Document nmBeqxy3X3dwrzRJMBGKqKMb8
t i FOR DU PONT USE ONLY
Study Title
AR226-2932
Du Pont HLO 408-87
Author John E. Henry
Study Completed On July 30, 1987
Performing Laboratory E. I. du Pont de Nemours and Company, Inc. Haskell Laboratory for Toxicology and Industrial Medicine
Elkton Road, P. 0. Box 50 Newark, Delaware 19714
Medical Research No.
Laboratory Project ID Haskell Laboratory Report No. HLO 408-87
Page 1 of 2
QoMpmySanftbed.DoesnoiqqntalnifgCA3*
CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE
cc:
July 30, 1987
L 1CHEMICALS AND PIGMENTS DEPARTMENT
TECH LABORATORY
0
TEST) AND I l TEST)
Attached is report HLO 408-87 (Biosearch, Inc., Project Number 37^5670H). Included in the reports are patch-test methods, results and conclusions.
The test materials were judged to be neither primary skin irritants nor sensitizing agents when tested by a repeated-insult patch test.
i
J. E. HENRY TECHNOLOGIST
JEH:smk:HL07.49 Attachment
]
Sampang Sanitized. Dees mAoorrtsfm TSCA Q _
ULO- 4os
Protect Nuaber: 87-5870H R T rill Pont de Nemours 8
Coapany.
Inc.
(Refer
to your
letter of 05/12/87)
Modified Dralze Repeated Insult Fateh Test Study in Huaan suojeccs
Subiect List
Subject Nuaber
Initials
Sex Age CoaDlexion Allergies
1 2
M.A. F..A.
F 58 Mdius F 68 Fair
"
V. A .
F 57 Fair
4
A.A.
F 65 Mdius
"
5
L.B.
F 48 Fair
6 R.M.B. F 28 Mdius
--
7
M.B.
F 28 Fair
--
8 9 10
J.B.
F 44 Fair
F.M.B. M 28 Mdius
R.P.
M 46 Mdius
cats ~~ ~
11
T.B.
M 57 Medium
12
SB.
F 49 Medium
--
13
J.B.
F 54 Fair
14 D.M.B. F 56 Medium
~
15
M.B.
F 31 Fair
16
K.C.
F 35 Medium
17
D.C.
F 30 Fa ir
'
18 J.A.C. F 25 Fair
19
C.C.
F 41 Fair
'
20
C.D.
F 49 Medium
21
B.D.
F 17 Medium
_
h
22
1).D .
F 49 Fair
23
K.D.
F 27 Fair
24
k .i .r>.
F
33 Medium
25
K.D.
F 43 Fai :
26 '
A.M.I).
F
29 Fair
27
M.D.
M 31 Medium
28
M.K.
F 44 Med ium
29
B.E.
F 64 Fair
30
R.E.
F 60 Medium
31 J.M.F. M 33 Medium
32
L.F.
F 28 Fai.
33
S.F.
F 39 Fair
34
J.G.
F 28 Fair
35
S.G.
F 18 Fair
36
B.H.
F 22 Fair
37
D.H.
F 17 Medium
38
F..H.
F 41 Fair
39 E.A.H. F 15 Medium
40
M.H.
F 49 Medium
41 42
S.H. J.H.
F 32 Medium F 43 Fair
bee stings
43
D.H.
F 31 Medium
44
1 .1 .
F 57 Medium
45
C. J .
F 35 Fair
46
A.K.
F 54 Fair
nylon
47
C.K.
F 36 Fair
48
B.K.
F 57 Fair
49
K.L.
F 26 Fair
)/
50 51
M.L. S.L.
F 28 Medium F 32 Fair
dust
52
D.L.
F 16 Fair
P.O. BOX 857B - PHILADELPHIA. PENNSYLVANIA 17101 - (215) 737-4*97
ilHlTflti
.. TgrA * *
rre a st
. . . <er,V V T
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Subject List (continued)
Subject Nuaber
Initials
Sex Age Complexion Allergies
53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 71
75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103
G. L. A. L . P.M. R.A.M. M.M. M.M. R.M. E.M. A.E.M. F..M. J.M. R.M. H.M. J.M. M.M. P.M. J.P.M. J.N. M. N. D .0. N. O. M.P. J.L P. C.G P. D.P. R.P. S.P. J.Q. R R. S.R. MR. J.R. K.R. A.K.
L.R. D.S. L.S. C.S. M.S. M.S. M.A.S. R.S. H.S. M.S. K.T. C.T. B.T . A .V . H.W. D.W.
s.z.
