PDF - Cosmetic Ingredient Review

Transcription

Personal Care
Products Council
Committed to Safety,
ua ity nnovation
Memorandum
TO:
F. Alan Andersen, Ph.D.
Director COSMETIC INGREDIENT REVIEW (CW)
-
FROM:
John Bailey, Ph.D.
Industry Liaison to the CW Expert Panel
DATE:
June 15, 2011
SUBJECT:
Clinical Data: Products Containing Ethylhexylglycerin
Consumer Product Testing Co. 2008. Repeated insult patch test of a liquid eyeliner containing 0.5%
Ethylhexylglycenn.
Orentreich Research Corporation. 2005. Predictive patch test study (600 panel) of a facial cream
containing 0.4975% Ethylhexylglycerin.
Product Investigations, Inc. 2007. Determination of the irritating and sensitizing propensities of a
foundation containing 0.4% Ethylhexylglycerin.
Product Investigations, Inc. 2008. Determination of the irritating and sensitizing propensities of an
other makeup prepartion containing 0.995% Ethylhexylglycerin.
Clinical Research Laboratories, Inc. 2008. Repeated insult patch test of a fragranced body lotion
containing 0.6965% Ethylhexylglycerin.
1101 17th Street, N.W, Suite 30O Washington, D.C. 20036-4702
202.331.1770
202.331.1969 (fax)
www.personalcarecouncil.org
Consumer Product Testing Co.
FINAL REPORT
CLIENT:
ATTENTION
TEST;
Repeated insult Patch Test
ProtocolNo.: 101
TI ST MATERIAL:
Liquid Eye Uner
c.r)
0.
E
—
k/C
‘jl h
1
EXPERIMENT
REFERENCE NUMBER:
Richard R, Eisenbarg, MJ5.
Board Certified Dermatologist
Jo ‘r
R.N.
Executive Vice President, Clinical Evaluations
,
This rprt i subriufled fo The a
name ol theac Laboraicriea nr
wilhut wrlln athopza1on.
1)
_\c
1)[fltJ1 Llp’
•
luia use il ie per5vci, parlneshp, t urportan tn whown is sddrsssad ;,ri -iiFIiei trc epurt i li
any rnaribe1 ol s stall, reay ‘e ucc ri rneCtrnn Th Pte
or eale ci any prOdu(t or process
I-jjrtjtkt
J(iSt’. I 171)04- 5 1 4
•
I)7i tMl)--7 j I I
•
II\ (!l;.I
t— T2 14
Consumer Product Testing Co.
QUALITY ASSIJRM CE UNiT STATEMENT
Study No.
The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of clinical
laboratory studies, These studies have been performed with adherence to the applicable JCI-I Guideline
E6 for Good Clinical Practice and requirements provided for in 21 CFR parts 50 and 56 and in
accordance to standard operating procedures and applicable protocols. The QAU maintains copies of
study protocols and standard operating procedures and has inspected this study. All data pertinent to
this study will be stored in the Consumer Product I cstrng Company arehie, unless specified otherwise.
in writing by the Sponsor.
Quality Assurance personnel involved:
Quality Assurance
ate
1 he representatne signature ol the Quality Assurance Unit signifies that this stuth has been performed
in accordance with standard operating pro edures arid study protocol as well as government regulations
regarding such procedures and protocols.
J
cw D iluh I .u ic
(
•
Riirliekl, Nv ki.s(’v (171 )t)4-2 I3
i97;i 1 ii-7 I I I
it •
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htu
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I i I97: i )s72: 14
Objective:
To determine by repetitive epidermal contact the potential of a test material
to induce primary or cumulative irritation and/or allergic contact
sensitization.
Participants:
One hundred fifteen (115) qualified subjects, male and female, ranging in age
from 16 to 79 years, were selected for this evaluation. One hundred three
(103) subjects completed this study. The remaining subjects discontinued
their participation for various reasons, none of which were related to the
application of the test material.
Inclusion Criteria:
a.
b.
c.
d.
e.
Exclusion Criteria:
a.
b.
c.
d.
Male and female subjects. age I 6a and over.
Absence of any visible skin disease which might be confused with a skin
reaction from the test material.
Prohibition of use of topical or systemic steroids and/or antihistaniines
for at least seven days prior to study initiation.
Completion of a Medical History form and the understanding and
signing of an Informed Consent form.
Considered reliable and capable of following directions.
111 health.
Under a doctor’s care or taking medication(s) which could influence the
outcome of the study.
Females who are pregnant or nursing.
A history of adverse reactions to cosmetics or other personal care
products.
Test Material:
Liquid Eye L
Study Schedult
Panel 4
awith parental or guardian consent
Initiation Date
Completion Date
.!ebruary 25, 2008
February 27, 2008
April 4, 2008
April 10,2008
Methodology:
The upper back between the scapulae served as the treatment area.
Approximately 0.2 g of the test material, or an amount sufficient to cover the
contact surface, was applied to the 1 x l’ absorbent pad portion of a clear
adhesive dressing. This was then applied to the appropriate treatment site to
form a semi-occlusive patch.
Induction Phase:
Patches were applied three (3) times per week (e.g., Monday, Wednesday,
and Friday) for a total of nine (9) applications. The site was marked to
ensure the continuity of patch application. Following supervised removal
and scoring of the first Induction patch, participants were instructed to
remove all subsequent induction patches at home! twenty-ibur hours after
application. The evaluation of this site was made again just prior to re
application. If a participant was unable to report for an assigned test day, one
(1) makeup day was permitted. This day was added to the Induction period.
With the exception of the first supervised Induction Patch reading, if any test
site exhibited a moderate (2-level) reaction during the Induction Phase.
application was moved to an adjacent area. Applications were discontinued
for the remainder of this test phase, if a moderate (2-level) reaction was
observed on this new test site. Applications would also be discontinued if
marked (3-level) or severe (4-level) reactivity was noted.
Rest periods consisted of twenty-four hours following each Tuesday and
Thursday removal, and forty-eight hours following each Saturday removal.
Chailcupe Phase:
Approximately two (2) weeks after the final Induction patch application, a
Challenge patch was applied to a virgin test site adjacent to the original
Induction patch site, following the same procedure described for Induction.
The patch was removed and the site scored at the clinic twenty-four and
seventy-two hours post-application.
Manufaciured by TruMed Technologies, Inc., I3umsville, MN
Evaluation Criteria (Fthema and additional Dermal Seguelac):
0
0.51+
1
2
3
4
No visible skin reaction
Barely perceptible
=
Mild
Moderate
=
Marked
evcre
E
I)
S
P
V
B
U
Sp
=
—
Edema
Dryness
Staining
Papules
Vesieles
Bullac
Ulceration
Spreadina
Erytherna was scored numerically according to this key.
If present,
additional Dermal Sequelac were indicated by the appropriate letter code and
a numerical value for severity.
Results:
The results of each participant are appended (Table 1).
Observations remained negative throughout the test interval.
Subject demographics are presented in Table 2.
Summary:
Under the conditions of this study, test material, Liquid Eye Liner
did not indicate a potential for derrnal irritation or allergic
contact sensitization.
Thble 1
individual Results
Liquid Eye Liner
Virgin Challenge
Sublect
Number
1
2
3
4
5
6
7
8
9
10
11
12
13
1$
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
0
0
0
0
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$
-
S
24*hr
1
2
3
4
_5
Phase---------—-—
6
7
Site
Z4
h
4
r l2hr
—---
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
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
D1[) NOT COMPLE1 E STUDY---------------I)lDNOTCOMPLETESTUDY-----0
0
0
0
0
0
0
0
0
0
0
0
0
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
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
----DiD NOT COMPLETE
0
0
0
0
0
0
0
0
0
0
-
—
0
0
0
0
0
0
0
0
0*
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
STUDY---
Supervised removal of 1 Tnducton and Charlenge PaLch
Observation recorded 96 hours post challenge applieation. Subject unable tc rcport, as scheduled.
Staining
0
0
0
0
0
0
0
0
0
0
Table I
(continued)
Individual Results
Liquid Eye Liner
:Subj ect
Number
31
2
33
34
35
36
37
38
$0
4
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
24
S
=
—
24hr
I
2
o
O
o
0
0
0
0
0
0
0
0
0
o
o
o
o
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
0
0
0
0
0
0
0
0
0
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
——Induction Phase
4
5
6
0
0
0
—--—DiD
o
O
0
O
o
o
0
o
0
0
0
0
0
0
0
0
0
0
0
0
0’
0
0
7
.8
9
Virgin Chalknge
Site
241w 72hr
0
0
0
0
0
0
o
0
0
0
0
0
0
0
0
O
0
0
0
0
0
0
o
0
NOT COMPLETH STUDY
0
0
0
0
0
0
0
0
0
0
0
0
-DID NOT COMPLETE STUDY0
0
0
0
0
0
0
0
DID NOl COMPLETE STUDY----—---—-—
0
0
0
0
0
0
0
o
0
0
0
0
0
0
o
0
o
0
0
0
0
0
o
0
0
0
0
0
0
0
0
O
0
0
0
0
0
0
0
0
0
0
0
0
0
o
0
0
0
0
0
0
0
O
0
0
0
0
0
0
0
o
0
0
0
0
0
0
0
o
0
0
0
0
0
0
0
o
0
0
1)
0
(1
o
0
o
0
0
0
0
0
O
0
O
0
0
0
o
o
0
o
0
0
o
0
0
0
0
o
(I
0
o
o
o
o
0
0
O
0
o
0
0
0
0
o
0
0
o
0
0
0
0
O
0
0
o
o
0
a
0
O
0
ü’
o
O
0
0
O
0
0
o
0
0
0
0
O
0
Supervised removal of I’ Induction and Challengt Patch
Staining
Table 1
(continued)
Tndividuai Results
Liquid Eye Liner
Subject
Number
1
2
3
4
5
6
7
8
9
10
11
13
14
15
16
17
19
20
21
22
23
24
25
26
27
28
29
24
m
-
-------—
24hr
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
-
0
——
I
2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
--—----—--
Induction Phase
4
5
6
Virgin challenge
Site
4*fl 72 hr
—
7
$
9
0
0
0
0
0
0
0
0
0
m
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
()
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
om
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
DID NOT COMPLETE STUDY—-0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
DID NOT COMPLETE STUDY.-----0
0
0
0
0
0
0
0
0
—-—---DLD NOT COMPLETE STUDY
—DiD NOT COMPLETE STUDY------———----DID NOT COMPLETE STUDY
—-—
---—----—
—-—
—
—-—-V--—
Supervised temoaI 01 1 induction and Challenge Patch
Additiohal makeup day granted at the discretion of the clinic supervisor
Stbject not present for super’ised removal
Table I
(continued)
IndMdual Results
Liquid Eye Liner
Subject
Number
I
2
3
—lnducticrn Phase4
5
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
—
24*hr
30
0
0
31
o
o
o
o
o
o
o
o
o
o
o
o
a
32
33
34
35
36
3?
