Modi fled Draize Repeat ed Intsuit Patch Te st Stt dy in Hunan Subjects
Table 1 (continued)
.'
Induction Phase
O
Subj ect
1
2
3
4
5
6
7
8
9
10
Numbjer
24 4 a
24.-4fi
24 48
21 48
24 48
24 48
24 48
24 48
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24 48
101
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0000
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103 104
0 0 0 0
0 0 0 0
00 00
0 0 0 0
00 00
00 00
0000
00 00
0000
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105
- 0 106
0 0 0 0
0 0 0 0
0000
0 0 0 0
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0000
00
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0
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0 V
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0
3
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24 - Reading 24 hours after application
p. 48 Reading 48 hours after previous app licatj on but just before next application
0
-- t= Not graded
0 (0
D - Discontinued; subject withdrew from study for personal reasons.
U1
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HLO 379-90 Page 9 of 9
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i
Project Number 90-7004H
Du Pont
E.I. Du Font De Neinours & Conpany - H-18,330
Modified Draize Repeated Insult Patch Test Study in Human Subjects
HLO 379-90
Appendix
GRADING SCALE luman Patch Test Studies
Reading
0
1+ 2+ 3+ 4+
Ir^rpretetion
nejgative sufepidous
slighterythema w^Udefined erythema
erythema with induration erythema with ulceration
DEFINITIONS*
Sensidzation is a phenomenon which manifests itself by local effects on either skin or
mucous membranes. It differs from primary irritation in that it may also involve tissues
remote from the site of application. These reactions represent an allergy to a chemical which is not obtained on first contact, but requires a number of prior exposures for development.
Repeated patch applications of substances to both man and animals reveal that certain substances which, at a given concentration, do not produce primary irritation may elidt severe skin reactions after a nufanber of exposures. Nevertheless, these reactions may not be considered inddents of sensitization since after 10-14 days of rest the skin recovers its original resistance to injury by the substance. For the lack of a better term such reactions have been called "skin fatigue".; This latter term is a misnomer in that it does not imply a condition in which the skin has lost significant normal physiological function. This phenomenon consists of a subde change in which die skin no longer exhibits its original refractorines.. or resistance to the continued or repeated action of an agent.
* Draize, J.H. 1959. Appraisal Of the Safety of Chemicals in Foods, Drugs and Cosmetics.
In DERMAL TOXICTTY, p.46-53. Topeka, Kansas: Assodation of Food and Drug Officials
of the United States.
'.
BIOSEARCH. INCORPORATED P.O. BOX 8598 PHILADELPHIA, PENNSYLVANIA 19101
Company Sanitized. Does not contain TSCA CBS
-'^'.--^i'.syrsi! Pfl.i?;?^;.!:-?"^"!-.^^^^"?'!^^
pu Pent
ORATED
ylvania 1^101
'9
Project Number: Testing Facility:
Sponsor-
Test Article: Test Article Description: Test Article Received: Study Initiated: Date of Report: Test: .Subjects Object of Test:
Method of Test:
3408^B"^t ^: Biosearc ij&^MitQraited,;-.'"'.'-'^-
.^
'
.'
'.I
Phiia4^>hia,^19?M; 0 ^
'
-'
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E.I. Du I'pnt De Nemours^Cei^pany
P.O. Box 50, E|kt9n Road
;
Newark, DE 19714
H-18,331
White material
05/04/90 ( 05/07/90
Study Completed: 06/20/90
06/21/90
Modified Draize Repeated Insult Patch Test Study in Human
To determine the irritating, fatiguing and sensitizing properties of the test article.
The method employed in carrying out this test was similar to that described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmeettiiccs" by J.H. Draize and published by the Association of Food and Drug Officials of the United Slates.
The test involved the application of the test article to the upper arms of aa| group of 107 volunteer subjects- One hundred and one subjects completed the study. These subjects were all determined to be in g( >cd general health and free of any visible skin disease or anomaly n the area to be patched. Each subject was required to read, und erstand and sign an informed consent statement.
The test article was tested as supplied.
