Document b5jp8yV7xyyMkyrbXwJbja3no
Experim ent No.: Conducted At: D ates Conducted: Conducted By:
Reviewed By:
Primary Skin I r r it a t io n T e st w ith T-3421
in A lbino R abbits
0883EB0288
ARUfe-OatZ
V
%
Safety Evaluation Laboratory
Riker L ab o rato ries, Inc. S t . P aul, M innesota
June 15, 1983 to June 18, 1983
D. M. M arkoe, J r . , BS T oxicologis t Study D irector
i-
Date
v L 1K. D. O' M a lle y , S! Senior T oxico lo gist
Acute Toxicology
Su pervisor, Toxicology T estin g
W. C. McCormick
000137
Summary The r e s u l t s o f the prim ary s k in i r r i t a t i o n t e s t conducted from
June 15, 1983 to June 18, 1983 a t R ik er L a b o ra to rie s, I n c ., S t . P au l, M innesota in d ic a te th a t T-3421 i s m oderately i r r i t a t i n g (3 .2 /8 .0 ) to the sk in o f fem ale a lb in o r a b b i t s . M ild erythem a and edema were noted a t the one hour e v a lu a tio n fo llo w in g a one day occlu ded c o n ta c t p e rio d . The erythem a p e r s is t e d a t th e 48 hour e v a lu a tio n w h ile the edema su b sid e d slig h tly .
1.
In tro d u c tio n The o b je c t iv e o f t h i s stu d y was to d eterm in e th e p rim ary sk in
i r r i t a t i o n p o t e n tia l o f T-3421 to the sk in o f fem ale a lb in o r a b b it s . T h is stu d y was conducted in accordan ce w ith the Food and Drug A d m in istra tio n 's Good L a b o r a to r y P r a c t i c e R e g u la tio n o f 1978. The raw d a t a g e n e ra te d by th e Study D ire c to r and the f i n a l re p o rt a re sto re d in the conducting lab o rato ry 's arch ives.
000138
2.
Method and R e s u lt s
Young a l b i n o r a b b i t s o f th e New Z ealan d b re e d ^ were u sed in th e e v a lu a t io n
of the prim ary skin ir r it a t in g p ro p e rtie s of the t e s t a r t i c l e . p ro c e d u re was m odeled a f t e r t h a t o f D r a iz e je t a l --b .
The t e s t
One day p r i o r to th e a p p l i c a t i o n o f th e t e s t a r t i c l e , th e h a i r was c l i p p e d
from th e back and f l a n k s o f each r a b b i t and two t e s t s i t e s s e l e c t e d l a t e r a l to
th e m id lin e o f th e back a p p r o x im a te ly te n c e n tim e te r s a p a r t . One o f th e two
s i t e s was ab ra d e d by m aking fo u r e p id e r m a l i n c i s i o n s , two p e r p e n d ic u la r to th e
o th e r two, w h ile th e o th e r t e s t s i t e rem ained i n t a c t .
The t e s t a r t i c l e ( 0 .5 g) was a p p lie d to each o f th e t e s t s i t e s on each
r a b b i t and im m e d ia te ly c o v e re d w ith tw o-in ch sq u a r e gau ze p a t c h e s . The p a t c h e s ,
which were p lace d d ir e c t ly over the t e s t s i t e s , were secu red w ith gauze wrap.
The trunk o f each an im al was then wrapped w ith im pervious p l a s t i c s h e e tin g --
which held the p atch e s in p o s itio n durin g the one day exposu re p e rio d .
At the end of one day, the p l a s t i c w rappings, p a tc h e s, and a l l r e s id u a l t e s t a r t i c l e were removed--d . One hour and 48 h o u rs a f t e r rem oval o f th e t e s t
a r t i c l e , the in t a c t and abraded t e s t s i t e s were examined and sco red s e p a r a te ly
f o r erythem a and edema on a grad ed s c a l e o f 0 - 4.
The a v e ra g e i r r i t a t i o n p ro d u ced was e v a lu a te d by a d d in g th e mean s c o r e s f o r
erythem a and edema o f th e i n t a c t t e s t s i t e s one and 48 h ou rs p o s t rem oval o f the
t e s t a r t i c l e . S i m i l a r l y , th e mean s c o r e s f o r erythem a and edema o f th e a b ra d e d
t e s t s i t e s were added.
^aH a z le to n D u tc h lan d , I n c . , D enver, PA
--D r a iz e : A p p r a is a l o f th e S a f e t y o f C h em ic als in F o o d s, D rugs and C o sm e tic s (1965).