F F F F F F F F F F F F
F F F F M F M F F F M M F M F F F F F M F F F F F F F F F F
F F F F F M M F F
35 49 33 35 17 18 42 30 53 64 54 46 43 61 44 54 53 37 17 28 52 25 50 53 26 27
16 19 25 52 21 61 42 29 39 64 35 36 42 29 30 51 54 48 17 25 33 66 55 28 34
F a ir F a ir Mediua Medium
Mediua
F a ir Mediua Fair Fair Mediua Fair Medium Medium Medium Med iurn Fair Medium Fair Fair
Fair Fa ir Med ium Med ium Fair Fair Med ium Pair Medium Medium Med ium Medium Fair Medium Medium Fair Fair Medium Fair Medium Medium Fair Mediua Medium Medium Fair Fair Fair Mediua
Fair Medium Fair
penicillin penici 11 in
penici 11 in
Indocine penici 1iin
penici 11 in
~ poison ivy
*" " -
-- ~ hayfever penici11 in penici11 in
--
" "
" seafood "
ytff-
BIOSEARCH , INCORPORATED - P.0. BOX B59B - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499
//////\\\
////// /// /// \\\///
Telephone: (215) 739-4499
Project Number:
87-5670H
Testing Facility:
Biosearch Incorporated 3408-50 "B" Street Philadelphia, PA 19134
Sponsor :
F..I. du Pont de Nemoi-rs & Company, Haskell Laboratories P.O. Box 50, Elkton Road Newark, DE 19714
Inc.
Test Article:
16,759
Test Article Peser ipt ion :
Blue fabric
Test Article Received: 05/14/87
Study Initiated:
05/27/87
Study Completed: 07/02/87
Date of Report:
07/06/87
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Obiect of Test :
To determine the irritating, fatiguing and sensitiz ing properties of the test article.
Method of Test:
The method employed in carrying out this test was similar to that described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" 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 103 volunteer Cauca sian subjects. These subjects were all determined to be in generally good health, 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.
Modified Draize Repeated Inault Patch Test Study in Human Subject
Method of Tet: (continued)
Approximately a one Inch square portion oi test article wa applied to the appropriate kin ite and covered with 2" >ericel hypo-allergenic cloth tape (Johnson & Johnsor . New Brunswick, N..T. 08903). The
patch remained in tlace for 24 hours.
At the end of this period, the patch was removed and the site was exami-.ed for any dermal response. Scor ing of irritation as in accordance with the scale in the Appendix. The subjects were then rested for a 24 hour period after which the skin site was again examined. A pater was then applied to the same site as previously used. The second application was identical to the i.rst and remained in place 24 hours. This procedure was repeated on alternate days untfrl a series of ten applications had been made. The same site continued to re used throughout the study period as long as no irritation or only minimal irritation (1+ ) was seen at'.er each 24 hour rest period. If ,, e a t e r irritatio- (2+ or more) was noted then the subject was either rested or the contact site was changed at the disiretion ot the investigator.
Approximately a i to 3 week rest period then elapsed
after which a challenge application was applied in the
same manner and tc the same sites described above. A
duplicate challerte application was also applied in
the same manner to a virgin site (previously
untreated) on e other arm.
The challenge
application was r ^ o v e d after 24 hours and the sites
w-re examined or signs of irritation or
sensitization. fellow up examinations were conducted f . . . -K. challen ge a p p lic a tio n .
The subjects invoked in this study ranged in age from 16 to 68 years ol -ge.
See accompanying f.ble. summary and appendix.
not eontaln TSSA 6? I
y
BIOSEARCH* INCORPORATED - P.0. BOX 6598 - M.AOELPHIAi PENNSYLVANIA 19101 - 1215 739-4*99
Modified Dralze Repeated Insult Patch Test Study in Human Subjects
Conclusion: Signatures ;
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 irritant. The test article is most likely not a fatiguing agent. The test article is most likely not a sensitizing agent.
Submitted by Biosearch, Incorporated:
lohn F. Wilson, M.D. ^Consultant Dermatologist
ark, M.D. Medical Director
___
Karl L. Gabriel, V . M " . , Ph.D. President
I
BIOSEARCHi INCORPORATED - P.0. BOX 859B - PHILADELPHIAi PENNSYLVANIA 19101 - (215) 739-4499
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,759, as supplied.