38
39
40
41
42
43
44
45
46
47
$8
49
50
51
52
53
54
()
0
o
o
0
o
0
0
0
55
56
5?
58
24*
=
S
o
0
0
0
o
0
0
0
0
0
0
0
o
0
0
0
0
0
o
0
0
0
0
0
a
o
o
0
0
0
0
0
0
0
0
0
—
0
0
0
7
8
9
0
0
0
0
0
0
0
0
0
0
0
0
O
0
O
0
a
0
O
0
0
0
0
0
0
o
o
o
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
a
o
a
0
0
0
0
0
0
0
0
0
0
0
si
0
0
0
0
0
Os,
0
0
0
0
0
0
0
U
0
0
a
Virgin Challenge
Site
24*hr 72hr
0
0
0
0
o
0
0
a
0
0
0
0
o
0
o
a
0
0
0
0
0
0
0
0
NOT COMPLETE STUDY
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
O
0
0
Supcrvised remov1 01 1nducion and Challenge Patch
Addiiion& makeup day granted at he discretion of the cIinc upcrvisor
Staining
0
0
0
0
0
0
0
0
0
0
0
0
O
0
0
0
0
0
0
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
O
O
0
O
0
0
0
0
0
0
0
0
0
0
0
0
Table 2
Panel
Sub ivc. Data
Subject
Number
I
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Initials
SB
SL
AD
iF
ED
EB
MA
DB
OP
AF
BF
SB
CO
RC
OF
CR
OP
KP
MP
SF
RC
DL
26
LG
RO
LL
PL
27
JC
28
29
JC
SR
25
Ag_
47
39
40
26
55
62
67
24
64
24
36
47
41
30
41
57
28
53
47
56
24
23
58
75
Sex
M
F
M
F
F
F
F
F
F
F
F
F
M
F
F
F
F
M
F
F
M
F
F
M
F
52
49
M
35
7
55
M
M
F
Table 2.
(continued)
Sbject Data
Subject
Number
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
initials
Age
Sex
AS
CB
CN
AP
NO
CI
AB
PC
CW
LC
LC
1P
BC
OS
iF
HB
DC
59
72
66
46
43
49
79
42
46
70
79
62
53
58
70
77
33
48
44
39
22
45
51
29
29
45
44
53
M
M
F
M
F
F
F
F
F
F
M
M
F
F
F
M
F
F
F
M
F
F
F
F
F
M
F
M
RS
OR
3f3
EM
RA
SM
SW
OC
KC
JR
Taf1e 2
(continued)
Subject D
Subject
Number
I
2
3
4
5
6
7
8
9
10
II
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
initials
Age
Sex
CG
ii
MM
AQ
ML
DB
OS
SS
AD
RM
CB
SJ
FC
CD
55
CS
ND
MR
MZ
BM
SW
39
26
31
F
F
F
F
F
F
F
F
F
F
M
F
F’
F
M
F
F
F
F
F
F
F
F
F
M
F
F
F
M
EM
LII
EL
LM
AD
TI)
RU
52
55
46
56
20
35
26
21
27
42
17
60
45
20
39
16
68
56
55
26
60
20
50
67
39
16
Table 2
(continued)
Subject Data
Subject
Jum1
lals
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
4
49
50
51
52
53
54
55
56
57
58
MP
DD
JD
DW
JM
AT
NT
KP
AP
Kfl
AG
JD
NR
MC
MR
NE
JW
RS
NE
DO
MC
RN
SS
ZS
LA
Dlvi
DS
PZ
EL
‘*__
Sex
37
29
36
40
56
61
61
44
55
41
40
59
36
50
73
64
73
57
51
45
49
33
24
66
54
58
54
61
61
F
F
M
F
M
M
F
F
F
F
F
M
F
F
F
F
F
F
F
M
F
M
M
F
F
F
F
M
F
4
4;
600 PANEL
-
PREDICflVE PATcI-1 TEST STUDY
Facial Crer—
cD
f1 Ic
ORNTREICH RESE
E f-yI /
j
1
II CORPORATION
S.entch,EE
Cathcrinc A. Oi-entreich, M.D.
1 M.D.
Norman Orentrich
September 2005
C-’r
+
600-PANEL
PREDICTIVE PATCH TEST STUDY
PURPOSE:
The purpose of this study was to determine the primary irritation, skin fatiguing and allergic
eczematous contact dermatitis sensitizing potential of the following product on human subjects.
Facial Crear
MATE[tL4L:
The test material was supplied by
METHOD:
A total of600 subjects completed the patch test study following a modified maize technique
(Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, Association of Food and
Drug Officials of the U.S., Austin, Texas, 1959, p.52) of repeated insult predictive patch testing.
The modified maize technique wassuppiernenledwith an additional challenge application one week
after the 11th application- The patch tests were performed as follows:
The subject’s entire upper back was thoroughly cleansed with 70% isopropyl alcohol. The
material to be tested was impregnated into a one-half inch square gauze pad with an occlusive
hacking.
The patches were applied to the previously cleansed skin site and covered with
DERMICEL adhesive tape (Johnson & Johnson, New Bn.nswick, New Jersey) and allowed to
remain in contact with the skin for 4S hours. On removal of
patches, the skin site was observed
for signs of an immediate reaction. One to two hours later, before the next patch was applied, the
skin site was examined for a delayed reaction. This sequence was repeated 10 times. After a twoweek interval, patches were reapplied for 48 hours (first challenge) and the skin site observed for
immediate and delayed reaction. A second 48-hour challenge application was made one week after
the first challenge and the skin site again observed for immediate and delayed reaction. A total of
12 applications of the test material were made.
The test applications were applied during the following time periods during 2005.
FIRST
TENTH
FIRST
SECOND
NO.
APPLlCTION
APPLICATION
CHALLENGE
CHAlLENGE
1
July 14
August 1
August 15
August23
156 30()
July 15
August 2
August 16
August 24
301 456
-
August 3
August 21
September 6
September 14
457 600
August 4
August 22
September 7
September 15
SUBJECT
-
155
The patch test readings were recorded as follows:
No Reaction
0
O5-
MinimalErythema
LO-
MikI&ythema
2O
Moderate Erythema and Edema
3.0
4.0
-
-
-
Marked Erythema, Edema and Vesiculation
Severe ETythenia and J3ullous Reaction
RESULTS:
It is our considered opinion that the results of the 12 application patch test study on
600 subjects showed no evidence ofprimary irritation, skin fatiguing, or allergic eczematous
contact dermatitis sensitizing potential. (See attached charts for individual test results.)
HUMAN $KN SENSITIZATION STUDY - RESPONSE
MATEa1AL FACIAL CREAM
-Volatilize
EXPOSURES
SUBJECTS
1
2
3
4
5
6
1
8
9_
10
W.
E.
ET.
H.
L.
P
.N
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
NA
0
0
a
a
o
a
a
0
C)
0
0
0
0
0
0
0
0
0
C
a
0
0
0
0
0
S.
6
0
0
0
0
C
0
0
0
0
0
0
0
0
a
o
a
a
a
a
a
a
L.
0.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
6
0
C
ii,. N.
12FM,
13,M. M.
14,D0
i$i. K.
6
0
0
0
0
0
0
0
0
C
0,
0
a
a
a
0
0
0
0
0
0
a
a
a
a
a
a
o
o
0
0
I8R.
17,L.
18R.
19D.
C.
S.
F.
L
0
a
0
0
0
a
0
0
0
a
0
a
NA
a
0
0
a
a
20,E,
I.
a
0
a
21A, M
22.C0.
23,P. A.
24,C
0.
r,
0
0
0
0
a
0
0
0
0
a
0
I
2
3
4
..
6
T
7
A.
&
0
O.
iop.
.
0
0
0
a
a
a
0
0
1?12
0
0
0
0
0
0
0
0
0
0
0
0
a
a
a
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
a
0
0
0
a
a
a
a
a
0
a
a
a
a
0
0
0
0
0
0
0
0
0
0
0
o
o
a
0
a
a
a
0
a
C)
a
a
a
a
a
a
a
a
a
0
0
0
0
0
0
0
0
a
a
a
a
a
a
a
a
a
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
6
6
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C)
0
0
0
0
0
0. N Recton
0.5 Minimal Eryihama
to- Mrd Eyierna
2Q Modeiate Etytllama d Edema
10 Maited Erytherna, Edern and VeeicuMion
40. Severe Erythema and Bu11ois Reacon
0
NA
Test rnateraI exposed for 48 hours
Two Weeks after last posze
One week after Ffrst ChM1ene
NA. Not Available for visit
HUMAN SKIN SENSITIZATION STUDY RESPONSE
-
4
MATERIAL: FACIAL CREAM
Volatilize
EXPGSURES*
SUBJECTS
1
2
3
4
5
6
7
8
9
0
11
i2
26,A,
C.
27.J.
C.
28,S,M.
29.H.
N.
30.7
N.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
31R.V.
32. S,K.
33.F. C
C.
34.C.
35J,
P.
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
C
0
0
0
0
0
0
0
0
0
0
0
0
0
36.J,M
37,E. M.
