Document DdY63JvkL77qwv603zQrqg19M
HAZLR;'CON LABC)RATC)Rlr=S ARAF-RICA. INC.
3301 KINSMAN BLVD. P.O.BOX 7545 MADISON, WISCONSIN 53707
Chem'lca&lBloMedicaSlciencesDivision
PHONE (608)241-4471 TLX 703956 HAZRAL MDS UD
REPORT OF ANALYSIS
W. C. MCCORMICK MINNESOTA MINING AND
TOXICOLOGY SERVICES ST. PAUL, MN 55101
MANUFACTURING
SAMPLE: T-3610 PURCHASE ORDER NUMBERT T351371
SAMPLE NUMBER: DATE ENTERED:
REPORT PRINTED:
40703 07/19 10/0@
ENCLOSED:
GUINEA PIG MAXIMIZATION RAW DATA APPENDIX
METHOD, SUMMARY
SIGNED:
STEVEN M. GLAZA STUDY DIRECTOR ACUTE TOXICOLOGY
BY AND FOR HAZLETON LABORATORIES AMERICA., INC.
RAW DATA-FOR THIS STUDY ARE KEPT ON FILE AT HAZLETON AMERICA, INC., MADISON, WISCONSIN.
LABORATORIES
WHAZLOTON
LABORA TOR(ES AFVIE:PICA.
Chemical& BloMedicaSlciencesDivision
3301KINSMAN BLVD.o P.O.BOX 7545* MADISON,WISCONSIN 53707 PHONE (6082)41-447*1TLX 703956HAZRAL MDS UD
SAMPLE NUMBER: 40703985
SAMPLE:
T-3610
PAGE
2
GUINEA PIG MAXIMIZATION
Test Animal: Young adult male albino guinea pigs of the Hartley strain were
orocured, maintained individually in stainles5-5teel cages in temperature-
@nd humiditj-controlled
rooms, provided continuous access to Purina Guinea
Pig Chow an@ water and held for an acclimation, period of at least 7 da!.,@s.
The animals were identified by animal number and corresponding ear tag.
Test System: Fourteen male albino guinea pigs, weighing between 430 g and
568 g, were chosen at random for this study. The animals were divided
into two groups consisting of a test group of 10 animals control group of four animals. A common vehicle control
and a naive group of ten
animals,'weighing
between 473 g and 553 g, was utilized for this studj
and Study N05. 40703984 and 40705145.
D05e
Range Study:
The purpose of the range-finding
study was to find a
moderately irritatina dose level to use for the topical application
and a 5ubirritating @oncentration to be' used for the challenge applicatil
Four additional animals were treated with the test material at concen-
tration5 of 25, 50, 75 and 90,% w/v in 80% ethanol/di5tilled
water.
The test mixtures were applied to 2.0 x 2.0-cm Whatman No. 3 filter pape
which were applied to the shaved animals' baCk5 and were then overwrappe
with Blenderm and Elastoplast tapes. The dreS5ings remained in place fc
24 hours.
The test
5iteS
were evaluated for dermal irritation 24 and
48 hours after bandage removal. Based upon the results obtained, the
test material was administered a5 a 90% w/v suspension for the topical
and challenge applications.
Preparation of Test Material:
Intradermal Injection5
Solution No. was prepared in increments
1: The Freund'5 Complete Adjuvant Solution by adding 3.0 mi of sterile water for injection
to 3.0 ml of Fraund'5 Complete Adjuvant.
Solution No. 2: A 5% w/v mixture was prepared by weighing
0.50 g of T-3610 into a 30-ml beaker and adding 80% ethanol/
distilled
wate'r to a total volume of 10.0 ml.
Solution No. 3: A 5% w/v mixture of test material in Freund'5 Adjuvant was prepared by adding 2.0 ml of a 10% w/v suspension of T-3610 in 80% ethanol/distilled water in
increments to 2.0 ml of Freund'5 Complete Adjuvant.