Paga 4 of 9
OCM'
Modified Draize Repeated Insult Patch Test Study in Human Subjects m 6n
5ni Table 1
Initial Exposure
*0a>Hm0
Subject Number
1 24 48
2 24 48
3 24 48
56 789 48 24 48 24 48 24 48 24 48 24 48
1 00 00 0 0 00 00 0 0 00 00 0
2 a3
00 00
00 00
00 00
00 00
00 00
00 00
00 00
00 00
0 0
C0XD OECP
4 5 6
CD 7
00 00 00 00
00 00 00 00
00 00 00 00
00 00 00 00
00 00 00 00
00 00 00 0G
00 00 00 00
00 00 00 00
0 0 0 0
a8
00 00 00 00 00 00 00 00 0
9 00 00 0 0 00 00 0 0 00 00 0
10
0 0 0 0 0 0 0 0 0 ft ft ft 0 0 ft ft ft
5Om
11 12
ai 13
? 14
m 15
zu-rt<
16 17
>z 18
> 19
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
0 0 0 0 0 0 0 0 0
o 20
00 00 00 00 00 00 00 00 0
21 a 22
00 00
00 00
00 00
00 00
00 00
00 00
00 00
00 00
0 0
23 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3 24
00 0 0 00 0
U<s0j 25
00 00 00 0
(t&(00
24 " Reading 24 hours after application
0 0
00 00
00 00
00 00
00 00
0 0
48 Reading 48 hours after previous application but just before next application
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
10 24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 0 \. 00 00 ft ft 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00
00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
BIO S EA RCH . INC O R P O R ATE D P O . BOX 6 5 9 8 P H IL A D E LP H IA . P E N N S Y LV A N IA 19101 ( * 1 5 ) 7 3 9 - 4 4 9 9
Project Humber: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,759, as supplied.
Modified Draise Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
Subject Number
26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
1 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
2 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
3 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
4 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Initial Exposure
56 7 24 48 24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0.0 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
9 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 , 0 0 0 00 00 00 00
10 24 48
Challenge
Original Virgin Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
0o 0o 0o 00 00 00 00 00 00 00 0o 00 00 00 00 00 00 00
00 00 00 00 00 00 00
24 Reading 24 hours after application 48 e*^*-nR hours after previous application but just before next application
Project Number: 87-5670H
E.I. du Pont de Nemours 6 Company, Ino. - 16,759, as aupplifil.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
BIOSEARCH. INCO RPO R A I ED . PO. B O X B 59B
Table. 1 (continued)
Subject Number
5) 52 53 54 55 56 57 58 59 60 61 62 63 64 65
66
67 68 69 7C 71 72 73 74 75
1 24 48
00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
2
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 48
00 00 00 00 00
00
00 00 00 00 00 00 00 00 00 00 00
00
00 00 00 00 00 00 00
4 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Initial Exposure
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
c0
00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
9
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Challenge
10
Original Virgin Site Site
24 48 24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00
00 00
00 00 00 00 00
P H IL A D E LP H IA . P E N N S Y LV A N IA 19101
1215)739-4499
24 - Beading 24 hours after application 48 - Reading 48 hours after previous application but just before next application 'S * .
Page 6 of 9
fk)fl
O'
Project Number: 87-5670H
K.I. du Pont de Nemours & Company, Inc. - 16,759, as supplied.
Modified Oraise Repeated Insult Patch Test Study in Human Subjects Table 1 (continued)
Subject o Number
76 77 78 79 80 81 82 83 84 R'. 86 87 88 89 90 91 92 93 94 95 96 97 98
99 100
1 24 48
2 24 48
3 24 48
4 24 48
Initial Exposure
56 24 48 24 48 24 48
8 24 48
9 24 48
10 24 48
Challenge Original Virgin
Site Site 24 48 24 48
00 00 00 00 0U 00 00 00 00 it II 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00
00 00 00 00 00 00 00 00 00
II II
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
II II
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
03 00 00 00 00 00 00 00 00 11 II 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00
00 00 00 00 00 00 00 00 00
II II
00 00 00 00 00 00 00 00
00 00 00 00 00 00 0n
00 00 00 00 00 00 00 00 nn
II II
00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 nn
II II
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 nn
II II
00 00 00 00 00 00 00 00
00 00 00 00 00 00 0n
00 00 00 00 00 00 00 00 nn II o 00
00 00 00 00 00 00 00
00 00 00 00
00 00 nn
00 00 00 00 00 00 00 00 nn ou 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 nn u 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 n0 uu 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00
| 24 Reading 24 hour after application 48 Reeding 48 hours after previous application but just before next application
Page 7 of 9
P H ILA D E LP H IA . P E N N S Y L V A N IA 19101
ef fes
On
Project Number: 87-5670H E.I. du Pont de Nemours & Company, Inc. - 16,759, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
0von
Subject Number
9
mH
O
101
a 102 103
1 24 48
00 00 00
48
00 00 00
3 24 48
00 00 00
4 24 48
00 00 00
Initial Exposure
5 24 48
6 24 48
7 24 48
00 00 00
00 00 00
00 00 00
8 24 48
00 00 00
9 24 48
00 00 00
10
24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00
00 00 00
Page 8 of 9
CM !