Company Sanitized. Does not contain TSCA CBI
Project Number- 90E.I. Du Font De Nempiirs }
f^Sf-s, '; "^tWW. Ks^ShsfS
?3Ba WW^6: Du Porrt^'' yage^o^
Modified Draize Repeated In^grfcK:g^^^
':M
i Subjects
Method of Test: Induction Phase
w ^ Approximatelyft
the ^;^iaid..<aEWiN^
(Johnspn ^Jeh; 6oi,^ieiv 8|
place fbr^fteilrsi.i';^ ^
'
_^
of test article was applied to licel hypoaliergenic doth tape 108903). The patch remained in
id^lN^E)^ At the enii.iof'this.^pb^il^
as removed and the site was
examined fen any a^;^i|" ' |oias|i|Scoring of irritation was in
accordance with the:;^^
"^'-'^Tidix. The subjects were then
rested for a 24 liow^N^:?
e skin site was again examined.
A patch was men applied .t^o
site as previously >-jed. The
' -
-
second
a
p
p'..
l.
i
c
a-L
'
t
i
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n''f.t^".'
...!.-AA.
"rat and remained in place 24
hours. This p:oced)ure w^^e^altei^ Mondays, Wednesdays and
Fridays until . senes pf ^ic), 'app^tions had been made. Patch
applications made on Friday weire removed by the subject on Saturday.
Thu subjects examined the site for sUf dermal response and reported
their observations prior to the next application. The same site continued
to be used thrpi ighput the study.
Kk
Challenge Phase
2-3 After the 10th ipplication, a rest pen^id of approximately
weeks
el apsed aft, er which a challenge app^iation was applied in the same
manner and to the same sites descried above. A duplicate challenge application wai also applied in the same manner to a virgin site (previously unt eated). The chaillenge application was removed after 24
hours and the sites were examined for signs of irritation or sensitization.
Follow up examinations were conducted at 48 hours after the challenge
application.
Results:
The subjects involved in this study ranged L. age from 16 to 65 years of age.
i
See accompanyijtnagble, summary and appendix.
3IOSEARCH. INCORPORAT]ED P.O. BOX 8598 PHILADELPHIA, PENNSYLVANIA 19101
Company Sanitized. Does not contain TSCA CB8
Project Number- 90-7004H
Du Pont HLO 379-90
Page 3 of 9
E.I. Du Font De Nemours & Comply - H-18,331
Modified Draize Repeated Insult PajtcThest Study in Human Subjects
Conclusion:
From the results obtained in this study as described above with the particular group of subjects tested, the test article is most likely not a primary skin iirrnritant. The test article is most likely not a fatiguing agent. The test article i most likely not a sensitizing agent.
Signatures:
Submitted by Bibsearch, Incorporated:
Bfederick Urbafch, M.D.
Consultant Deirmatologist
(JJU^H^^^
^nnand Affrinjie,, Study Director
f^M^^U/^w^
Raymond Mark, M.D. Medical Director
Karl L. Gabriel, V.M.D., Ph.D.
President
Company Sanitized. Does not contain TSCA CBi
BIOSEARCH, INCORPORATED - P.O. BOX E59S - PHILADELPHIA. PENNSYLVANIA 1910)
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''^'"^S^B^P-^SisS^
PrnjBef Number;
90-7004H
E.I. Du Font De Memours 6 Company - H-18,331, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
S^SSf^S^
ss^:^-ly^t .'"/""
Table 1 (continued)
Induction Phase
Siubjtset
1liirnhfiX
1
24 48
2
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3
24 48
t >
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26 27 28 29 30
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34
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35
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36
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37
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39
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40 00 41 3 42 "001 43
^ 44
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0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 00 0 0Q 0 00 0 0D 0
30) 46
47
N" (D
40
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 * 0 0
0 0
*
0 0
0. 49
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
a 50
0
0 0
0 0
0 0
0 0
0 0
0 0
-
0
0 0
w
W 24
3
Reading 24 hours after application
0 48 Reading 48 ho urs after previous application but just before next appliccaation
8 - cs Not graded
3 * c Missed application
SD
5"
Discontinued;
subj ect withdrew from Study for personal reasons.
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
a.. a .--... -0-.0.
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
) 0
0 0
0 0
0 0
0 0
D D
D D
0 0
0 0
0 0
0 0
0 0
0 0
0-5i
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Tab!Ie 1 (continued)
l a duct-LonJEtl a s e
0
I
o
OK
1 s
a.