For the topical induction and challenge application, the test materia was administered as a 90!4w/v sue-pension in 80,%ethanol/distilled wat
EHAZLCTON
LABORATORIES
AMERICA,
INC
3301 KFNSMAN BLVD, o P.O.BOX 7545 MADISON, WISCONSIN 53707
Chemical& BioMedicalSciencesDivision
PHONE (608)241-4471 TLX 703956HAZRAL MDS UD
SI:@MPLE NUMBER: 4'0'/-;'039e5 SAR(PLE: T-3610
PACE
GUINEA PIG MAXIMIZATION
(CONTINUED)
Prp-loaration of @iehicle Control Mixtures:
Intradermal Injections
Solution No. was lorepared in increments
1: The Freund'5 Complete Adiu,.,ant Solution bj addinq 3.0 ml of sterile water for injection
to 3.0 ml of Freund'5 Complete Adjuvant.
Solution No. 2: A 5% w/t-)mixture of 80,1,ethanol/distilled water in sterile water was prepared b,,,a,dding 0.5 g of P,05i ethanol,,'dl:Btllled water into a 30 ml beaker and adding sterile water for injection to a total volume of 10 ml.
Solution No. 3: A 5,1 w./v mixture of 80% et@ianol/distilled
water in Freund's Adiuvant was pr epared by adding 1.3 ml of
a 10% wl,.)mixture of 80% ethanol,/di5tilled
water in sterile
water for injection in increments to 1.3 ml of Freund's
Adjuvant.
For the control
topical animals
induction and challenge
application , the vehicle
were treated with eO% ethanol
in distilled
water.
All and
L,,ehicle control do5ina.
mixture5
were thorouc3hl@,, stirred
during preparatiot
Method:
A 4.0 x 6.0-cm area was clipped along the midline over the shou
rea-ion. Two rolqs of three-deep
intradermal
in iections (total of 51X
in.iection 5iteS) were made within the boundaries ' of a 2.0 x 4.0-cm are
one row on each side of the midline as fOllOW5 per site:
0.05 ml of t
prepared
Freund's
Ad iuvant Solution,
0.05 ml of the 5% w/'v test mtixtur
and 0.05 rtilof the 15'% wll,.;test material
in Freund's Complete Adjuvant
mixture.
The respective vehicle control mixtures were administered
to the vehicle control animals in a similar manner.
Because the test and vehicle control materials were non-irritatina, t areas of the intradermal in3-eCtiCn5 were pretreated with a 10,% w/Lo sodium lauryl sulfate (SLS) suspension in petrolatum 24 hours prior t topical application. Six da@..,a5fter the intrader-mal injections the I area was closely shaved and the 10,% SLS was massaged into the skin Lj: a ala55 rod. TLqent@,,-fourhours after pretreatment a 2.0 x 4.0-cm pa' o@ (,JhatmanNo. 3 filter paper Wa5 saturated with a 90% L-J/V 5us oerisio, of T-3610 in 8051 ethanol/distilled water, placed ok,,erthe inje'ction then covered with an overlapping of E31enderm tape and secured b,,jan c@.,erLoraDof Elastoplast tape. The dr,es5ina, remained in place for '413hours. The vehicle control animals L.,ierdeosed in the same manneri.isiriSoO% ethanol/di5tilled water only.
HAZLrmuCON LABORATORIES ANOERICA, INC
Chemical& BloMedicaSlciencesDivision
3301KINSMAN BLVD.o P.O.BOX 7545- MADISON,WISCONSIN53707 PHONE (6082)41-447a1TLX 703956HAZRAL MDS UD
SAMPLE NUM13ER: 40703985
SAMPLE:
T-3610
PAGE
GUINEA PIG MAXIMIZATION
(CONTINUED)
Two weeks after topical induction the test and naive control (previously
untreated) animals received a challenge do5e. The hair was removed
from a 5.0 x 5.0-cm area on the right flank by shaving as before. The
90% w/v suspension of test material in 80% ethanol/di5tilled
water
Wa5 applied to saturation on a 2.0 x 2.0-cm piece of filter paper. The
vehicle control animals were dosed in the same manner U5ina
80,% ethanol/
distilled water. The patch Was 5ealed
to the right flank @or 24 hours
under strips of Blenderm tape. Complete occlusion was made by an overwr
with Ela5tOpla5t
tape wound around the trunk.