rsi
I go
I
? mTzzi<r<>nJ
Z
> <o 6
24 - Reading 24 hours after application 48 Reading 48 hours after previous application but just before next application
(0
B IO S E A R C H . IN C O R P O R A T E D P.O 3CX 0 5 9 8 P H IL A D E L P H IA P E N N S Y L V A N IA 19101 1215) 7 3 9 -4 .
Project Number: 87-5670H
K . I . J u l*i h i I il l" N f in m n a & C iin i|> riii v , l u t .
I ( , / ' > ' , n n n | j . I 1 .1 .
Modified Draize peated Insult Patch Test Study in Human Subjects
Suranary of Table 1
Initial Exposure
1 2 3 4 5 6 7 8 9 10 Readings 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48
0 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103
Challenge
Original Virgin
Site
Site
24 48
24 48
103 103 103 103
24 " Reading 24 hours after application 48 *= Reading 48 hours after previous application but just before next application
Modified Draise Repeated Ineult Patch Teat Study in Human Subject
GRADING SCALE Human Patch Teat Studies
Read ing
0 + 1+ 2+ 3+ t+
Interpretation
negat ive suspicious slight erythema well defined erythema erythema with Induration erythema with ulceration
DEFINITIONS*
Sensitization 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 ^ t i o n s represent an allergy to a chemical which is not obtained on first contact, but requires a number of prior exposures for development.
BIOSBARCH INCORPORATED
III
/// /////A\\
U H U /// III \\\///
P.O. Box 8598, Philadelphia. Pauartvaaia 19101 Tdephoao: (2151 739-4499
Project Number: Testing Facility:
87-5670H
Biosearch Incorporated 3408-50 "B" Street Philadelphia, PA 19134
Sponsor :
F.I. du Pont de Nemours & Company, Inc. Haskei1 Laboratories P.O. Box 50, Elkton Road Newark, DE 19714
Test Article:
16,760
Test Article Peser iptIon :
Blue fabric
Test Article Received: 05/14/87
Study Initiated:
05/27/87
Study Completed: 07/02/87
Date of Report: Test:
07/06/87
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Object of Test:
To determine the irritating, fatiguing and sensitiz ing properties of the test article.
Method of Test:
The method employed in carrying out this test was similar to that described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" 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 103 volunteer Cauca sian subjects. These subjects were all determined to be in generally good health, 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 w a s tested as supplied.
CO1
a**
ft* eo'
Project Niwhtr!
S7-S670H
Page 2 of
E.I. du Pont do Nemours 6 Company, Inc. - 16,760
Modified Draize Repeated Ineult Patch Teat Study In Human Subjects
Method of Test: (continued)
Results :
Approximately a one inch square portion of teat article was applied to ..he appropriate skin site and covered with 2H Deraicel hypo-allergenic cloth tape (Johnson & Johnson, New Brunswick, N.J. 08903). The patch remained in place for 24 hours.
At the end o: thio period, the patch was removed and the site was examined for any dermal response. Scor ing of irritation was in accordance with the scale in the Appendix. The subjects were then rested for a 24 hour period after which the skin site was again examined. a patch was then applied to the same site as previously used. The second application was identical to the first and remained in place 24 hours. This procedure was repeated on alternate days until a series of te- applications had been made. The same site continued to be used throughout the study period as long as -.j irritation or only minimal irritation (1+ ) was seei after each 24 hour rest period. If greater irritation (2+ or more) was noted then the subject was either rested or the contact site was changed at tr.e discretion of the investigator.
Approximate), a 2 to 3 week rest period then elapsed
after which a challenge application was applied in the
same manner and to the same sites described above. A
duplicate challenge application was also applied in the same Banner to a virgin site (previously
untreated) in the other arm.
The challenge
application was removed after 24 hours and the sites
were exami-.ed for signs of irritation or
sensitizatio'.. Follow up examinations were conducted
at 48 hours otter the challenge application.
The subjects involved in this study ranged in age from 16 to 68 years of age.
See accompanying table, summary and appendix.
