Document 6Rq1dnGjnLd6Nxp1BMDXNzZZg
-4
HAZLOTON
L"BDPffDRIES
ANFERICA
INC
Chemica&l BioMedicaSlcienceDsivision
@'N@iol orK.I-NSsMoAN BLVD. - P.O.BOX 7545 * MADISON, WISCONSIN 63707 PHONE (6082)41-4471* TLX 703956HAZRAL MDS UD
FINAL REPORT
ROGER PERKINS
MINNESOTA
MINING &
TOXICOLOGY ST. PAUL,
SERVICES MN 55101
MANUFACTURING
COMPANY
PURCHASE ORDER NUMBER: T837389-410 712
SAMPLE NUMBER: 70100355
SAMPLE ENTERED:
REPORT PRINTED:
01/07/'8-/-@
01,1,.)/-/
ENCLOSED:
PRIMARY EYE IRRITATION STUDY IN RABBITS
RAW DATA APPENDIX
METHOD,, summAR@,
SIGNED:
I.....................
STEVEN M. GLAZA
STUC,@' DIRECTOR ACUTE TOXICOLOG@'
........
DATE
.........
BY AND FOR HAZLETON
LABORATORIES
AMERICA,
INC.
RAW DATA AMERICA,
FOR THIS STUDY INC., MADISON,
ARE KEPT ON FILE WISCONSIN.
AT HAZLETON
LABORATORIES
r@@.-'HAZLETONLMBDR=URir=S AKAERICA, INC
Chemical& BloMedicalSciencesDivision
MADISON, WISCONSIN 53707 - PHONE (6082)41-4471o TLX 703966HAZRAL MDS UD 3301 KINSMAN BLVD. - P.O.BOX 7645
SAMPLE NUMBER: 70100355
SAMPLE:
T-4016
PAGE
EYE IRRITATION
Objective:
To determine the level of irritation
single exposure of a test material to one eye
according to the U.S. Environmental
Protection
Testino Pesticides
and Toxic Substances.
produced of albino
Agencyl5
following rabbits Guidelines
a
for
Test Material:
T-4016
Physical De5cription:
Purity and Stability:
Thick brown liquid Spon5or a55ume5 responsibility stability determinations.
for purity and
Test Animal:
Young adult rabbits of the New Zealand
procured, maintained
individually
in 5creen-bottom
and humidity-controlled
quarters, provided access
and a measured amount of Purina High Fiber Rabbit
an acclimation
period of at least
7 days.
White strain were cages in temperatureto water ad libitum Chow, and held for
Six acclimated
animals, weighing from 2354 to 2514 g, were ch05en at
random for the test.
The animal5' eyes were examined within 24 hours
prior to test material administration
Using sodium fluorescein dye
procedures.
Onlv those animals with no sign of ocular injury or
irritation were used on the test.
Test animals were identified by
animal number and corresponding
ear tag.
Reason for Species animal of choice
Selection: based upon
The New Zealand White albino rabbit 15 the
its large orbit and nonplqmented
-'Iris.
Preparation
of Test Material;
was not determined.
The sample was dosed as received.
The pH
Treatment:
Each rabbit received 0.1 ml of the liquid test material placed
on the everted lower lid of one eyey with the contralateral
eye serving
as the untreated control.
The upper and lower lids were gently held
together for one second to prevent 1055 Of material and then released.
The eyes of the rabbits remained unflU5hed.
Reason for based on
Route of Administration: the method of Draize.
Historically,
the route of choice
HAZLETON
3301 KINSMAN BLVD. - P.O. BOX 7545 - MADISON,
WISCONSIN
Chemical& BioMedicalSciencesDivision
53707 9 PHONE (608) 241-4471 o TLX 703956 HAZRAL MDS UD
PAGE SAMPLE NUM13ER: 70100355
SAMPLE: T-4016
EYE IRRITATION
(CONTINUED)
Ob5ervation5:
The treated eyes were ob5erved for ocular irritation at
11 24, 48, 72 and 96 hours after treatment.
At the 72-hour reading,
POS5ible
corneal
injury.
the Draize technique.
sodium fluorescein Was
Irritation
Was qraded
used and
to aid scored
in revealing
accordinq
to
Animals were weighed iU5t prior to test material administration.
Pathology: discarded.
At study
termination
all animals were euthanatized
and
HAZLOOCON LMX3=.XrC)RIES APVERICA. lrlf-
Chemical& BioMedicalSciencesDivision
,*i--
-
3301KINSMAN BLVD. - P.O.BOX 7545 - MADISON, WISCONSIN 53707- PHONE (6082)41."71 - TLX 703956HAZRAL MOS UD
QAMPLE NUMBER: 70100355
SAMPLE:
7-4016
PAGE
4
EYE IRRITATION
SUMMARY
(CONTINUED)
Test Animal:
Albino rabbits - New Zealand White
Source:
Hazleton Research Products, Inc., Denver PA
Date Animals Received:
12/16/86
Date Test Started:
01/08/67
Date Test Compieted:
Oi,-12,,87
PRIMAR@' EYE IRRITATION
OBSERUATION
PERIOD
1 Ho u r : 24 Hours: 48 Hours: 72 Hours: 96 Hours:
SCORES*
6 Rabbit Mean 0.1 ml
(Unwashed)
22.7 25.7 12.5
5.7 0.0
The Primary for all the observation
Eye Irritation Score is the total eye irritation animals divided by the number of animals (6) at period.