Observations:
Twent_y-four hours following patch removal the test sites Lqe
examined for erythema and edema. The 5itOS were examined again at 48 hc
after patch removal to detect any week, slowly developina reactions.
Ti-
test sites were 5ha-ved 3 hours prior to the 24-hour reading. The react
were 5Cored according to the following.4-point
scale:
0 = no reaction 1 - scattered mild redness 2 = moderate and diffuse redness 3 = intense redness and swelling
The important
5en5itiZatiOn.
statistic in maximization not the intensity.
testing is the frequency of
Pathology: disca;ded.
At study
termination all animals Maximization Ratings
were
euthanatized
and
Sensitization Rate
0% ill loz 40% 70% -
9% 39% 69Yo 100%
Classification
Not a Skin Sensitizer Weak Sensitizer Mild Sensitizer Moderate Sensitizer Strong Sensitizer
HAZLOTON
LABC)PTATORIES ANIERICA. INC.
Chemical& BloMedicaSlciencesDivision
3301KINSMAN BLVD.o P.O.BOX 7545 MADISON,WISCONSIN 53707 PHONE (6082)41-4471TLX 703958HAZRAL MDS UD
SAMPLE NUMBER: 4070398@;
SAMPLE:
T-3610
GUINEA PIG MAXIMIZATION
(CONTINUED)
Test Animal: Albino guinea pigs
Source: Hazleton Dutchland, Inc., Denver
Date Animals Received:
07110 and 07/24/e4
Date Test Started: 08/08/84
Date
PA Test
Completed:
Test Material: T-3610
Dermal Reactions to Challenge Application
PRGE 09107164
Animal Number
24-Hour Score
48-Hour Score
Test Gr.oup
EO-2132
0
0
EO-2134
0
0
EO-2136
0
0
EO-2137
a
0
EO-2138
0
0
EO-2139
0
a
EO-2141
a
0
EO-2142
0
0
EO-2143
0
0
EO-2144
1
1
Average Score
0.1
0.1
EO-2150 EO-2147
EO-2148
EO-2145
Average Score
Naive Control Group
0
0
0
.0
0
0
0
0
0.0
0.0
HAZLOTON
LABORATC)PTES AN@C-PICA. lr%C.
Chemical& SloMedicaSlciencesDivision
3301KINSMAN BLVD.a P.O.BOX 7545o MADISON,WISCONSIN 53707 PHONE (6082)41-447-1TLX703956HAZRAL MDS UD
SAMPLE IIUMBER*. 40703985
SAMPLE:
T-3610
PAGE
6
GUINEA
PIG MAXIMIZATION Vehicle Control
(80% Ethanol
(CONTINUED) in Distilled
Water)
Animal
Number
24-Hour Scare
48-Hour Score
Test Group
EO-2030
0
0
EO-2027
0
0
EO-2051
0
0
EO-2052
0
0
EO-2053
0
0
EO-2135
0
0
EO-2140
1
0
EO-2054
0
0
EO-2055
0
0
EO-2056
0
0
Average Score
0.1
0.0
General Behavior and Appearance: All of the guinea pigs used in this stud appeared normal throughout the study period with the exception of one vehicle control group animal, EO-2140, which had diarrhea on Day 3.
Normal body weight gains were recorded for all animals during the study with the exception of one vehicle control group animal which exhibited a body weight loss of 3 g during the first week of the study and one test animal which exhibited a body weight loss of 67 g during the secon, week. During the last three days of the study, nine test, three naive control and five vehicle control animals exhibited body weight losses of 2-28 g.
Skin Reactions to T-3610: A slight dermal reacti-on wa5 observed in one test aroup animal at 24 and 48 hours following the challenge application. The dermal reaction in this animal (No. EO-2144) was possibly cau5ed by tape irritation. The other nine test group and all of the naive control animals did not react to the challenge application of the test material. A slicht dermal reaction was observed in one vehic control animal following the challenge application with 80% ethanol/ distilled water.
Conclusion: Based on the results obtained, the test material, T-3610, is not considered to be a skin sen5itizer in guinea pigs.