F.
38.D.
39,1,C,
40.P. C.
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
NA
NA
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
.L.
42,E.
4.N.
P.
C.
F
N
F
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
o
o
o
0
0
0
0
0
0
0
0
0
0
0
0
0
0
D.
P.
0
0
o
V.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
C
C
0
0
0
0
0
0
0
0
0
0
0
0
o
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
41
45G.
4,L.
47.A
48,N.
49.G.
,R.
E.
N.
0- No Reac1tor
Er1tema
0.5
tO Mfld Efythema
20- MQdat Erythema ad Edema
Vesku4ion
3,0 Marked Erytherra, Edema
4.0 Severe Er4hma and BuI[ous ReacOn
-
0
0
0
0
0
0
0
0
0
0
0
*Tost niateiiai exposed for 48 bows
Two Week* after last eq,osure
O,e week alter FrI Challenge
NA Not Avaflabe for st
HUMAN SKIN SEN SITIZA1,.
4
MATERIAL; FACIAL CREAM
SUBJECTS
-VoIatIIIze
EXPOSURES*
1
2
3
4
58
7
8
9
10
5IH. S.
52.J.C,
3.P.G.
54K.
B.
55.J.
M.
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
a
a
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
a
a
0
0
0
0
0
o
a
a
a
a
a
a
5.E,
57.B.
PA.
H.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
M.
E.
0
0
0
0
0
0
58.E.
0
0
0
0
0
E.G.
61
2J F,
63,3,
C.
64.A.
V.
55.P.
F.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
56.A.
67.C.
V.
C.
0
0
0
0
0
0
0
0
0
0
68.E. H.
&9,M,C.
70.0. C.
0
0
0
0
0
0.0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
C
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
71 .8.
72.0.
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
a
0
a
0
0
0
0
0
0
0
0
a
0
0
59.P.
60A.
V.
C.
W.
0
73Mp4,
0
0
74,K.
G.
0
75.T,G,
0
0
0
0
0
0
0
0
0
0
0
0- No Reaction
05- MnImaJ Erythema
10-hd Eryhema
oer8te Erhema and Edema
2.0
3.0 Marked Erytheia, Edema and VescuIaon
4.0- Seiiere E%ytherna nd Bvtous Reaction
-
0
0
0
0
0
0
0
0
0
0
0
1?’
0
0
0
0
Test male1& exposed k 46 hot*s
Two Weeks after last exposre
One week after Frst ttiauenge
MA No4 Aaiile for vsit
“
-
0
0
0
Q
0
a
0
0
HUMAN SKIN SENSfTIZATION STUDY RESPONSE
-
4
SUBJECTS
[
-Vo!atIflze
EXPOSURES
i1**i2
1
2
3
4
5
6
7
8
9
10
76,C.
R.
77F. A.
78J.
C,
79K.T
80E, B,
a
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
81
A.
2D,
8A.
84S.
85M.
M.
M.
K.
C.
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
C
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
8&A.
88,M,
$9R.
g0,L.
A.
C.
G.
F.
F
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
1.F.
92L.
93N.
S.
P.
T,
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
8?R.
G
95D.
96,
97B,
A.
90
99
8.
100
.1.
•EV
B.
B
T,
M
M.
M.
0- No Reaction
Q5 Minimal Eryther
tO Mild Eyterna
20. Moderate Fiythema and dem
Marked Eythema. Edema and Vcutalon
4.0- Severe Erytlema and Li1louS Reactlor
-
0
0
Tet material epoed for 48 hours
Two Weeks after last exposure
Cr* week aft Ffrt Chaltenge
NA Not A0able for vi511
-
0
0
0
0
0
0
0
0
0
0
HUMAN SKIN SENS1TZATION STUDY RESPONSE
-
MATERIAL: FACIAl. CREAM
SUBJECTS
Volatilize
EXPOSURES’
1
2
3
4
5
8
7
8
9
10
i1
i2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
C)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1Q
P.
102
J.
103.R.
104H.
105.J.
0,
V.
Z.
C.
106.F.
101,A.
IOBD.
IGOB.
i1Q$.
H.
Z.
S.
M.
5.
0
0
0
0
IliR,
112P.
113J,
114.B.
115,A.
S
R.
C.
M.
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
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
116N.
P.
117.F,
118.G.V.
11,8.
H.
12CR
C.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
121D.D.
i22Q,
M
123,X.M.
124.B,.
1255.
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
NA
0
0
0
0
43
0
0
0
0
0
0
0
0
0
0
0
0
0
0
,
0
.
0
0
0
0
Reaction
04- Minimal E%ytherfla
10.tldEry?en,a
20 MxIeraIe Erythema and Edema
3.0 Marked Erytlenia Edeiia Rnd VescuIatlvn
4.0 Severe Etythia and 8ulPoas Revton
-
-
0
0
0
0
0
iest rnatedaP exposed tor 48 ho4Jr
Two W.eks after last expeiJre
One week after First Ciai1enge
NA Not Aveilable for visit
“
-
HUMAN SKIN SENSITIZATION STUDY - RESPONSE
MATERIAL FACIAL CREAM
-VoIatdze
EXPOSURES*
SUBJECTS
1
2
3
4
5
6
7
B
9
10
11
L.
M.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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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20 Moderate tbema and Edema
3,0 Masl<ed Eythem EdemB and Veu11ion
40 Severe rmema 1 Bulkius Reacton
-
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0
0
0
0
o
Tes( mafeia1 expc$ed foi 48 Iouis
TwQ Weeks alWr as epose
One weeI after Firs* Ca11nge
NA Nat Avabki f v4&t
-
MATERiAL.: FACIAL CREAM
EXPOSURE$*
SUBJECTS
5
7
B
0
0
0
0
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0
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0
NA
0
0
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0
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Moderate zythera ajd edema
Marked Etytherna, Edema and Veecuation
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10
11
12
0
0
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0
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0
0
0
0
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0
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T, Weeks after It exposure
One week after First Cha1erige
NA Not Aaie for vL&il
-
HUMAN SKIN SENSITIZATION STUt)Y RESPONSE
MATERIAL: IACLAL CRE
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—
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2
3
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0
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328.A,
329T.
330R.
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0
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4.0 Sev.te Erythama and Aullous Re.eeffon
-
Tesl material BxpO5ed fw 48 hOr$
*fr
One week after FIr!t C[enge
NA Not AvallIe k,r €sit
-
0
4
-VolatIlize
EXPOSURES*
SUBJECTS
1
2
4
5
6
7
8
3
10
1112
0
0
0
0
0
0
0
0
U
0
0
0
0
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T
est rnateraI exposed br 48 bours
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NA Not AaIiabte br 1sit
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MATERLL: FACIAL CREAM Vo(atillze
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SUBJECTS
2
3
4
5
8
7
8
9
10
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40 Sevece Eiythema nd 8ulous Reaci}on
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T Weeks after last exposure
One week after First Cbaflenge
NA Not Ayabe fc v
-
0
HUMAN SKIN SENSITIZATION STUDY RESPC)NSE
-
EXPOSURES*
SUBJECTS
1
2
3
4
5
6
7
89
10
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2.0- Mode’ate Eiythema and Edema
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-
-
Test material exposed or 46 hours
Two Weeks after iast epost*re
One ek after I9rst Challenge
NA Not Available r vtslt
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a
MATEiIAL: FACIAL
SURJECTS
I-Volatilize
EXPGSURES
t
2
3
4
5
—
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0
0
0
0
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0
0
0
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0
0
0
0
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0
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0
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0
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0
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0
0
0
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0
0
0
0
0
0
0
0
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0
0
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0
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0
0
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o No Rpaciion
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10-Mild Eythema
2.0 Moder3te hema and dma
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4.0 Sere EiyThema and Buikus Reactto,
-
-
0
0
NA
Te1 maEeiai exposed fx 4 hoirs
two Weeks after bst eposwe
One week arter First Chaflenge
NA Not AvdIe br visit
-
-Volatilize
EXPOSURES*
SUBJECTS
0
10
11
2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
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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
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7
1
2
3
4
5
4510,
L.
452,R P.
453W.P,
454S
P.
455, P
0
0
0
0
0
0
0
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0
0
0
0
0
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0
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NA
NA
0
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0
0
0
0
0
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455,0, C.
457.E.
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0
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0
0
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0
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0
0
0
0
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0
0
0
0
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0
0
Test material exposed br 4 bours
Two Weeks after Issi exposure
‘Qne week alter First Ctia*ere
NA- NotAvalla4eforvlsit
0
0
-
EXPOSURES
SUBJECTS
1
2
3
4
5
6
7
80
10
1V
12
M.
C.
G
M.
W.
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
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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a
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8.
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0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
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0
0
0
Q
0
0
0
0
0
0
4860.
487,F.
488,J,
409.R,
490L.
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0
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0
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
0
0
0
0
0
0
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0
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0
0
0
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0
0
0
0
0
0
L.
491.A.
492.L, C.
493.T,
L.
494.B
L
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0
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0
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0
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0
0
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U
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499.J
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0
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0
0
0
0
0
0
0
0
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0. No Reac1on
0.0 Miin’ai Eiytherna
1.0 d Etytherna
2.0- Moderal Erytheina and Edema
3.0 Marked ryhenia, Edema and Vesiculation
40 Seveie Eythei,a and flulkxis Reato
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Test materia’ exposed fOr 48 o&s
Two Weeks after laSt exposure
One week after First ChaHen
NA Not AaiIable (ocst
0
0
-
A
MATERIAL: FACIAL CRE
EXPOSURES’
SUBJECTS
1
2
C.
F.
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0
0
0
0
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0
0
4
5
5
7
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
10
11
0
0
0
0
0
0
0
0
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0
0
0
0
0
0
0
0
0
0
0
0
0
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0
0
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0
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0
0
0
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0
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0
0
0
0
0
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0
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0
0
0
0
0
0
0
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0
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0
0
0
0
0
0
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0
0
0
0
0
0
0
0
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0
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0
0
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0
0
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0
0
0
0
0
0
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0
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0
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NA
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0
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0
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516E.