--10 x 12 x .0 0 2 E x tr a C le a r p o ly e th y le n e s l e e v e s , PPC I n d u s t r i e s , I n c . , ^W heeling, I l l i n o i s .
--The t e s t a r t i c l e was removed w ith a c e to n e .
000139
3.
T h ese two v a lu e s were t o t a l e d and d iv id e d by fo u r to o b ta in th e mean p rim ary i r r i t a t i o n in d e x . The s c o r i n g c r i t e r i a f o r erythem a and edema a r e shown below .
Scoring C rite ria fo r Skin R eactions
R eaction
D escription
Score
Erythema Edema
Barely p ercep tib le (Edges of area not defin ed P ale red in c o lo r and area d e fin a b le D e fin ite red in c o lo r and are a w ell d e fin e d .
B eet or crim son red in co lo r Barely p erc ep tib le
(Edges of area not defin ed) Area d e f in a b le b u t n o t r a is e d more th an 1 mm.
Area w ell d efin ed and ra ise d a p p r o x im a te ly 1 mm. A rea r a i s e d more th an 1 mm.
1
2 3
4 1
2
3
4
Maximum P rim ary I r r i t a t i o n S c o r e = 8
The fo llo w in g g ra d in g system was used to a r r i v e a t a d e s c r ip t iv e prim ary
skin ir r ita tio n ratin g :
Mean P rim ary I r r i t a t i o n S c o r e ______ (Range o f V a lu e s )_________
D escrip tive 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
N on -irritatin g M inim ally I r r it a t in g Sligh tly Irritatin g M ildly I r r ita tin g
M oderately I r r it a t in g
Severely Ir r ita tin g Extrem ely I r r it a t in g
The r a t i n g f o r a t e s t a r t i c l e may be in c r e a s e d i f th e r e a c t i o n s c a u se d
are_ beyond sim p le erythem a and edema, e . g . n e c r o s i s , e s c h a r o s i s , h em orrh age. '
The r e s u lt s a re p re se n te d in T ab le 1. The p r o to c o l, p r in c ip a l p erso n n el
in volved in the stu d y , com position c h a r a c t e r is t ic s and Q uality A ssurance
statem en t are contained in Appendices I - IV.
000140
Animal Number 3B987 3B990 3B993 3B996 3B951 3B991
Table 1 Primary Skin I r r it a t io n T est
with T-3421
I r r it a t io n Scores fo r Abraded
Skin S i t e s a f t e r Removal:
1 Hour
48 Hours
Er. Ed. Er. Ed.
22 2 1
22 2 1
21 1 0
22 1 1
22
2
1
22 2 1
000141
Mean
2.0 1.8
Subtotal
R ating: M oderately i r r it a t in g
Primary I r r it a t io n Index: 3.2/8.
Key: Er. = Erythema Ed. = Edema
1.7 6.3
0.8
- Albino Rabbits
Irrita tio n Scores fo r In tact
Skin S it e s a f t e r Removal:
1 Hour
48 Hours
E r. Ed. Er. Ed.
22
2
1
22 1 1
22 2 0
22 2 1
22 2 1
22 2 1
2.0 1.8 6.6
0.8
to o
TEST:
Acute Primary Skin Irritation Test
Ap p e n d ix I Riker Experiment No.: 0883EB0288
PROTOCOL
5.
S P O N S O R : 3 M ____C om m ercial C h e m ic a l_______________________________________________________ __ D ivision
C O N D U C TE D BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota
TE S T ARTICLE:
T- 3421__________________________________________________________________________________
CO N TR OL ARTICLE:
_____________________________________________________________________ _________
t
PROPOSED STARTING/COMPLETION DATE OF TE S T: . U '
~ ^ ' 5-'~>______________________ _
T E S T S Y S T E M : Female New Zealand White Albino Rabbits
SOURCE:
r-, --
r
BESTCOPY AVAILABLE
O B J E C T IV E : To determine the irritation potential of the test article to the skin of 6 animals. Rabbits were selected as the test system due to their historical use, sensitivity to irritants, ease of handling and general availability.