HAZLETON
LABCY:qATORtrzS AftAERICA, INC,
Chemical& SloMedicaSlciencesDivision
3301KINSMAN BLVD.o P.O.BOX 7545* MADISON,WISCONSIN 53707o PHONE (6082)41-44791TLX 703956HAZRAL MOS UD
SAMPLE NUMBER: 40703965
SAMPLE:
T-3610
PAGE
7
GUINEA PIG MAXIMIZATION
(CONTINUED)
References:
1. Magnusson, B., MD, and A. Kligmanj PhD, MD, Allergic Contact Dermatitis in the Guinea Pig, Charles C. Thomas Pub., PP. 113-117 (1970).
2. Hitch, R.K., "Dermal Sensitization Studv," Pesticide Assessment
Guidelines, Subdivision F, Hazard Evalu@tion:
Human and Domestic
Animal5, U.S. Environmental Protection Agency Office of Pesticide
and Toxic Substance Series 61-1, pp. 59-62, November 1982.
Test Group: Positive Control Group Veh:Lcle Control Group Naive Control Group
Guinea Pigs Daily Observations
RT No. Roca No.
T- 3&10
Vah:Lcle___
...
Veblele pj)4
Animl ffm r
Teeb-
Date
A)- -A,3
Ad
Al IV --iV
A/ ti A) 0
A)
-A/ 'A/
AJ -Al
/J k)
A)
A)
AJ A)
A/
A/ -M
N Ai Ni AJ
Al A/ 4/ Al
AJ A) --A) A)
ri ti @j I @j
SP 1 -16
7 2&1
oc,//q t
A6J
AJ
I\J AJ
m
INV N
fl.2
A) A) A) A)
A)
--Al Al A/- A) A/
__m
AJ
A) @J @J AJ Al
A) -A) A)
A]
@i N Al
A) --@J t\J I I\i s
e-,@,12 ?-.2r
e-30
BOTZTT=Mouqy *TqTsTA oN N
v /v /v IV 7V- -7r IV tv IV N
C)5
tv (V
d
(V
. ..1.!..;;fiy IV- I
IV /V /V tv [V /V
(Y. (Y /I (Y @y
bi (-NJ
OTOTROA
0--7 Ssq=V TOWM CY
Glldvv"FZ-
STOTROA OTOTROA
0 1O)E'--L
-S@862OZO17
*ON MOOR *ON 11
GMOTZ*Ajaeqo ATT*A - aSTsi V=Ttva
duol!) TO-12ucO DATVK duazo To,%2u*D *T*TQOA dn oze Toz2uoo *A';ZTooa
:dnoze 2s-o3;
G=QFA PIG XhrnaZATICN TEST
Test Compound Date An4-Is Received Date of Intradermal Tzjactions Bat* of Topi@ia Application Data of Challeng*
T(r" 6 ro"lp RT No - "/070 3 r?l
Source @kzlelvn6
Tacbmician Tactaiciau Tachnici=
24 Rours
A"4,mml No., S*X 017
Right
L&ft
VI,3)
0
013(l ------- 0
13
9137
1213R
0
3'@
0
.0
--- 2)q3
0
48 Ecurs Riaht
Left
0
Tacbzician
Recorded-By
6p
Data
@p 9/-7
Scarius Code:
0 - ,formal,.30Reaction a Scattered Ylld Redness - Moderate and Dif.*use Redness
3 a tacwso Redness and Swelling
"-'Test Group-. Positive Control Group
Vehicle ControlGroup
Naive Control Group
Guinea Pigs Body Weights (gramg)
RT No. 9/070,32E6
3&10
Vehicle Wo
Vehicle
Mq
N-A
Vehicle A)fi
Animal Number
Techrilcian Date
tAlir3 5-,3q 400
Of-
S"?7 (ol-7
(081
-7(o
5-37 5S-@57
6 o g-
SYY
.430
li"'1(4 S;P 4(
5-79
IL3,4 &to
qS7
din Sol
51,6
&32 653
4ys
4 ig.