BIOSEARCH. INCORPORATED - P.0. BOX B59 - PHILADELPHIA. PENNSYLVANIA 191D1 - (215) 739-4499
Project Number:
87-3670H
Page 3 of 9
E.I. du Pont de Nemours 4 Company, Inc. - 16,760
Modified Dralze Repeated Insult Patch Test Study in Human Subjects
Conclusion: Signatures:
From the results obtained in this study aB described above with the particular group of subjects tested, the test article is most likely not a primary skin irritant. The test article is most likely not a fatiguing agent. The test article is most likely not a sensitizing agent.
Submitted by Biosearch, Incorporated
Raymond jlark, M .D . Medical*nirector
Karl I.. Gabriel, V.M.D., Ph.D. President
) B105EARCH. INCORPORATED - P.0. BOX 0598 - PHILADELPHIA. PENNSYLVANIA 191Q1 - (215) 739-4499
Project Number: 87--5670H F. . 1 . r|ti Po nt rfi' N om on iP * I ' *m|.an V , 1*' -
W, /<<, an n .j. 1. 1 i < .1 .
Modified Draixe Repeated Insult Patch Test Study in Human Subjects
0 5
(A
Vr1> Table 1
zn ouo 0 Subject
5-* Nuaber
1 24 48
2 24 48
3 24 43
4 24 48
Initial Exposure
56
24 48 24 48 24
48
P O BC< 9 5 9 8 . P H IL A D E L P H IA . P E N N S Y L V A N IA 19IOI
1 2 3 4 5 6
7
8
9 10
1112
13 14
15 16 17 18
19 20 21
22
23 i 24
3 25
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00 00 00 00 00 00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 1) 0 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 1) 0 00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00 00 00 00 00 00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 oo 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00 00 00 00 0u 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
8 24 48
00 00 00 fl 0 u0 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00
9 24 48
00 00 00 n0 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
10 24 48
Challenge Original Virgin
Site Site 24 48 24 48
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
0 o'
00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 " Reading 24 hours after application 48 " Reading 48 hours after previous application but just before next application
^ Confi
vv
Project Number: 87-5670H E.I. du Pont de Nemours & Company, Inc. - 16,760, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
09
tn>n ox X
o Subject
' Number
26 27 28 29 30 31 32 33 34 35 36 37 33 39 40
41 42 43 44 45 46 47 48 49 50
Table 1 (continued)
1 24 48
00 00 00 00 00 00 00 00 00 00 00 0 0. 00
00 00 00 00 00 00 00 00 00 00 00 00
2 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00
Initial Exposure
3 24 48
4 24 48
5 24 48
6 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00
00
00
00
00
00
00
00
00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00
00
00
00
00
00
00
00
00
00
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00
00
00
00
00
00 0n
00
00
00
00
7 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00
9 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00
10 14 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00
S
24 - Reading 24 hours after application 48 m Rending 48 hours after previous application hut
lust before next
appiicat ion
Page 5 of 9
Of
Page 6 of 9
B io s e a r c h in c o r p o r a t e d p o 0 0 x 0 5 9 0 Ph ila d e l p h ia . Pe n n s y l v a n ia 19101 ^'i^i 739 4499
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,760, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Subject Number
51 52 53 5A 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
1 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
>
24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
3 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
4 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Table 1 (continued)
Initial Exposure
5 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
6 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
7 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
9 24 48
00 00 00 00 00 00 00 0C 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
10
24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 Reading 24 hours after application 48 - Reading 48 hours after previous application but just before next application
Project Humber: h7-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,760, as supplied.
Modified Draize Repeated Insult Patch Te>.t Study in Human Subjects
Table 1 (continued)
0X>a Number
O 76
77 78
t) 0
79
80
o
X
81
oe
Ul
82
n 83
84
85
D 86 r> 87
m 88
'o 89
> na
90 91
z r<
92 93
> 2
94
> <5
95
0 96
97 a 98
99 2 100
24 48
24 48
24 48
24 48
Initial Exposure 24 48 24 48 24 48
24 48
24 48
0 24 48
Chailenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 l> 0 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00
0c
00 00
00 00 00 00 0n 0G 00 0n 0u 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00
00 00 00 00 00 00 00 00 o0 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00
00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
e
24 Reading 24 hours after application 48 " Reading 48 hours after previous application but just before next application
Page 7 of 9
*08
Page 8 of 9
0 IO S E A R C H . IN C O R P O R A T E !-* P O B O * 8 5 9 8 P H IL A D E L P H IA . P E N N S Y L V A N IA 1910 ( 2 1 J D 3 9 - 4 4 9 9
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,760, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
Subject mber
101 102 103
1 24 48
00 00 00
23^* 24 48 24 48 24 48
00 00 00
00 00 00
00 00 00
Initial Exposure
56789 24 48 24 48 24 48 24 48
00 00 00
00 00 00
00 00 00
00 00 00
24 48
00 00 00
10 24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00
00 00 00
00 00 00
24 * Reading 24 hours after application 48 * Reading 48 hours after previous application but just before next application
******
9IO S E A R C H IN C O R P O R A T E L I
Project Number: 87-5670H fc.l. du Poni de Nemouis 6, (Juiuputiy , lue. - 10,/OU, uh sappii-d. Modified Draize Repeated Insult Patch lest Study in Human Subjects
Summary of Table 1
Initial Exposure
123456789
10
Readings 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48
103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103
Challenge
Original Virgin
Site
Site
24 48
24 48
103 103 103 103
.