METHOD:
The animals will be housed in standard wire-mesh cages in temperature and humidity controlled rooms
with food and water offered ad libitum. Each animal will be assigned a numbered ear tag, which will
correspond to a card affixed to the outside of the cage. Prior to the application of the test article, the hair
will be clipped from the back and flanks of each animal a n d ______ _2______ test sites selected lateral
to the midline of the back approximately ten centimeters apart, i of the2_____sites will be abraded
by making four epidermal incisions, two perpendicular to the other two, while the other test site(s) will
remain intact. The test article (__ 0 .5 .grams----------) will be applied to i
abraded a n d ___ 1
intact site(s) on each animal, covered with -- gujaze_________and secured with
The trunk of each animal will then be wrapped with impervious plastic sheeting which will occlude the
test article during the 1 day exposure period. One hour and 48 hours after removal of the test article,
the intact and abraded test sites will be examined and scored separately for erythema and edema on a
graded scale of 0 to 4b. The average irritation produced will be evaluated by adding the mean scores
for erythema and edema of the intact test sites one and 48 hours post removal of the test article. Simi
larly, the mean scores for erythema and edema of the abraded test sites will be added. These two
values will be totaled and divided by four to obtain the mean primary irritation index and then assigned
a descriptive primary skin irritation rating as follows:
Mean Primary Irritation Score
0 0.1 - 0. 5 0.6-1.5 1.6 -3. 0 3.1-50 5.1 - 6.5 6.6 - 8.0
Descriptive Rating
Non-irritating Minimally Irritating j Slightly Irritating ' Mildly Irritating : Moderately Irritating Severely Irritating Extremely Irritating '*
' . "! 1 f< I TPq
1
3
? j
j
The rating for a test article may be increased if the reaction caused is beyond erythema and edema and are deemed to be of importance in the interpretation of the results. All raw data generated by the study director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota.
Purina Rabbit Chow, Ralston Purina Co., St. Louis, Missouri b Draize: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics (1965) s V r) D P ub^Ted by the Editorial Committee of the Association of Food and Drug Officials of the United States.
Sponsor
9-83 Date
/ 4. ^ 'w
Study Director
000142
, ,__}_>*<r *JT.
Date
APPENDIX I I P rin c ip a l p a rtic ip a tin g Personnel Involved in the Study
Name D. M. M arkoe, J r . , BS K. L . E b b en s, BS K. D. O 'M a lle y , BS G. C . p ecore
F u n ctio n
T oxicologist Study D irector
S u p e rv iso r Toxicology T estin g
Senior T o x ico lo g ist Acute T oxicology
S u p e rv iso r Animal L ab o rato ry
6.
000143
APPENDIX I I I
7.
T est and/or C ontrol A rtic le C h aracterizatio n
fo
k i /} fcCX3C/-C/)
T -242-1
1 . The i d e n t i t y s t r e n g t h , u n i f o r m i t y , c o m p o s it io n , p u r i t y o r o t h e r p e r
tin en t c h a ra c te riz a tio n s o f the t e s t and/or co n tro l su b stan ces have
been determ ined and documented a s o f
&,s Z %
2 . The method o f s y n t h e s is or o r i g i n o f th e t e s t and c o n tr o l s u b s ta n c e s ,
in clu d in g th e ir amount and th e method o f b io a ssa y ( i f a p p lic a b le ) i s
docum ented.
.S
y e s l' no
3. The s t a b i l i t y o f th e t e s t a n d /o r c o n tr o l su b sta n c e s have been d e t e r
mined o r w i l l be d eterm ined a s o f
u . 1 f 3 i <.t
The above in fo rm atio n and docum entation a r e lo c a te d in th e s p o n s o r 's r e cords.
Q Lj L
Sponsor
5 U s S3
D ate
L o C- A c
UJ. ri.
k P J/
IO
n
22-3 - (e5 ^
JiO -/
000144
-- c-,\/ed
JU N 1 3 1933
.'V7'L i i
BEST COPY AVAILABLE
APPENDIX IV
QUALITY ASSURANCE STATEMENT
Acute T oxicology Laboratory S tu d ie s
Study N o.:
C '> 3 c j ? .>
T h is s h o r t term stu d y was a u d ite d by C om pliance A u d it and th e
f i n a l re p o rt examined a g a in s t the raw d a ta on
/Y /1 ?
The r e s u l t s of the a u d it were re p o rte d to the stu d y d ir e c t o r and to
management on _____ ^ _^ ^ 9 /y In a d d itio n to the d a ta a u d it, d if f e r e n t s i g n i f i c a n t p h a se s fo r
stu d ie s underway in the Acute T oxicology L ab o rato ry are in sp e c te d
weekly on a re c u rr in g c y c le , and the f a c i l i t i e s a r e exam ined by
C om plian ce A u d it on a th r e e month s c h e d u le .
Compliance Audit Date
r
000145