'5-/,3
M IA.2- 1-4
I"7a 9--.2
S@,qe)
S-gq .:;@x yp ?L@ 7
Animal Number
%%Lkz ZIL4b 21 %4LA
Technlcian
bil
'Y91
509'
5-/7
57SZ3
573
6-714
-F
'iA- Not Applicable
g(o 2(@:,
Scale Used: Scale Used:
%,,Tgcit4i3i4R
ron 1501,9
5fD-
Scale Us ed: k-rrokl
Scale Used: krtaa
ScaleUsed: K-rrc"t"l
Scale Used:
Reviewed by
Date
MA it, SP
Guinea Pigs Body Weights (grams)
Test Group: Positive Control Group Vehicle Control Group Naive Control Group
NA
@jA-
36/0
Vehicle Vehicle
Vehicle
Animal Number Co-
I-LA
141
56%
5o7
i.o
RT bro.1-107039?
A)t4
Technician
Date
19:?y
tAA
-7YA-
P/7
L NA Not Applicable
Animal- Number &70
Tech-
nician
D
Scale Used:
Scale Used:
i<
Scale Used:---97-MAI
Scale Used: t-I
Scale Used:--k
scal e- Ts-e-cT
Reviewed by
i-3LIt
1-1
/15,0/g
is-a)9
7
Ai6. sp
o
ate 9-1 0
9,>@ OilZ4 124
T*st Group: Positive Control Group Vehicle Control Group Naive Control Group
RT No. Y0703995Room No.
Guinea Pigs Daily Observations
A)A
. Vehicle
@JA
Vehicle
----T-3&10
Vehicle
Animal Number 60 -
Tech-
Date
199
A)
A)
A)
AJ A)
w
Al
A/
AJ A/
,@J A) /NJ
K) M
Aj
A)
Al I
Aj 'Ai
l@j
A/ A/ A)
A). AJ
iQ
N - &No Visible Abnormalities MA - Not Lpplicable
sp g.
Le 8
*TqvzTTddY 2on - vj,, RDTZTTWWCMQV *TqTsIA ON - x
6 .,b 41@*
(V fV -fV'
7V@ t-v tv 79
IV fv IV
-b -YrA
/'Y ify Iry /Y
Th7c
*TzTqOA
o_:ploc
DTOTROA OTZTQ&A
-V(V (Y
-ON wool
ON z-1
BuOT39AJOsqO ITTva - SsTa woutrto
dvk*-ZS TCL%3ucyJ OATVN dimoso -razzuoo 9TOT4*A dnojo yozzuoo *AT2T9oi
:dnozo 2901
4a t4 C31
vl
ast Group.*
Posit:CiovnotrGorlasp
Vehicle Control Group Naive Control Group
camm Pigs Body Weights (grams)
Ar
Vehicle
qO70iiVr RT No. q,0.71)-39?5(
eIC701995
tiA
ILIC&L@f- vehicle
Aulaal Number Eo-
Z05i-
2-05:N 2.1,Ns Limo
Tech-
nician
Date
14-111 4irl
m* ILA
S,9y.
(0(;L
to
-ff*7 M7
?.'7
Ani=a
bar
ZOSS Z056
ft,3 520
mo
!5'74
59(a S3&(3(.:
416 0.
AgIng
Scale Used:
S:OUas*ed: vtrom
Seal* U"d: kTrniA
ScalUesed:
ScaleUsed:
Scale Used:
T.f-A Not Applicable
Reviewed by
Tftbnician
192
*n
Date
Gain*& Pi#s Daily Obs*rvations
IT NO. Rom No.
Test group:
MA
Vehicle
A.)