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0
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2,0 Mderte Erythem ad Edema
-
3.0 Ms1Ød Eiytherna, Edema and VescvfaJon
4.0 Se’ere Erythema ød uus Rwtkn
-
Test matera expod for 48 flours
The Weeks atier ast ecpasure
One ee)c after First Chaere
NA No Avaabie for
-
—
MAIERIAL: FACIAL CREAM
EXPOSURES*
SUBJECTS
—
26.C.
527.M.
528,B.
529.T.
530,i
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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
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
5
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
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
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
546,.
547.1.
548,Y.
549.A.
550,A,
M.
G.
5.
V.
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0
0
0
0
0
0
0
0
0
0
0
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1.0 Md cyhem
2.0 Mociratø Erythema and Edwa
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4.0 Swero .r’1henia and Buk 1eac1io
-
10
3
V.
V
ft.
-
9
2
543.P,
544.A,
545.0.
S..
542.1.8.
7
1
0
0
0
0
0
541,J.
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Volaiflize
-
—
0
Te5t material exposed (or 4 hrr
Two Weeks after bst exposure
Or*wee aftet PirstCha1en9e
NA Not Ava1abe for vIsit
12
0
MATERIAL FACIAL. CREAM
SUBJECTS
Volatilize
EXPOSURES
I
2
3
4
5
6
7
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
M.
0.
0
3
0
0
0
0
0
0
.J.
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559.L. 0.
GE. 0.
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
561,J
562.A.
563.M.
564.L.
565.t
M.
C.
R.
B.
1.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
566.A.
T.
551
568M.
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S.
S.
M.
N.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
571.P- C,
572. B
573.k-t. M,
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0
0
0
0
0
0
0
0
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0
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0
0
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—
51.W.
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554.
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F.
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.
0
-
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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
NA
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
0
a
a
a
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0
0
0
0
0
0
0
0
0
0
0
0
1)
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
-
1.0
20
3.04.0-
9
0
0
0
0
0
O No Rac*ion
-
0
0
8
—
Pmai Erythema
Mld Erytheia
derate rythema arwl Edema
Maed ExylPema, Eczema arid VesicLdatlon
Severe Er1heme and &louS Readian
0
0
7estmateriai expOsed fo 48 hours
rno Weeks alter last expQs.r
NA
One week after First Challenge
tot Avaable br vilt
-
HUMAN SKIN SENSZATLON STUDY - RESPONSE
MATR1A: FACIAL. CREAM
Volatilize
EXPOSURES*
SUBJECTS
1
2
3
4
5
6
7
9
10
1I
i2
0
576A.
577.1.
578J,
579.E
580,E.
W.
R.
F.
D
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0
0
0
0
0
0
9
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
NA
0
0
0
9
C
0
0
0
0
0
0
0
9
0
0
ci
0
581.M,
K.
5.
S.
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0
0
0
0
0
0
0
0
0
0
0
0
ci
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
9
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
0
0
0
ci
0
0
0
0
0
0
0
9
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
ci
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
ci
0
0
0
0
0
ci
0
ci
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NA
0
0
0
0
0
0
0
C
0
0
0
0
0
0
0
0
0
0
0
0
ci
0
0
0
0
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0
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583D,
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585TC.
586V.
557,Y.
588,M.
6890.
590,8.
8..
V.
D,
591P.
892,A,
8
T.
595
594,J.
J,
5,
0.
0
ci
0
0
0
596,A,
697S.
5,L.
599V.
60CF.
tI
0.
8.
0.
D.
ci
9
0
0
0
.
B.
o
No Rec1ic
Mhilmal Lythema
1.0 MIE4 thema
2,0 Mderaq Erythnma arid
30 Made4 Erytheme Cdema and
4,0 Severe Eiytherna and Bvloijs eavto
40 Sevete E*ema and BIos Reacton
-
-
Test matea1 aposed for 48 iois
Two W0ek5 after !st expoeute
One week attei FIriCtge
NA Not AIab4e for visit
ci
PRODUCT IWVESTIGATIONS. INC
1 5 Fai Tth AvflL
Crnshoho(ken PA 1942S
(ijQ-&25-5855 lax 6I(J-825-728.
PS
PS
RfPORT
A?41) SENSITIZING PROPENSiTIES OF
HUMAN SKIN
d:c’
.9%
PREPARED 10K
25 May zoir,
C
i/Ce’
Tjo[CoNTENm
1.00
Objectives
2.00
Design
100
Spomor
4.00
Sloth Product
500
Site of Study
6.00
Dates of Study
7.00
Selection of SubJects
Page 1
Page 2
Mi Recruiting
—
02 informed Consent
.03 Determination of Eligibility
.04 Panel Infurmaton
8.00
Site information
9.00
Patching De4 ices
10.00
D*ta Acquisition
11.00
Overview of Study Regimen
12.00
Study Reginien
Week
4)
Page 3
Page 4
Reglnlen
Week #2 Regimen
Week #3 Regioien
Week #4 Regimen
Page 5
Week #5 Regimen
Weeks #6 and 7 Regimen
13.00
Procedure Devistions
14.00
Compliance
15.00
IncIdence of Responses
16.00
SIgnificance of the Responses
17.00
Condusion.s
18 00
C ompLIanc Wslh (rood
Page 6
Q % Standards
44
___________________c
___________
______
DITERMINAnoN OF rOF
.00
1A’fiNC .-.ND SENSITIZING PROPENSITIES
HUMAN SKIN
OBJECrWES
.01 To tdentifv and chamctcrize the skin-damaging propensaics that
an be induced to crcise
un&r the conditions of this modi lied patch tc.s t procedure.
02 To adudgc whether the exercise ofwh propensities under the patch test condiiions contraindicates the kind
ot’skin contact that would be occasioned during the ppropriatc use of the product.
2.00
DESIGN:
.01 A modified version of the Repeated insuft Patch Tes
was L iduded under
double blind condiiions on a pant composed of more
ouisei
02 The regimen comprised nine sequcncial 24-hour induction applications and tw cnncurrcntly conducted 24hour ch.t1knc applications one on the rnti1 indutuin site and one on a naiv i1e
03 IJuruig the tinodi phe th. skm ol th. contact .ite5 wac graded and the grades rcorded on Wednesdays
Fridays (i.e. twenty-four houn after patches had been removed), and Mondays (i.e. foiy-eight hours afler
patches had been removed).
.04 During thechallenge phase. the skin olthecontact sites was graded within moments after the patches had bcvn
removed and again twenty-four and forty-eight hours later. Follow-up examinations were conducted thereafter
only if adverse effrcts were present.
.05 This study was conducted in comphance with the standards of good clinical practices generally applicable for
the protection of the privile es and we
g of indivIduals who par(
“test procedures.
-
3.00
SPONSOR:
Project Director:
Authorization:
4,00
5.00
STUQJ’RODUCT:
SITE OF
Study Personnel:
6.00
DATES OF STUDY:
Type of Product:
Sponsor Identification:
Date received:
Quantity rcc’d:
Form used in study:
H N
Lotion
I 323!O7
>
600 g. gross
WI
neat
Product investigations, Inc.
151 East Tenth Avenue
Conshohocken, PA 19428
Medical Director:
Dir. Derm. Studies:
Technicians:
Quality Atsuranec:
Moms V. Shcianski, MDCM
Joseph F. Nicholson Ill
Margarc Reilly. Kay Walk
Samuel J Chrlcs Ill
Started:
Completed:
26 March 2007
27 April 2007
Page 1
7M11
$JLLCT1ON OF SUHJECtS:
.01 RICRUITING:
Prospcctive sub
ects were recruited from surrounding tecalirics via phone. pucr and personal ejntact,
3
.02 INFORMED CONSENT:
All individuals who expressed irnerest in par1icipatin were given an informed content document to rcad. This
document, which cach candidate had to read and sign betbre being entered into the srudy, presented the
Ibilowing ink imation
a. 1-tow many subjects were to be enrolled in the study:
b The intended use of the product;
c. Why the product was being restcd
d. how the test was to be perfomied;
c. Thar the regimen was not intended to benefit a subject’s health, well bcin, or quaiity of life.
f. The diffetniways that participation may be detrimental toasubjeci’s health, welt being, orqualiiy of tile,
g. That nor all detrimental effects could be foreseen and made known at tbc time the inlbrmed consent was
presented for the prospective subject’s sgnanire.
h. What commitments a subject had to make to be in eomplincc; and
I. What considerations a subject was entitled to receive and the condiLkoils for receiving them.
.03 DEIRMtrrigz OF ELIGiBILITY:
lntItrmation concerning a prospective subject’s qualifications was obtained from the answers the subject gave
in tilling out a medical history form and in responding to specific quesLions. Those who did not meet the
following criteria were rejected.
a. Inclusion Criteria: Satisfaction of all the follow lug itenis was obligatory:
i. The candidate was at least eighteen years old, and
ii. agreed to comply fully with the schedt1ed study regimen, and
iii. expressed awareness that a participant would incur risks that would affect herhis well-being, and
iv, denied that the amount of ibe stipend had induced hei/him t participate against her/his better
judgement, and
v. had rend the informed consent agreement. and
vi. had assared the interviewer that she/he had no questions about thc informed consent’s contents tb-at h3cl
nor been answered to her/his satisfaction, and
vii.had signed the consent form willingly and without reservation.
b ExIuson (riteria Any one of the 1oLloi ng ItemS was cause for relection
i. The candidate had an illiest that contraindicated participation; or
ii, a condition that rendered the skin unsuitable for use in this study; or
iii was using dosages of medications that could alter the skin’s tolerance: or
iv had a documented histnry of rntoleranLe t the catcgor of products submitted for tudv or
v. was a female who was pregnant or was breast feeding an infani
.1)4 PNta. FoRMATlON:
a.
Panel NC:
b. Denioraphks:
SES
irnb.r
ss
4i
C.