PO 0 0 X 8 5 9 6
P H IL A D E L P H IA . P E N N S Y L V A N IA 19101 .
Page 9 of 9
12151739
24 * Reading 24 hours after application 48 " Reading 48 hours after previous application but just before next application
GRADING SCALE Human Patch Test Studies
Reading
1+ 2+ 3+ 4+
Interprtt Ion
negative suspicious slight erythema well defined erythema erythema with induration erythema with ulceration
DEFINITIONS*
Sensitization is a phenomenon which manifests itself by local efft.-8 on either skin or mucous membranes. It differs from primary irritation in . a t it may also involve tissues remote from the site of application. These r e a s o n s represent an allergy to a chemical which is not obtained on first conta:.. 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 ,.o uce primary irritation may elicit severe skin reactions after a n u m ^ r of exposures. Nevertheless, these reactions may not be considered incidc ts o 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 ern reactions have been called "skin fatique". This latter term is a that it does not imply a condition in which the skin has lost sl^--icant 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: Associa, ion of Food and Drug Officials of the United States.
N f)0*
BIOSEARCH i INCORPORATED - P.0. BOX 8598 - PHILADELPHIA. PENNSYLVANIA 19101 - (215) 7't-U99
BIOSBARCH INCORPORATED
Hi
/// //////\\\
////// ///
/// \\\///
P.O. Box 8598, Philadelphia. Penneylvanla 19101 Telephone: (215) 739-4499
Project Number: TeatIng Facility:
87-5670H
Bloaearch Incorporated 3408-50 "B" Street Philadelphia, PA 19134
Sponsor :
E.I. du Pont de Nemours & Company, Haskell Laboratories P.O. Box 50, Elkton Road Newark, DE 19714
Ine.
Test Article:
16,761
Test Article Description:
Blue fabric
Tf'iL Article Received: 05/14/87
Study Initiated:
05/27/87
Study Completed: 07/02/87
Date of Report : Test : Ob 1ect of Test : Method of Test :
07/06/87
Modified Draize Repeated Insult Patch Test Study in Human Subjects
To determine the irritating, fatiguing and sensltizing 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 Cosmetics" 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 103 volunteer Cauca sian subjects. These subjects were all determined to be in generally good health, 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.
Project Number:
87-S670H
Page 2 of 9
E.I. du Pont de Nemours 6 Company, Inc. - 16,761
Modified Dralze Repeated Insult Patch Test Study In Human Subjects
Method of Test; (continued)
'
Results:
Approximately a one inch square portion of test article was applied to the appropriate skin site and covered with 2" Dermicel hypo-allergenic cloth tape (Johnson a Johnson, New Brunswick, N.J. 06903). The patch remained in place for 24 hours.
At the er.: of this period, the patch was temoved and
the site -as examined for any dermal response. Scor
ing of irritation was in accordance with the scale in
the Appencix. The subjects were then rested for a 24
hour per: i/d after which the skin site was again
examined. A patch was then applied to the same site
as previcisly used.
The second application was
identical :o the first and remained in place 24 hours.
This procedure was repeated on alternate days until a
series or ten applications had been made. The same
site continued to be used throughout the study period
as long as no irritation or only minimal irritation
(1+) was >een after each 24 hour rest period. If
greater irritation (2+ or more) was noted then the
subject '-as either rested or the contact site was
changed a: the discretion of the investigator.
Approximately a 2 to 3 week rest period then elapsed
after w h i m a challenge application wus applied in the
same manner and to the same sites described above. A
duplicate hallenge application was also applied in
the same manner to a virgin site (previously
untreated on the other arm.
-The challenge
applicatic- was removed after 24 hours and the sites
were exanined for signs of irritation or
sensitizat:o n Follow up examinations were conducted
at 48 hours after the challenge application.
The subjec-.s involved in this study ranged in age from 16 Lo 68 y-:ars of age.
