Document VJ0ZpEwErK7av3yyGa46N188N
Experiment No.: ('-onductedAt: Dates Conducted: 1--onducted BY:
Reviewed By:
Primary Skin Irritation Test with T-3421
in Albino Rabbits
0863EB0288
Safety Evaluation Laboratory Riker Laboratories, Inc. St. Paul, Minnesota
June 15, 1983 to June 16, 1963 r
23
D. M. Markoe, Jr., BS
Date
Toxi co logi s t
Study Director
K. D. O'Malley, B'@ Senior Toxicologist Acute Toxicology
Date
fbbens, BS
Date
Supervisor, Toxicology Testing
dc: M. W. C. McCormick
Suir,mary The results of the primary skin irritation test conducted from
June 15, l9B3 to June 118, 198- at Riker Laboratories, Inc., St. Paul,
Minnesota indicate that T-3421 is moderately irritating (3.2/8.0) to the
E;kin of female albino rabbits.
Mild
erythera and edema were noted at
!:.heone hour evaluation following a one day occluded contact period. The (?rythema persisted at the 48 hour evaluation while the edema subsided
:31ightly.
introduction The objective of this study was to determine the primary skin
irritation potential of T-3421 to the skin of female albino rabbits. Thi s study was conducted in accordance with the Food and Drug Administration's Good Laboratory Practice Regulation of 1978. Tne raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives.
2.
Mt!,.hc>dand Results Young albino
rabbits
of the New
Zealand
breed a were
used in the evaluation
cJ-the primary skin irritating properties of the test article. b
procedure was modeled after that of Draize et al
The test
One day prior to the application of the test article, the hair was clipped
from the back and flanks of each rabbit and two test sites selected lateral to
t.liemidline of the back approximately ten centimeters apart. One of the two sites was abraded by making four epidermal incisions, two perpendicular to the
other two, while the other test site remained intact. The test article (0.5 g) was applied to each of the test sites on each
rabbit and immediately covered with two-inch square gauze patches. The patches, ,.hich were placed directly over the test sites, were secured with gauze wrap.
7,he trunk of each animal was then wrapped with impervious plastic sheetingcwhich held the patches in position during the one day exposure period.
At the end of one day, the plastic wrappings, patches, and all residual -d
t.est article were removect--. One hour and 48 hours after removal of the test z-irt4@clet,he intact and abraded test sites were examined and scored separately
J@or erythema and edema on a graded scale of 0 - 4. The average irritation produced was evaluated by adding the mean scores for
t@rythema and edema of the intact test sites one and 48 hours post removal of the test article. Similarly, the mean scores for erythema and edema of the abraded test sites were added.
a ---H-azleton b - DiCaize:
Dutchland, Inc., Denver, PA Appraisal of the Safety of Cheziicals in
(1965).
.c10 x 12 x .002 Extra Clear polyethylene sleeves,
Wheeling, Illinois. d The test article was removed with acetone.
Foc>ds, Drugs and Cosmetics PPC Industries, Inc.,
3.
T',-iestewo values were totaled and divided by four to obtain the mean primary ir-ritat.ionindex. The scoring criteria for ery--hema and edema are shown below.
Scoring Criteria for Skin Reactions
Reaction
Description
Score
Erythema Edema
Barely perceptible
1
(Edges of area not defined
Pale red in color and area definable 2
Definite red in color and area well 3
defined.
Beet or crimson red in color
4
Barely perceptible
1
(Edges of area not defined)
Area definable but not raised more
2
than 1 mm.
Area well defined and raised
3
approximately 1 mm.
Area raised more than 1 mm.
4
Maximum Primary Irritation Score
8
The following grading system was used to arrive at a descriptive primary
@;kinirritation rating:
Mean Pr@-mary Irritation Score (Range of Values)
Descriptive Rating
0 0.1 - 0.5 0.6 - 1.5 1.6 - 3.0 3.1 - 5.0 5.1 - 6.5 6.6 - 8.0
Non-irritating Minimally Irritating Slightly Irritating Mildly Irritating moderately Irritating Severely Irritating Extremely Irritating
The rating for a test article may be increased if the reactions caused
are beyond simple erythet.-oand edema, e.g. necrosis, escharosis, hemorrhage.'
The results are presented in Table 1. The protocol, principal personnel
involved in the study, composition characteristics and Quality Assurance
statement are contained in Appendices I - IV.
Animal Number 3B987 3B990 3B993 3B996 3B951 3B991
I'able 1 Primary Skin Irritation Test
with T-3421
Albino Rabbits
Irritation Scores for Abraded
Skin Sites after Removal:
1 Flour
Er.
Ed.
48 Hours
Er.
Ed.
2
2
2
1
2
2
2
1
2
1
1
0
2
2
1
1
2
2
2
1
2
2
2
1
Irritation Scores for Inta
Skin Sites after Removal
1 Hour
48 Hour
Er. -- Ed.-
Er.