Dedication:
Ac R.gic
j
J
It
ni
3J
The subjects in this panel were engaged coricomitaiilly in the studies of
by sponsors other than
products
submitted
8,00
SITE INFORMATION
.01 LOCATION:
wt
assigned 3and
I on rhe upper left arm on each subject,
Sm:
At each vistt the skin around the contact sire was marked to facilitate examinations after the device was
removed and positioning of subsequently-applied devices as precisely as was feasible on the same site.
.02 IJfNTJFICATION OF A CONTACT
Page 2
900
rcHJNC DFViç
.111 i’VPIOF DEvICE:
PadiaHy-occiusive pauhing devices consistingofi 2 cmx 2cm absorbent pad centered on thdhesive-voated
surfaue of a 2 cm x 4 cm plastic film were used to ci,mvcv and matittain rho product on the skin.
.02
PREPA5pNØF A P4TcHIrG Di:
a. The wehnl pad of a patching device was evenly coared with approximately () mg. of the test material,
.03
POSITION1.SNB REMOV1N
.
P4TCIHC Dvict:
a. A prepared devicc was positioned on its designated site on each subject with the product-treated ‘uriacc
of the pad in contact with the sktri.
h. Firm presLie was applied to the hacking of the device to eflct intimate contuci of the pad with the skin
and to bond the flanges of the device securely to the skm.
c. When the time conic ftr removing the device, the device was peeled ofT the skin as gently a’ was tasihle
under the circumstances,
10.00
DATA ACOUlSlTj:
.01 (PlNG PaocFDU:
a. Pxaminauons of the contact sires to grade the eficcis elicited by the product were conducted on MaiWays.
Wednesday and Fridays. When a subject came in on a scheduled examination day, the teclmiciim examined
the skin of the contact site.
i. If no adverse cffect was detected, a IY’ was recorded in the subjeef’s Case Report Fomi.
ii. If an adverse effect was detected, the technician entered a grade indicating her assessment of the
response’s intelisily.
b. ‘rhe ‘uhjcct was then sent into the patching mom where the site was examined again by a second technician
to ascertain independently whether or not the site should be used again. If she disagreed with the first
technidan’s assessment, the application was held in abeyance until the issue could be resolved with the
hclp of the supervisor and.’or the investigator
e. The supervisor or the investigator was called in not only when a disagreement had to be resolved but
also
to validate substantial sudden chancs, eg. when a rpotise is deemed to merit a grade 3 or when
a
response has been judged to have decreased by two or more points from the previous day’s status
.OZ (flIThRtA FÜR (RAnl RESPONSE lNTEiiSrry:
The following scale was used in this procedure to designate the intensities of those gross skin changes that
may he occasioned by exposing the surface of the skin to a product.
Mrpjo
Subclinical Sta?e
iJtiJ*rnm*tiun
Vascular Dibtiun:
rnfdtratiot
None
0
Faint redness with poorly defined margins
Redness with well-de fined marjns
Redness plus well-defined edema
Redness plus papuks oresicletlccratmon
3
4
.04 S rnCHGJ:
Switch to a Naive She:
If the product had elicited a Grade 2 respotlse on a subject. application of the product was switched
immediately to a naive 51C on the subject
5. DisconIlnutiou of Appikatlons:
i. If the product had elicited a second Grade 2 on a subject, application of
the product was discontinued
immediately tir the remainder of the initial phase on the affected subject.
ii. If the product had elicited a Grade response on a subject, application of the product was discontinued
immediately for the remainder of the initial phase on the affected subject.
i.
Page 3
11.09
OvERvww OF STbPY RLGIMFN:
4od.ay
w.Ø,
4p1
W
t.
uridAp,i
Wed, .3
C.J%pp4
Wed
4.rde
WwI.
12.00
J
J
J
ppI
ta,diy
WdntJy
frd.a
vt
Rf.Appiy
ll
Rn.t
ur4y
S,nd.s
Rtr4ppi
5n
°“‘
4R..od1
-
.r-AppI
em
—
trApp)
—
—
-
lid
4.rdt
Gr,,di”
—
tide’
—
-
STUDY RECIMI:
.01 IcrrIAIJINnucr1aN PlIA
Yk#1:
Miwday:
As cach subject presented hersctf/hinisclf at the clinic. the skin of the contact site assigned to
the product
submitted for study was exasnined and ascertained Il be xuiab1e before applications were begun.
ii. A frcsWyprepared patching device was applied on its assigned site,
iii The skin around the device was marked and the subject was iaistwcted to return ott Tuesday.
Tuesdty:
i, As each subject rcttmcd, the sue-identifying marks were reinforced.
ii.. The patching device was removed by a technician and the subject was instnictcd to
return on Wednesday
Wednesday
i. As each subject returned, the skin of the contact sue was graded. The grade was recorded.
ii.. A ti-eshIyprcpared patching device was applied on the same site.
iii. ‘the site-identifying marks were reinforced and the subject was mstnicted to return on thursday
Thursday:
1. As each subject returned, the sitc-identtfying marks were reinforced.
ii.. [be patching dvive was removed by a technician and the subject was instructed
to return on Friday.
Friday
L
As eat:h subject returned, the skin of the contact site was graded. The grade was recorded.
A freshly-prepared parching device was apphed ott the same site.
ii l’he site-identifying marks were reinforced.
v, The subject was dismissed with Instructions to remove
the patching device trn Saturday. to record the time
of removal and to return to the clinic on the tollowing Monday for resumption olihe regimen.
Wetkt*2 I Weçk #3:
Monday:
i
ii..
ii.
iv
At each subject returned, the skin of the contact site was graded. [hc grade was recorded
‘l’he time at which the patch was removed oq Saturday was recorded
A fi-eshly-prepared patching device wa applied on the same she,
The site-i&iaitvrng marks were reinforced and the subject was instructed to iitum on Tuesday,
Tuesday, Wednesday, Thursday Friday:
The proce.dures Followed were the same as those tbllowcd on corresponding days during Week
1.
Week #4:
Monday:
i.
As each suhjcel returned, the skin of the contact site was graded. The grade wa’ recorded
ii..
The time at which the patch was removed on
lurday was recorded,
iii. a) lfthesuhject had undcsgoneall nine induction appicuIions. sheAw was dimisscd a±er being instructed
as tNiows:
i) to report hack to the clinic on the tbtlowistg Monday to receive the challenge applications, and
ii) to nonfy the iiwestigntor wiihot dhiy should any signiticant changes occur in the
.kin t’the contact sitc before
Misnda of the challenge week,
hI If the subject had not received the required number of induction applications and was deFicient without valid
reason, applications were csniimicd. As many as two uiisaed applications could be made up during
this week.
When the subject had undergone the required number of make tap applications. shhc wa dismissed after being
instructed as in Section a) ii, ahov.
Page 4
+112 iIIxivlMAKk Ui’ PHSE
Week
After the
amination on Monday of Week 4. nLi procedures were scheduled during this period.
+03 HLNGE PHASE
Week #5:
Monday:
As each subject returned, the skm n1du nitiaJ induction site was seniincd and a ertaiitedto be free of
any c ndiüorts that would have rendered it unfit for undcroing the challenge applications.
A prepared devee was applied on the initial induction site,
ii A second prepare.d device was applied on a naive site.
Tht skin around both devices was marked and the sttbjeci was intwcted to remm on Tuesday,
i’ueday:
(Now: If a subject was absent on Monday, shehe was patched on Tuesday.)
t As each subject returned, the site-identifying marks around both contact sites were reinforced,
ii. Both patching devices were removed by a technician,
iii The skin of both contact sites was gradecL the grades were recorded.
i The subject was mstructed to return on Wednesday.
We1nesday:
As each subject returned, the skin of both cOntact sites was graded; the gradcs were recorded.
L If foI1owup was indicated, the subject was zstruc.tcd to return on Thursday, otherwise the subject was
dismissed from the study o1ths materiaL
i.
.
A14 FQLI+Ow-vp PIIAsE
Week No. 6and Week No7:
During the two weeks following the exit examination, the subjects were given the opportunity to relay any
information concerning effects that were relevant to the characterization ol the product as well as
to
communicate the need for tieatrncnt of persistent or newly-occurring responses.
13+00
PROCEDURE DEVIAJIONS:
None were necessary.
14.00
1PLlANCF:
+‘it
Ot tt
PNAE
UY%IPIIANI
axc’l sFT
yt;s
—-
tnduciin
5
0
Ci,iIcngr
141’ c’1L5 Lt19 S.shji
H ‘fit 115 SLijxLs
t
ii
IC?
—
iIiwi jt1i Oie nu
ip]i with th
rrfq
io
—-
dpac
4
n1nairm,
cumnLl*a
:1qrii
yd thuii toIlw.
Page 5
___—
1SM0
INC WENC F RESPONSES
Grn
T’P t R5rusi
La4cijns
riisr
Orl1nl Cinqw Sftr
øyiibkdiinp
10 ibjç
I
Fitt redness, un
uwt5 border
0
“
0
Z
Inte.e rednei. defined berder
0
-
0
i
trdr
+
detIn1e &nta
RIne.i
+
oicite. cr vrsklcs. ctc.
of Recp4rri
‘(oDat cqu,rvd
16.00
0
Nakr Cnti Sue
105
0
0
“
0
ii
0
0 abJeets
Oubjects
I subjeel
4iibjrrts
4 ,ubjer1
-
SIGNIFICANCE OF THE
.01 ltjflAUINDUCTION Pi1sv
No responses were noted on any ofthe I O ubjecis who underwentat least oucpostappticaitort ecaniination.
The absence olrcsponscs charactethe thcproductas one which is devoid ofelinically significanIin-irritating
propcnsitlcs.
.02 CHALLErGE PJ*A$
a.
OrigInal contact Sites:
No responses were noted on any of the 105 subjects who pai-ticipatcd in this phac of the study ilic
tsbscnce of responses characreriie the product as one which is devoid of clinically signiflcarn skhi
seflsitiing propensities.
b.