See accompanying table, summary and apperdix.
BIOSEARCH I INCORPORATED - P.0. BO) 5 9 B - PHILADELPHIAi PENNSYLVANIA 19101 - (215) 739-4499
Project Number.
87-5670H
Page 3 of 9
E.I. du Pont de Nemours & Company, Inc. - 16,761
Modified Draize Repeated Insult Patch Test Study In Human Subjects
' From the results obtained in this study as described above with the particular group of subjects tested, the test article is moBt likely not a primary skin irritant. The test article is most likely not a iatiguing agent. The test article is most likely not a sensitizing agent.
Submitted by Biosearch, Incorporated:
Raymo M e d 1cal Director
Karl L. Gabriel, V.M.D., Ph.D. President
BIOSEARCH. INCORPORATED - P.0. BOX 8598 - PHILADELPHIA. PENNSYLVANIA 19101 - (215) 739-4*99
Project Number: 87-5670H E.I. du Pont de Nemours & Company, Inc. - 16,761, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
m 6in
| Table 1 ni
z Initial Exposure
0X Subject > Number
1 24 48
2 24 48
3 24 48
4 24 48
5 24 48
6 24 48
7 24 48
8 24 48
9 24 48
o
1
2
u3 04 oX 5 ain 6
CD 7
8
9 X 10
Orr
11 12
T) 13
14 Xm 15
z 16 -r< 17
> 18
> 19 (0 20
00 00 00 00 00 00
00
00 00
00
00 00 00
00 00 00 00
00 00 00
00 00
00 00
00
n0
00
00 00
00
00 00
00 00 00 00 00
00 00 00
00 00 00 00 00
00
00 00 00
00
00 00 00
00 00 00 00
00 00 00
00 00 00 00 00
t) 0
00
00 00
00
00 00
00 00 00 00 00
00 00 00
00 00 00 00 00 11 0
00 00 00 00 00 00
00 00 00 00 00
00 00 00
00 00 00 00 00 00
00 00 00 00 00 00
00 00 00 00 00
00 00 00
00 00 00 00 00
0 (1
00 00 00 00 00 00
00 00 00 00 00
00 00 00
00
00
00
00
00
0u
00
00
c0 00
00
00
00 00 00 00 00
00
00
00
00 00 00 00
00
00
00 00
00 00 00
00
00 00 00 00 0
00 00 00
21 0 0 0 0 0 0 0
22
00
00
00
0
23 N ? 24 NU(Jl0 25 &
00 00 00
00 00 00
00 00 00
0 0 0
<0
24 " Reading 24 hours after application
0 0 0 0 0
00 00 00 00 00
00 00 00 00 00
00 00 00 00 00
00
0c
00
00
00
00 00 00 00 00
48 " Reading 48 hours after previous application but just before next application
10 24 48
Challenge
Original Virgin
Site 24 48
Site 24 48
00 00 00 00 00
00 00
00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00
00 00 00 00 00
00 00
00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
00 00 00 00
00
00 00
00 00
00
00 00 00 00 00 00
00 00 00 00 00 00 00 00 00
Page 4 of 9
S,
M
Cottt*tn
B IO S E A R C H . IN C O R P O R A TE D
P O B O X 8 5 9 8 P H IL A D E L P H IA . P E N N S Y L V A N IA 19101 12151 7 3 P - 3 9
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,761, an supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
Subject Number
26 27 28 2V 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
1 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
2 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 n0 00
3 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
4 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Initial Exposure
567 24 48 24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 o0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
9 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
10
24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 0c 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 " Reading 24 !hours alter appiicat ion 48 Reading 48 hours after previous application but just before next ,application
Page 5 of 9
*4 not
B IO S E A R C H IN C O R P O R A T E D P O B O X 8 5 a 8 P H IL A D E L P H IA . P E N N S Y L V A N IA '9 <01
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,761, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
Subject Number
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
Initial Exposure
1 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
2 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
3 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
4 24
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
5 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
6 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
7 24 48
00 00 00 00 n0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
8 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
9 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
10 24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
24 Reading 24 hours after application m ding 48 hours after previous application but just before next application
Page 6 of 9
739 4499
Wt}
__ "A "W
Project Number : 87-567UH
F.I. du Pont de Nemours & Company, Tnc. - 16,761, as supplied.