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
Mean Subtotal
2.0
1.8
1.7
0.8
6.3
Rating- Moderately irritating
I)rimaryIrritation index: 3.2/8.0
Key: Er. = Erythema Ed. = Edema
2.0
2.0
1.8
0
6.6
Acute Primary Skin IrritatioTnest TEST: -
SPONSOR:
3M
Co.Tj-.ercial Chemica!
0663EB0288 APPEINDIX I Riker Experiment No.:
PROTOCOL
CONDU(:TED BY-. Safety Evaluation Laboratory, Riker Laboratories, Inc.,St. Paul, Minnesota
TEST ARTICLE:
CONTR(:)L ARTICLE:
PROPOSED
STARTINGFICOMPLETION
[)ATE OF TEST:
TEST SYSTEM: Female New Zealarvd WMe Albino Rabbits
SOURCE:
Division
OBJECTIVE:
To determine the irritatiopnotentialof the test arlicleto the skin of
6 animals. Rabbits were
selected as the test system due to their historicaluse, sensitivittyo irritantse,ase of handling and
general availability.
METHOD:
The animals willbe housed in standard wire-mesh cages intemperature and humidity controlledrooms
with tood@ and water offered ad libitum.Each animal willbe assigned a numbered ear tag, which will
correspond to a card affixedto the outside of the cage. Priortothe applicationof the test articlet,he hair
willbe clipped from the back and flanks of each animal and
2
test sitesselected lateral
to the midline of the back approximately ten centimeters aparl. 1
of the 7
siteswillbe abraded
by making four epidermal incisions,two perpendicular to the other two, while the other testsite(s)will
remain intact.The test article( 0 q g -rq,;n
willbe applied to 1
abraded and
intactsite(s)an each animal, covered with
P
and secured with
.
The trunk of each animal willthen be wrapped with impervious plasticsheeting which willocclilri6the
test articled,,@rintghe 1 day exposure peric>d.One hour and 48 hours afterremoval of the test article,
the intactand abraded test siteswillbe examined and scored separately for erythema and edema on a
graded scale of 0 to 4-b.The average irritatiopnroduced willbe evaluated by adding the mean scores
for erythema and edema of the intacttest sitesone and 48 hours post removal of the test article.Simi-
larly,the mean scores forerythema and edema of the abraded test siteswillbe added. These two
values willbe totaled and divided by four to obtain the mean primary irritatioinndex and then assigned
a descriptiveprimary skin irritatiornatingas follows:
Mean Primary lrhtationScore
Descriptive Rating
0
Non-irritating
0.1 -0.5
Minimally Irritating
0.6-1.5 1.6-3.0 3.1-5.0
SlightlyIrritating
4'
Mildly Irritating
i
Moderately Irritating
4
5.1-6.5
Severely lr6tating
6.6-8.0
Extremely Irritating
The rating for a test articlemay t>e increased ifthe reaction caused is beyond erythema and edema and are deemed to be of importance in the interpretationof the results.All raw data generated by the study directorand the finalreport willbe stored in the Riker Lat>oratories'Archive, St. Paul, Minnesota.
A Puhna Rabbit Chow, Ralston Purina Co., St.Louis, Missouri Draize: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics (1965) Pub4rt* by the Edito ICommittee of the Associationof Food and Drug Officialosf the United States.
W. C. MCCOrMlCK Sc>or.sor
6-9-83 Date
eol Study Direc!or
Date
6.
APPENDIX II Pri.ncipal Paz-ticip-ating Personnel Involved in t@he @tudy
Name D. M. Markoe, Jr., RS
K. Y.. Ebbens, BS
K. 0. O'Malley, BS
G.
Pecore
Function
Toxicologist Study Director
Supervisor Toxicology Testing
Senior Toxicologist Acute Toxicology
Supervisor Animal Lat)oratory
7. APPENDIX III
Test and/or Control Article Characterization
f . i<
1. The identity st-rength, unifor-mity, composition, purity or other pertinent chalxacterizations of the test and/or control substances ve
been deter-m@.ned and documented as of
a
t 2. The method of synthesis or origin of the test and control subs ances,
including their amount and the method of bioassay (if applicable) is
doclimented.
yes lxno
3. The stability of the test and/or control substances have been determined or will be determined as of
The above information cords.
and documentation
are located in the sponsor's re-
Spo.@isor
5 S-I-E3
Date
3 IDV46 40 ISS3 )94!9) 3
pr-e-==II\i\ol8IEEiIDID
JLI@4133
L
APPENDIX IV QUALITY ASSU@ZANCE STATEMF-NT Acute Toxicolc>qy Laboratory Studies study No.:
This short ter-m study was audi-ted by Compliance Audi,. and the final report exazl@-ned against the raw data on The results of the audi-t were reported to the study director and to management on
in add4-ti-on to the data audit, different s4-gn@-ficant phases for studi-es under-way in the Acute Tloxicology laboratory are @-nspecl@ed weekly on a recurring cycle, and the facil4-ties are exami,-)ed by Compliance Aud@-t on a three month scnedule.
Compliance Audit Date