17.00
Naive Contact Slts
No responses were noted on any of the 105 sihjevts who participated in this phase of ih study. The
absence of responses characteniie the product as one which is devoid cii clinically sgnilici
skin
scnsihrtng propnsi4ics
CONCLUSIONS:
.0
was tciunu o be neither a clinically sigmficam skin irritarn
conditi,iis f this study.
.02
is not contraindicatcd for isagcs entailing repeated :ipplications on human skin under
conditLoas appropriaic for ‘uch products.
PRODUCT iNVST1GATIONS
nor a
%kin scnslttzer under the
INC
Date
IWOO
I have wditcd the iesift presented in this report and beheve that,
reflect the raw data acquired during the course of this study.
to
the best of my knowledge, they accurately
/
/
Samuel Charles
Director. Quality Agurance
,ciPaKe 6
10
0
I:
C
LJ
1W4
C
1*
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0
0
0
0
a
MIT
WEEK 2
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4
INDUCTION PHASE
-
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C 3
C 4
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012
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004
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Subj #
Sponsor Code
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-
MIT
0
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0
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—
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0/0
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8/0
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810
B/U
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8/0 0/0 0/0
— — —
8/00
/00/0
— —
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B/U
0/0
0/0
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8/0
0/0
0/0
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8/0 0/0 0/0
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B/C —
0/0 —
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810 —
010 —
-0/0
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8/0
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WEEK
cHALLENQE WEEK
Site: -Li
—
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046
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054
055
056
057
058
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Sponeor Code:
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0/0
—
—
—
8/0
8/0
—
0/0
010
—
0/0
—
0/0
—
0/0
—
Vo
B/0
8/0
—
810
—
BID
—
B/C
—
0/0
—
0/0
—
—
0/0
0/0
—
0/0
—
0/0
.2&
0/0
—
-—
0/0
0/0 —
0/0 0/0
—
0/0 0/0
— —
0/0 010
—
8/0
BIG
—
B/G
—
8/0
—
-—
010 —
010
010 010
010 010
010 3/0
0/0 010
0/0
0/0
—
—
0/0
0/0
—
—
0/0 0/0
—
0/0 010
0/0 010
010 010
0/0 0/0
— —
A
A
0/0 0/0
—
—
—
—
—
—
,r
-
—
a
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
-—
—
—-—
—
—
—
—
—
—
WEEK 5
—
—
Sita: LI
CHALLENGE WEEK
—
910
B/G
RIO
B/C
8/0
810
—
8/0
—
8/0
—
610
8/0
BiG
810
—
A
8/0
I
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Subj
II:
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
a
--J
-
I
a
0
0
a
0
0
H:,
0
o
o
0
o
0I
o[0
0
0
0
0
0
0
0
0
o
C
0
0
0
0
:0
0
0
0
o
A
I+J
o
M
)
--
F F
INDUCTION PHASE
Ii
[Ii
i
[0
WEEK 3
T I W 1
a
—
—
—
a
1L2
I
a
—
—
LL
—
—
-
—
—
—
—
—
—
—
—
—
0
—
—
—
—
—
-
0
0
—
0
—
0
—
0
—
0
—
0
—
0
—
—
0
0
—
0
—
0
—
0
—
0
—
0
—
I
0
—
I
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
810
B/G
—
8/0
—
010 —
0(0
0/0
0/0
— —
0/0 0(C)
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
a
—
—
—
—
—
—
—
—
—
—
—
BIG 0f0 0/0
610 010
810 010 010
B/U 010 010
810
0/0
6(0
010
0/0
—
— —
A —
A —
A
—
8/0
0/0
0/0
—
—
6/0 0/0 0/0
— —
—
8/0 0/0 0/0
— a
—
8/0
0/0 0/0
— — —
8/00(00(0
—
———
———
— — — —
— —
—
—
—
—
—
—
—
—
—
WEEK 5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
—
—
—
—
—
—
—
WEEK 4
CKALLNGE WEEK
site: Li
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
---
to
—
--
010
0/0
0,0
—
0/0
—
0/0
—
0/0
—
0/0
a
0(0
—
—
---
oio
0/a
—
.22. 22
8/0 —
010
6/0
0/0
— —
B/G
0/0
— —
6/0 —
0/0
—
8/0
0/0
—
—
6/0
0/0
—
—
8/0
0/0
—
—
BIG
0/0
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
———
—
— — — — ————
— — — —
—
—
—
— — — —
0
—
0
—
0
—
2
2
0
T
—
0
a
0
—
0
—
—
—
0
0
—
0
—
0
—
0
—
0
—
0
—
F
0
C)
0
0
0
0
—
0
—
0
—
0
—
0
—
0
—
0
I
HIATUSIMAKEUPS
108
109
104
105
106
107
103
092
093
094
095
096
097
098
099
1 00
101
102
091
Subj N
ft
4
-5-
F
a
M
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
I
—
A
;
‘
TN
Absent
Dropped
—
A
U
I
1
[
I
10
IA
I A
ia
0
io
A
0
0
C
0
0
0
-
71W
0
0
0
0
WEEK 2
F
—
a-
—
—
—
—
— I —
a
0
0
0
0
—
0
0
0
—--
J-—
U
—
a
0
0
0
0
—
--a
-5-—
0
—
LEGEND
-
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
—
—
—
—
—
—
—
—
—
—
a
—
—
0
0
—
—
—
—
-..
—
—
—
—
—
—
a
—
—
—
—
—
—
a
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
8/0
810
—
8/0
—
M
8/0
—
8/0
—
6/0
—
810
—
B/G
—
B/0
—
6/0
—
Sf0
—
8/0
—
810
—
—
-—
a
—
0/0
0/0
—
0/0
—
—
—
0/0
0/0
—
0/0
—
—
—
—
—
a
—
—
—
-—
a
—
—
—
—
—
—
—
—
—
—
—
—
—
—
a
—
—
—
—
—
F
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
U
—
—
—
—
CtALLENGE WEEK
Site: LI
WEEKS
T
W TH
—
0/0
0/0
—
—
—
010 —
0/0
—
(i/O
0/0 —
a
—
010
010
— — —
0/0 -0(0
— —
—
0/0 —
0/0 —
—
-010 —
010
—
—
0/0
0/0
—
—
—
0/0 —
0/0 —
—
010
0/0
—
— —
aio —
0/0 —
010 —
—
810 —
0/0 —
00 —
—
810 —
010 —
0/0 —
—
810 0(0 0/0
—
II
—
—
—
—
F
—
—
— :
—
—
—
e
—
—
—
—
—
a
—
—
—-
—
—
—
—
—
WEEK 4
— —
TW 114
—
—
-
M
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
0
—
—
-5-
0
0
—
0
—
—
0
0
—
0
—
0
—
0
—
0
—
0
—
0
0
0
—
0
—
0
—
0
—
—
-5-
F
Mnday.eekfr Only if any reactions on
the
last Friday week 5 ( challenge weak)
I—
0
INDUCTION PHASE
sponsor vooe
PRO Dua INVESTIGATIONS, INC.
151 East Tenth Avtriue
Conshohocken, PA 19428
6L0-825-5855 fax 6104254288
,..
DETERMINATION OF THE IItRflATING AND SENSITIZING PROPENSITIES
OF
ION HUMAN SKIN
an
Q?Y
rJr
pre
°‘99c°io
PSULAREP FOR
29 February 2008
snlhv/jIyret
TABLE OF CONTENTS
1.00
Objectives
2.00
Design
3.00
Sponsor
4.00
Study Product
5.00
Site of Study
6.00
Dates of Study
7.00
Selection of Subjects
.01 Recruiting
Page 1
Page 2.
14
.02 .Enrornied Consent
.03 DeterminatIon of Eligibility
.04 Panel information
8.00
SIte Inrorination
9.0()
Patching Devices
Page 3
10.00 Data Acquisition
11.00 OvervIew of Study Regimen
Page 4
12.00 Study Regimen
Week #1 Regimen
Week #2 Regimen
Week #3 RegImen
Week #4 Regimen
Page 5
Week #5 Regimen
Weeks #6 and #7 Regimen
13.00 Procedure Deviations
14,00 Compliance
15.00 Incidence of Responses
Page 6
16.00 Significance of the Responses
17,00 ConclusIons
18.00 Compliance with Good QA Standards
“
T
”
T[NG AND SENSITIZING PROPENSITIES
ON HuMAN SKIN
HO
QNECYIYES:
0l To identify and characterize the skin.damaging propensities thai
under the conditions of this modified patch test procedure.
can be induced to exercise
..02 To adjudge whether the exercise of such propensities under the ions contraindicaces the kind of skin
contact that would be occasioned during the appropriate use of the product.
2.00
I1J:
.01 A modified version of the Repeated Insult Patch Test
.02
.03
.04
.05
.00
was condixted tinder
double blind conditions on a panel composed of more than one hundred subjects at the outset.
The regimen comprised nine sequential 24-hour induction applications and two concurrenLly conducted
24-hour challenge applications, one on the initial induction Site and one on a naive site.
During the initial phase, the skin of the contact sites was graded and the grades recorded on Wednesdays,
Fridays (i.e. twenty-four hours after patches bad been removed), and Mondays (i.e. forty-eight hours
after patches bad been removed).
During the challenge phase, the skin of the contact sites was graded within moments after the patches had
been removed and again twenty-four and forty-eight hours later, Follow-up examinations were conducted
ihcrcaftcr only if adverse effects were present.
This study was conducted in compliance with the standards of good clinical practices generally applicable
for the protection of the privileges and well-being of individuals who participate in patch test procedures.
SPONSOR:
Project Director:
Authorlradon:
4.00
1LfRODWT:
Type of Product:
Sponsor !dentifiaatic a:
Date received:
Quantity recd:
Form used in study:
P1 N
5 00
$joJi,nJny
Study Personnel:
6.00
Facial Cream
1/09/08
>685g. gross wE.
I:
Product Invesug,.