0
0 (D 01
0
0 0
in"
I
g
3
Subj ecc NumbX
51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
1
24 4 &
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2
24. 4fl
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
-
0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
3
24 4B
0 0 0 0 0 0 0 0 0 0 0 &0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0' 0 0 0 0 0 0 0
4
24 4S.
0 0
0 0
0 0
0 0
0 0
0 -0-
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
^
0
0 0
5
1L &fi
0 0
0 J
0 0
0 0
-
0
- --Xl n
0 0
0 0
0 0
Q 0
0 0
0 0
0 0
0 0
-
0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
e 5
2A--Afl
0 0
0 0
0 0
0 0
0 0
n
n
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
.
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
7 24 4 &
0 0 0 0 0 0 0 0 0 n JQ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3
2A.-48
0 0 0 0 0 0 0 0 0 0
-..--n-n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
9
24 4.
10
1A-&a
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
....JS-..-0-. -.-.-.n. -Q- - .
0 0
0 0
0 0
0 0
0 Q
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
24 - Reading 24 hours after applicaticin 4-- 8 13 - MRoet agdrinagded48 hours after previous eipplicat! on but just before next application '
n c Discontinued; subject withdrew from study ?or personal reasons.
DIOSEARCH, INCORPORATED - P .0. BOX B59B - PHILADELPHIA. PENNSYLVANIA 19101 (215)
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Tabin 1 (c onfcinLled)
Subject
Mumber
76 77
78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
100
1 24 48
0 0 0 0
0 0 0 0
0 0 0 0 0 0
0 0 0 0
0 0 0 0
0 0
0 0
0 0
0 0
0 0
0 -
0 0
0 0
0 D
0 0
0 0
0 0
-
0
0 0
2 24 48
0 0
0 0
0 0
0 0
0 0
0-10
0 C
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
-
0
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0 0
D D
0 0
0 0
0 0
0 0
-
0
JnducjLion Phase
3
24 48
4 24 48
5 24 48
6
24 48
7
24 48
8
24 4B
9
?-4 48
10 24 48
0 0
0 0
0 "
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
-V--0- V -y-- -
0 0
0 0
------Q---Q0 0
0 0
0 0
0 0
0 0
0 0
0 0
Q 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
D D
D D
D D
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0
--&--0----- --Q-----Q---------.^-..Q.-.-0---Q--...-0.....^.
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
-
0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0
-
D D
D D
D D
D D
D D
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0
-
24 = Reading 24 hours after applicat ion 48 = Reading 48 hours after previous application but just before next
as Not graded
D - Discontinued ; subject withdrew from study for personal reasons.
application
BIOSEARCH. INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215)
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E.I. Du Font De Nemours & Company -H-18,331
Modified Oraize Repeated Insult
Test Study in Human Subjects
HLO 379'90
Appendix
Reading
0
. 1+ 2+ 3+ 4+
! GRADING SCALE
Human Patch Test Studies ! i . !
Interpretation
negative suspicious slight erythema well defined erythema eryth'ema with induration 'rythiema with ulceration
DEFINITIONS*
Sensitization is a phenomenon which manifests itself by local effects on either skin or mucous membranes. It differs frofo. primary irritation in that it may also involve tissues remote from the site of application. These reactions represent an allergy to a chemical which is not obtained on first contact, but requires a number of prior exposures for development.
Repeated patch applications of substances to both man and animals reveal that certain substances which, at a given concentration, do not produce primary irritation may elidt severe skin reactions after a number of exposures. Nevertheless, these reactions may not be considered incidents of sensitization since after 10-14 days of rest the skin recovers its original resistance to injury by the;substance. For the lack of a better term such reactions have been called "skin fatigue"; This latter term is a misnomer in that it does not imply a condition in which the skin has lost significant normal physiological function. This phenomenon consists of a subtle change in which the skin no longer exhibits its original refractoriness or resistance to the continued or repeated action of an agent.
* Draize, J.H. 1959. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In DERMAL TOXICITY, p.46-53. Topeka, Kansas: Association of Food and Drug Officials of the United States.
Company Sanitized. Does not contain TSCA CB1
B103EARCH, INCORPORATED - P.O. BOX 6598 - PWLADELPHIA, PENNSYLVANIA 19101