Modified Draize Repeated Insult Patch Test Study in Human Subjects
Table 1 (continued)
0a Subject 0Ta Number
moH 76
77 78
0D 79 80
0X 81 a> 82 - iii
84
85
D
T
86
rCn>
87 88
Tl T
89
90
m 91
i
U<)
r
92 93
>7 94
> <05
95 96
97 98
99
100
1 24 48
2 24 48
3 24 48
4 24 48
Initial Exposure
567 24 48 24 48 24 48
8 24 48
9 24 48
10 24 48
Chailenge
Original Virgin
Site
Site
24 48 24 48
00
00
00
00
00 00 00 II o 00 00 00
00
00 00 00 00 00 00
00
00
00
00 00 00 00
00 00
00
00
00 00 0n 1) II 00
00
00 00
00 00 00 00 00 00
00
00
00
00 00 00 00
00
00
00
00
00 00 00 (1 11 u0 00 00
00
00 00 00 00 00 00
00
00
00 00 00 u0 00
00
00
00 00 00 00 00 <1 (I 00 00 00
00
00 00 00 00 00 00
00
00
00 00 0n 0u 00
00
00
00 00 00 00 00 I) 1) 00 00
00
00
00 00 00 00 00
00
00
00
00 00 0n 0u 00
00
00
00 00
00 00 00 <) 11
uu 00
00 00 00 00 00 00 00
00
00
00
00
00 00 u0 0n
00
00
00 00 00 00 00 (1 II 0u 00 00 00 00 00 00 00 00
00
00
00
00
00 00 0u 00
00
00
00
00
00 00 0n
fl u
00 00 00 00 00 00 00 00 00 00
00
00
00 00 00 u0 00
00
00
00 00 00
00 n0
no
u0
00
00
00 00 00 00 00 00
00
00
00
00
00 00 0u 00
00
00
00
00
00
00 00
II u
00
00
00
00 00 00 00 00 00 00 00 00
00 00 00 00 00
00
00
00
00
00 00 00
II (I
00
00
00
00 00 00 00 00 00 00
00
00
00
00 00 00 00
00
00
00
00
00
00
00
II II
00 00 00
00 00 00 00 00 00 00 00 00 00 00
00 00 00
24 - Reading 24 hours after application 48 - Reading 48 hours after previous application but just before next application
Page 7 of 9
e
Page 8 of 9
B IO S E A R C H IN C O R P O R A T E D P O BO X 8 5 9 8 P H IL A D E L P H IA . P E N N S Y L V A N IA 19101 < 2 1 5 ) 7 3 9 4 4 9 9
Project Number: 87-5670H
E.I. du Pont de Nemours & Company, Inc. - 16,761, as supplied.
Modified Draize Repeated Insult Patch Test Gtudy in Human Subjects
Table 1 (continued)
Subject Number
101 102 103
1 24 48
0 0 00
Initial Exposure
2345678 24 48 24 48 24 48 24 48 24 48 24 48
00 00 00
00 00 00
00 00 00
00 00 00
00 00 00
00 00 00
9 24 48
00 00 00
24 48
00 00 00
10 24 48
Challenge
Original Virgin
Site
Site
24 48 24 48
00 00 00
00 00 00
00 00 00
24 " Reading 24 hours after application 48 * Reading 48 hours after previous application but just before next application
*
t Niimh*r : R7 -r>*70H
E.I. du Pont de Nemours & Company, Inc. - 16,761, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects
sn i z n oao Os> moh Readings
Summary of Table 1
12
24 48 24 48
3
24 48
4
24 48
Initial Exposure
56 7
24 48 24 48 24 48
8 24 48
103 103 103 103 103 103 103 103 103 103 103 103 103 103 103 103
0
I
5om
i P t*zn0 zir<>zn<
24 - Reading 24 hours after application
.. ,,
5 48 - Reading 48 hours after previous application but just before next application
not
C B/
Page 9 of 9
Modified Dralze Repeated Insult Patch Test Study In Human Subjects
GRADING SCALE Human Patch Test Studies
'ad1ng
0 + 1+ 2+ 3+ 4+
Interpretation
negative suspicious slight erythema well defined erythema erythema with induration erythema with ulceration
DEFINITIONS*
Sensitization 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 elicit severe skin reactions after a number of exposures. Nevertheless, these reactions may notbe considered incidents of sensitization since after 1 0 - U days of rest the skin recovers its original resistance to injury by the substance. For the lack of a better term sue reactions have been called "skin fatique". 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*
* Dralze, J.H. 1959. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In DERMAL TOXICITY, p.*6-53. Topeka, Kansas: Association of Food and Drug Officials of the United States.
BlOSEARCHi INCORPORATED - P.0. BOX 8598 - PHILADELPHIA! PENNSYLVANIA 19101 * 1215) 739-4499