142 North Ninth Street
Suitc 16
Modesto, CA 95350
Medical Director:
Dir. Dunn, Services:
Dermatologist:
Technicians:
Quality Assurance:
Started:
Completed:
Morris V. Sbelanski, MVCM
Joseph E. Nicholson Ill
Cinton E. Prescott Jr., Ml)
lisa Cortez, Henry Cortez
Samuel J. Charles 111
14 January 2008
15 February 2008
Parr)
SELECTIONOF1JflJE:
.01 RcuiTwiG;
Prospective subjcct were rccruitcd from surrounding localities via phone, posters and personal contact.
.02 lotn Cosi’r:
7.00
All individuals who expressed interest in participating were given an informed consent document to read.
This document, which cacit candidate had to read and sign be fore being entered into the study, presented
the following information:
a. How many subjects were to be enrolled in the study;
b. The intended use of the product;
c. Why the product was being tested;
d. How the tt was to be performed;
a That the regimen was nat mtendcd to benefit a subject s health well being or quality of bfe
f. The different ways that participation may be detrimental to a subject’s health, well being, or quality
of life.
g. That aol all detrimental 1ket could be forescen and made known at the time the informed consent
was presented for the prospectie subject’s signature.
h. What conimitmerns a subject had to make to be in compliance: and
i, What considerations a subject was entitled to receive and the condkions for receiving them.
.O PETERMINArloN OF ELXGIBILITYt
Information concerning a prospective subject’s qualiflcations was obtained from the answers the subject
gave in filling out a medical history farm and in responding to specific questions. Those who did not
meet the following criteria were rejected.
a. IncLusion Criteria: Satisfaction of all the following itenis was obligatory:
i. The candidate was at least eighteen years old, and
i agreed to comply fully with the scheduled smdy regimen, and
expressed awareness that a participant would incur risks that would affect her/his well-being, and
iv. denied that the amount of the stipend had induced her/him to participate against her/his better
judgment, and
v. had read the informed consent agreement, and
‘i had assured the interviewer that she/he had no questions about the informed consent’s contents that
had not been answered to her/his satisfaction, and
i had signed the consent form willingly and without reservation
b. Exclusion Criteria: Any one of the following iteths was cause far rejection:
i. The candidate had an illness that contraindicated participation; or
i a condition that rendered the skin unsuitable for use in this study; or
was using dosages of medications that could alter the skin’s tolerance; or
iv. had a documented history of intolerance to the category of products submitted for study; or
v was a female who was pregnant or was breast feeding an infant.
.04 P4NEL 1N1flRMA
a. Panel Ne;
I,, Demoraphlcs:
[_!
Fnue
[Mile
c. Dedication:
&OO
Nuznbc
AJ
1W
19-70
31
1 —02
This was a shared panel, i.e the subjects were
materials submitted by sponsors other thani
SITE INFORMATK)N:
I
in the evaluation of
I
iwas assigned Band #2 on the right side of the back of each subject.
.02 H)ENTIFLCATION OL A CONTACT S1TE
At each visit the skin around the contact site was marked to facilitate examinations after the device was
rmved and posstionmg af subsequently applied devzces as precssely as was feastbte on the same stte
Pare 2
9.00
PATCmNG DEVICES:
.01 TEoiDEvlcE
PartiallyoccIusive patching devices consisting of a 2 cm x 2 cm absorbent pad cciitrcd oil the adhcivc
coated surface of a 2 cm x 4 cm plastic film were used to convey and inaiiwniri the produci on the skin.
.02 PREARATTQN OF A PATCHING DEVTCE
a. The webril pad of a patching device was infused with l5Od of the test material.
.03 POSITIoNING AND REMOVING A PATCHiNG DEVICE:
a. A prepared device was positioned on its designated site on each subject with the producHreated
surface of me pad in contact with the skin.
b. Finn pressure was applied to the backing of the device to effect intimate contact of the pad with the
skin and to bond the flanges of the device securely to the skin.
e When the titne came for removing the device, the device was peeled off the skin as gently as was
feasible under the circumstances,
10.00
DTA4c$IrJ.O:
.01
GRADING PROCEDURE:
a. Exaniinations of the contact sites to grade the effects elicited by the product were coductcd on
Mondays Wednesday and Fnday When a subjett came in on a cLhedulcd exammatioti day the
technician examined the skin of the contact site,
L If no adverse cfkct was detected, a ‘LV’ was recorded in the subject’s Case Rcport Form
ii. If an adverse effect wits detected, the technician entered a grade Indicating her assessment of abe
response’s intensity.
b. The subject was then scot into thc patching mom where the site was examined again by a second
technician to escertain independently whether or not the site should be used again. If she disagreed
with the first technician’s assessment, the appUcation was held in abeyance until the issue could be
resolved with the help of the supervisor and/or the investigator.
c. The supervisor or the investigator was called in not only when a disagreement had to be resølved, but
also to validate substantial sudden changes. eg. when a response is deemed to mciii a grade ?3 or when
a response has been judged to have decreased by two or more points from the previous day’s status.
.02 CRITERIA
IG RFPOJSEIN’1tNJ1
The following scale was used in this procedure to designate the intensities of those gross skin changes
that may be occastoried b e’rpostng the surface of the skrn to a product
.04
Marphoogy
Visible Changc
Sithdlnlcal tiiae
None
0
1ipq
Vascular Dilation:
Faint redness with poorly defined margins
1
inflftratlont
Redness plus well-defined edema
Grade
-a
3
SITE CHANGES:
a. Switch to a Naive Slte
L If the product had elicited a Grade 2 response on a subject, application of the product would have
been switched immediately to a naive site on the subject.
b. DIstentinuüon oFApp&ations
1. If the product had tlicited a second Grade 2 on a subject, application of the product would have
been discontinued immediately for the remainder of the initial phase on the affected subject.
I If the product had elicited a Grade 3 response on a subject, application of the product would have
been discontmod mimethately for the remainder of the initial phase on the affected subject
11.00
aEQLtMDYJj:
Maday
W.*e
W# fl
W
RtM
Wcdiirday
GtAp$
ZdAppL
**if
dtAppy
d1a.pb’
Ri,.ci
Gdp
W. l
W5
Twrdy
-
A..(y
-
R.R’Ga
Thiirthiy
Friday
Sd.rd
Re*.
(dWIqpty
XnLud)
Suiiih
GrdWA$
—
-
-
G4ppi
(Røe.
—
-
—
—
12.00
.01 INITL4LID4DUCrION PHASE-
Week #1:
Monday:
i. As each subject presented herself/himself at the clinic, the skin of the curnact site assigned to the
product submitted for study was examined and ascertained to be suitable before applications were
begun.
1. A freshly-prepared patching device was applied on its assigned site.
The skin around the device was marked and the subject was inslructed to return on Tuesday.
Tuesday:
i, As each subject returned, the sitc-identifdng marks were reinforced.
ii. The patching device was removed by a technician and the subject was instrac ted to rekrnl Ott
Wednesday
Wednesday:
i. As each subject tetutned, the skin othc Contact site was graded. The grade was recorded.
i A freshiy.prepared patching device was applied on the same site.
iii. The site-identifying marks were reinforced and the subject was instructed to return on Thursday
Thursday:
i. As each subject returned, the si1e4denrifying marks were reinforced.
ii. The patching device was removed by a technician and the subject was instncted to return on Friday.
Friday:
I As each subject returned, the skin of the contact site was graded. The grade was recorded
I. A freshly-prepared patchin,g device was applied on the same site.
i. The site-identifying marks were reinforced.
i The subject was dismissed with instructions to remove the patching devi on Saturday, to record the
time of removal, and to return to the clinic on the folLowing Monday for resumption of the regimen.
Week #2:
Monday:
i, As each subject returned, the ki of the contact site was graded. The grade was recorded.
1. The time at which the patch was removed on Saturday was recorded.
I A freshly-prepared patching device was applied on the same site,
iv The sitcidcntifying marks were reinforced and the subject was instructed to return on Tuesday.
-
Tuesday, Wednesday, Thursday, Friday:
The procedures followed were the same as those followed on corresponding days during Week 1.
Weèk3:
Monday:
I As each subject returned, the skin of the contact site was graded. The grade was recorded,
1. The time at which the patch was removed on Saturday was recorded,
ii A freshly-prepared patching device was applied on the same site,
iv The sitcidenti1ring marks were reinforced and the subject was instrec ted to return on Tuesday.
Tuesday, Wednesday, Thursday, Friday:
The procedures followed were the same as those followed on corresponding days during Week 1.
Week #4:
Monday:
L As each subject returned, the skin of the contact site was graded. The grade was recorded.
i The time at which the patch was removed on Saturday was recorded.
a) If the subject had undergone all pine induction applications, she/he was dismissed afier being
instructed as follows:
i) to report back Co the clinic on the second Monday following to receive thc challenge applications,
and
ii) to notify the investigator without delay should any significant changes occur in the skin of the
contact site before Monday of the challenge week.
b) If the subject had not received the required number of induction applications and was deficient
without valid reason appllcatlon% were continued. As many a two missed applIcations could be
made up during this week. When the subject had undergone the required number of make up
applications, she/he was dismissed after being instructed as in section a) ii, above.
.02
II]ATUS/MAKE
U PHASE..
Week #4:
After the examination on Monday of Week 4, no procedures were scheduled during this period.
.03 CHALLENGE PHASF
Week #5:
Monday:
L As each subject returned, the skin of the initial induction site was examined and ascertained to be free
of any conditions that would have rendered it unfit for undergoing the challenge applications.
K. A prepared device was applied on the initial induction site.
A second prepared device was applied on a naive site.
iv. The skin around both devices was mare4 and the subject was instructed to return on Tuesy.
.
Tuesday:
(Note: If a subject was absent on Monday, the/he was patched on Tuesday.)
i. As each subject returned, the site-identifying marks around both contact sites were reinforced,
1. Both patching devices were removed by a technician.
The skin of both contact sites was graded; the grades were recorded.
.t The subject was instructed to return on Wednesday.
.
Wednesday:
As each subject returned the skin of both contact sites was graded the grades were recorded
i. If follow-up was indicated, the subject was instructed to return on Thursday, otherwise the subject
was dismissed from the study of this material..