Positive Control G"up
Vehicle
A)h
Vehicoloemgirou9p07Loc&noI!ss-'@,H'iled
Xelve concrel group
Vehicle
--n27
Animal Nmbow eo
xg;@ a?os--l@13r 07/go L -105q
T*Ch-
ste@um
D& to
ffy
A/ i AJ
IIJ
AJ
Al
tJ
AJ AJ
AJ
AJ
@j
A)
4.* Al
0
NI
A]
tj
Al Al
A/ Aj
A-1
e-,&T6-//,
/V /V /V 4/' /@j /V .AOI':Aol ea rill
Al
A41 Al
Al
A.1 @ER
@rl.-Q
A) A) -AJ Aj Ai AJ Al A[ A) AJ 1120F
I\i 'Ai @j
A) &)
m
Diarr+" ;se 1-14-ly
If - No V:LslUa Abmr=Llitles
NA - *cc ApWc&W&
AJ AJ A) AS
/70
Al AJ
L
@j 0 q
SP
Test Group: -fteltiveControlGroup Vehicle Coacrol group
Naive ControlGroup
Qdnaa Pigs Daily Observations
IT No @v 7 Roos NO:
PiA
&A-9-40-"
OA-
n.@c r
Vehicle
vehicle
Vehicle
AAIN@al Ymber
Pal xsl dogg--,-VS3 ;@/4(0 A6@
Tecb-
Dat
sician
Al A)
AJ Al
/j
dZ6
A]
A/
AJ
Af
A) AJ A]
@J A] A)
4St4A- 9. sp
A/ A/ -Al A/
Al
A/-
A/
A.1
N - Be VisibleAbwraalities MA - Not kppllc&bu
=nqzk nr, mATym"Avw
Test Compomd
pa Result
Date Aulmls Received Date of Intraduu&l zujw*vioua
Date of Topii&L ApplicAtim Dataof ;b&Llaw
Wa-tcr
/q
gq 4;12 @f-
-"-a
9-q- ecl
Uc@@cle-
GroLtp
qo7o5-lq5'
IT 50.
41070319,?Y
C/o70 3-2z 67.:
Sponwr No.
t@iA
so=cs/i6z/e4o[p)ia
Tachnef-a,n'
Tecl,4cfa,
'MCA
Tac%n4c4@n
Auln&L So-I Sft
070
o?a27
X=
24 saw"
R:L]Lft
0
0 0
Left
0
0 1
48 Imrs Usht
Left
R4kcarded
By
Data
AP
sp
5
sp
searing code:
0 - ammml, go R"ctton L a Scattered UlU Badness
2 - N*4*rata and Diffu" ladness 3 - TAC@mn Redness and Swelling
LI)
e rro-e- 1-;a
3T:
'sp
UTMO
DA=:
bose-RcLh ck
Guinea Pigs - Body Weights (grams)
RT No.
,--TestGroup:
T
Positive Control Group
NA
Vehicle Control Group
N
Naive Control Group
Vehicle Vehicle
E7qaoolloj@@A
Vehicle
Animal Number Eo
0 -via lq3@;- -.LIOS'
to
Technician
Dat(
5-39 5 to0
5p
NA Not Applicable
Animal Number
Tech-
aician
D
Scale Used: I<TrC)n
:@@@ale
Used:
Scal'eUse@
Scale Used:
Scale Used:
Scale Used:
Reviewed by
15c>lq
Date
SP 3-(
0 s e, -i@OlLnl (@e,
Guinea Pigs Daily Observations
RT No. Room No.
Test Group: Positive Control Group Vehicle Control Group Naive Control Group
3 (c10 NA A
Animal Number
loaz,
ZLOIS aot 6
N
Al @j fv
N
/@j f@j
Vehicle go?o 6-lAa,7ollf);s4)'iled
Vehicle
A.
Vehicle
)\AI
Technician
SP
Date
19
3--s
.. ................
Dose. PAohoje,
conmi nrv
ON T=
Test Camomd Data AnUaLs Rwoiv". Date of Data of TaVLaa AWLL"tim Data of Challow
1C) WA ISq-
IT No sawes
40 o-3q35'
"amle--@onDu+cklani
NA
Twbu@
-ki
Aulml to .. 94M 60 - 2.0 a:z..
sa_
24 4/,lunhe
0 .6
L-4ft A64, 0
-0
48 Bmrs
Left
,-ao. Iin
so%
9070 0
Tacbniclm Ueovded BY
Dar.&
90 91//0
scwftg co":
a mm=Lt so Uwttm L S"rroz@" Itiu Uft"s
7.a Hodo=Ca Md 1):Uftnlewft"s 3 a lutwas left"s a" Sw4LLI=g
IRee-CY4!A@Error 9.%-R4 st
<IMM