.04 FOUOw-ut’ Prrsz:
Week No. 6 and Week No.7:
During the two weeks following the exIt examination, the subjects were given the opporrmiry to relay
any information concerning effects that were relevant to the characterization of the product as well as to
communicate the need for treatment of persistent or newly-occurring responscs
13.00
PROCEDURE DEVIATIONS:
None were necessary.
14.90
COMPLIANCE
NOfAEC’
PSLA.SE
iC ,,fOt lii
iC Df1b I] S.b
:‘
Rcquizrd
EXCUSED
CMPLM
YES
iO
tnthxtron
5
(1
109
2
ChIk
i1
0
109
2
Icwthmn*, 1nqi gç
c ,,jiU,3
lr. copl,uv w,E O
órtr
15.00
INCIDENCE OF RESPONS:
CHALL!s-Pu4sz
GLu
TY or REsOSs
t%1LCnON PHASE
0
No v5Ufl.E CHANGE
1
FAINt REDC4F.SS UNDEFiNED BORDEk
2
lNtNsakEJS,mamiwaolLDsR
3
RED + DEFiNITE EDEMA
4
REDr1$S + AvuiaS. ov VILSICLI’S,
111 SUBJECTS
0
-
ORIGtAL CoTAC7
SITE
109 ECT5
0
4’
AIVII CONTACT SirE
4’
109 suawcrs
0
4’
0
0
0
-
a
0
0
4’
I)
0
4’
0
-
1•:j
16.00
No OF RFSFOYDERS
0 SET5
0 SUBJEcTS
No DATA AcQUIRED
4) SUBJECTS
2 SUBJECTS
2 SuBJECTS
sGANcEA)EmE.REsPoNsEs
01 INmArJINDUCraoN PHASED
No responses wcrc noted on any of the III subjects who underwent at least one post-application
examination. The absence of responses tharacte’rizes the product as one which is devoid of clinically
sigiiiflcant skinirritating propensities.
.02 CHALLENGE P1kAs:
17.00
a.
Original Coittact Sites:
No responses were noted on any of the 109 subjects who participated in this phase of the ,tudy. The
abscncc of responses characterizes the product as one which is devoid of clInically significant skin
sensitizing propensities.
b.
Naive Contact Sites:
No responses were noted on any of the 109 subjects who participated in this phase of the study. The
absence of responses charnctcrizes the product as one which is devoid of clinically significant skin
sensitizing propensities.
CONCLUSIONS
.01
was found to be
conditions of this study.
.02
is not contraindicated, for usages
conditions appropriate for such products.
neither a
clinically significant skin irritant nor a skin sensitizer under the
entailing
repeated applications on human skin under
PRODUCT INVESTIGATIONS, INC.
Date
Dermatologicai Studies
18.00
cQMrLJNCE.rYrnIGOOD QVALITYASSURANCEDARD:
I have audited the results presented in this report and believe that, to the best of my knowledge, they accurately
reflect the raw data acquired during the course of this study.
urance
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—
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Clinical
Research
Laboratories. Inc.
Final Report
Repeated Insult Patch Test
CLIENT:
ATfENT ION:
cD.
TEST MATERIAL:
Frgranced Bouy
i
CRL STUDY NUMBER:
(UNPv’ERSAL)
AUTHORIZED SIGNATURES:
Bruce F. Kanengiser”).
r
President/Medical Di
Michael L41uscatieWo, Ph.D
Exec
—
Jia’Nff
Ceor’J.
urnaié’r, M.D.
Diplomate American Board
of Dcrinilology
REPORT DATE:
371 Hoes Lane
•
April 4, 2008
Piscataway, NJ 08854- (732) 981-1616
•
FAX (732) 981-0520
Clinical
Research
Laboratories, Inc.
Good Clinical PractIce
Quality Assurance Audit Statement
Clinical Study Number: CRL116O8-4
Start Ditc: February 4, 2008
Completion Date: March 14, 2008
The cli:nical study listed above was conducted in accordance with Clinical Research
Laboratories, Inc. Standard Operating Procedures, which incorporate the principles of
Good Clinical Practice defined by applicable guidelines and regulations established by
U.S. Regulatory Agencies. The conduct of the study was monitored for compliance, and
the associated records, including source documents or raw data, were reviewed for
documentation practices and accuracy by a Project Manager/Study Director and/or a
Quality Assurance Representative. Standard Quality Assurance audit procedures for this
and study related documents were conducted, as indicated below.
final
-.
Signature of QA dor
Date
Clinical
Research
Laboratories. Inc.
FINAL REPORT
IEPEATED INSULT PATCH T$T
PURPOSE
The purpose of this study was to determine the dermal irritation and sens:itization
potential of a test materiaL
INVESTICATIVE SITE
Clinical Research Laboratories, Inc.
371 Hoes Lane
Piscataway. New Jersey 08854
732-981-1616
TEST MATERIAL
The following test material was provided by
received by Clinical Research Laboratories, Inc. on January 23, 2008:
The test material was coded with the following CRL identification number:
CR11 1608-4
STUDY DATES
This study was initiated on Februaiy 4, 2008 and was completed on March 14, 2008.
‘Semi-occ1u Strip (FruMcd Tcc
obgi flC.. JumsviIIe, Miirncot)
was
Clinical
Research
Laboratories. Inc.
PANEL SELECTION
Each subject was assigned a permanent CR[. identification number. All subjects signed
an Informed Consent Form in compliance with 21 CFR Part 50: Protection of Human
Subject& and a HIPAA Authorization Form in compliance with 45 CFR Parts 160 and
164. All subjects completed a Subject ProfilelMedical Histoiy Form provided by Clinical
Reseaih Laboratories, Inc. prior to the study (Subject Demographics Appendix I).
Subjects who met the following criteria were impaneled:
-
•
Male and female panelists between the ages of 18 and 70
•
Subjects who have completed a Panelist Profile/Medical History:
•
Subjects who are in general good health as determined by a Panelist Profile/Medical
Histoty;
a
Subjects who do not exhibit any skin diseases that might be confused with a skin
reaction from the test material;
•
Subjects willing to sign an Informed Consent Form in conformance with 21 CFR Part
;
4
50: Prolection of Human Subjects
•
Subjects who have completed a HIPAA Authorization Form in confbrmance with 45
CFR Parts 160 and 164;
•
Females who are not pregnant or lactating;
•
Subjects who demonstrate dependability and intelligence in following directions;
•
Subjects who are not currently using any systemic or topical corlicosteroids ant
inflammatory drugs or antihistamines,
TEST METHOD
Prior to the application of the patch, the test area was wiped with 70% isopropyl alcohol
and allowed to dry. The lest material, which was prepared as described in the Test
Material section of the report, was applied to the upper back (between the scapulae) and
was allowed to remain in direct skin contact for a period of 24 hours
Clinical
Research
Laboratories. Inc.
TEST METHOD (Continued)
Patches were applied to the same site on Monday. Wednesday, and Friday for a (otal of 9
applications during the Induction Period. This schedule may have been modified to allow
for missed visits or holidays. Jf a subject was unable to report on an assigned test date,
the test material was applied on 2 consecutive days during the Induction Phase and/or a
makeup day was added at the end of the Induction Phase.
The sites were graded by a CRL technician for dermal irritation 24 hours after removal of
the patches by the subjects on Tuesday and Thursday and 4 hours after removal of the
patches on Saturday, unless the patching schedule was altered as described above,
The sites were graded according to the following scoring system:
Dermal Scoring Scale
0
1+
21’
3+
4-4-
No visible skin reaction
Barely perceptible erythema
Mild erythema
Well dcfined ezythema
Eiythema and edema
Ervthema and edema with vesiculation
If a 12+tl reaction or greater occurred, the test material was applied to an adjacent virgin
site. If a “2+” reaction or greater occurred on the new site, the subject was not patched
again during the Induction Phase but was challenged on the appropriate day of the study.
At the discretion of the Study Director, patch sites with scores less than a 112+9 may have
been changed.
Following approximately a 2-week rest period, the challenge patches were applied to
previously untreated test sites on the back. After 24 hours, the patches were removed by
a CRL technician and the test sites were evaluated for dermal reactions. The test sites
were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions during (he Challenge
Phase of the study may have been asked to return for a 96-hour reading.
Clinical
Research
Laboratories. Inc.
RESULTS
This study was initiated with 12 subjects. Four subjects discontinued study participation
for reasons unrelated to the test material. A total of 108 subjects completed the study.
Individual dermal scores recorded during the Induction and Challenge Phases appear in
Table I.
CONCLUSION
Based on the test population of 108 subjects and under the conditions of this study, the
did not
test material identified as Fragranced Body Lotion
irritation
or
dermal
potential
for
eliciting
demonstrate a clinically significant
sensitization.
RETENTION
Test materials and all original forns of this study will be retained by Clinical Research
Laboratories [nc. as specified in CRL Standard Operating Procedures 30A3 and 306C
unless designated otherwise by the Sponsor.
-J
a
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•
Clinical
Research
Iaboratories. Inc.
TABLE I
(Continued)
Summary of Dermal Scores
[
1
Test Material: Fraganced Body Li
Challenge_Scares
Induction_Scores
Subject
Number
8
9
Hr1HurHZr
Discontinued
0
0
00
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
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
0
0O_
0
0
0
0
0
0
0
0
0
0
0
00
0
0
0
0
0
0
0
0
0
0
0
0
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
0
0
0
0
0
0
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
6
2
U
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
0
0
0
0
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0
0
0
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0
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0
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0
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0
00
0
0
0
0
0
0
0
0
Clinical
Research
Laboratories. Inc.
TABLE I
(Continued)
Summary of Dermal Seorcs
Test Materi1:
SjCCt
Number
Fragranced Body Lotion
Challenge Scores
1utia_Scores
1
2
3
6
4
7
8
9
-
76
77
78
79
81
82
83
84
85
86
87
88
89
90
91
92
93
9.4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
95
0
96
97
98
0
0
0
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PDF - Cosmetic Ingredient Review

Transcription

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