score each
"-4AZLE'tCNL-M)R@IES
"IC
3301 KINSMAN BLVD. - P.O. BOX 7545 - MADISON, WISCONSIN
Chemical& B!oMedicalSciencesDivision
53707 o PHONE (608)241-4471 o TLX 703956 HAZRAL MDS UD
SAMPLE NUMBER: 701003155 SAMPLE: T-4016
EYE IRRITATION
Animal Number FI'0208
F16219
F16220
F16221
F16222
F16223
Observation Period
I Hour 24 Hours 48 Hours 72 Hours 96 Hours
1 Hour 24 Hours 48 Hours 72 Hours 96 Hours
1 Hour 24 Hours 48 Hours 72 Hours 96 Hours
I Hour 24 Hours 48 Hours "-@2 Hours 96 Hours
I Hour 24 Hours 48 Hours 72 Hours 96 Hours
I Hour 24 Hours 48 Hours 72 Hours
96 Hours
PAGE
5
(CONTINUED)
Table I Individual Eye Irritation Scares
Cornea
A
B
0
0
1
3
1
1
0
0
0
0
Score AXE3x5
0 15
5 0 0
Iris Score
A
A x 15
1
5
1
13
0
0
0
0
0
0
Conjunctivae
A
B
c
3
4
3
2
3
2
2
0
2
1
0
0
0
0
0
0
0
1
5
3
4
1
20
1
5
3
4
3
1
1
5
1
5
3
3
1
0
0
0
0
0
2
2
1
0
0
0
0
0
0
0
0
0
0
0
1
5
3
3
1
1
15
1
5
3
0
0
0
1
5
2
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
5
3
4
1
1
5
1
F,
3
4
1
0
0
0
1
5
2
1
1
0
0
0
0
0
2
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
5
3
14
0
0
3
2
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
i
3
-:>
0
0
0
1
0
0
0
0
0
2
0
1
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
Score (A+B+C)'@,
211 14
6 0
18 20 14 10
0
16 12
e 6 0
18 16
e
6 0
le 14
8 4 0
16 8 4 2
0
HAZLETON L-M)-@IES
AfV*F;ICA. ltJC
Chemical& B!oMedicalSciencesDivision
TLX 703956HAZRAL MDS UD 3301 KINSMAN BLVD. - P.O.BOX 7545 - MADISON, WISCONSIN 53707o PHONE (6082)41-4471
SAMPLE NUMBER: 70100355
SAMPLE:
T-4016
EYE IRRITATION
(CONTINUED)
Sodium
Table -?
Fluorescein
Examination
Animal Number
Fib2O8 F16219 F16220 F16221 F16222 F16223
Observation Pre-initiation
NEG NEG NEG NEG NEG NEG
Period 7el Hours
114r,- L@
NEG NEG NEG NEG NEG
NEG = No stain retention POS = Positive 5tain retention (area of cornea involved).
PAGE
6
Comments:
No pain response (vocalization) W85 instillation of the test material.
elicited from any animal follot@iinq
Blanching of the conjunctivae was seen in all six animals at 1 and 24 hours, in three animals at 48 hours anc in two animals at /7,1h1o-urz,.
Corneal epithelial peelinq was exhibited by four animals at 24 hours and by two animals at 48 hours.
References:
1. Hitr-Fi,R*.K..,"Primary Eye Irri*atior, Study," Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic
AniM8151,
U.S. Environmental Protection Hqency Office of Pesticide
and Toxic Substances
Series 81-4, pp. 51-55 (November 1982).
Draize, J.H. , "Apprai5al of the Safety of Chemicals in Food5, DrUq5,
and Cosmetics - Dermal Toxicitv." A550Ciation
of Food and Drug
Officials of the U.S., pp. 46-@9 (19/-5).
3. 21 CFR 58.
4. DHHS Publication No. (NIH 85-23 19e'.',)Guide for the Care and U5e of Laboratory Animals.
01
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Easily dincerniblg trunSIUCOnt-&rOsb,.detail*Of iri&
2*
Ali rLtIrODSOLU
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3*
barely discernible
Opaquw4.iris invis:LblAw
(31 ACISACMZM
'r-'ve*
one quarter (or lase), but not =rO Grmtar th@ am quarter,but IOM
halr
2
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ASS
(3) ZMIM"UM
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ToneeLsnorm"
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easily dlmoernible
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Difrom booty red
(B)Mona" nosweLLlag
Any vj*LUng
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7b* total war* for the @" Is the @ aormm, U-U. and eWmetAvedi@.
of &U sear@
to St&cred fixuree indicato.positive
4ffoct.
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Primary Eye Irritation Test Observations
est Material: Test Eye: Right
HLA No. Group:
Washed: PA@ seconds following instillation of test material,
the test eye was washed with
mL of lukewarm
tap water for NO, seconds.
L,@nwashed
Ariim&T No.
Location Of rnrneal Lesions
(9 ol C)
Tail ---- Head
Cornea - OpacitY
Area
Iris
Conjunctivae-
Redness
Chemosis Discharge Sodium Fluorescein Examl
tJA-
OBSERVATIOlt PERIOCI'a 19
houv-
Fr
I
A16
AIP
t>
N)4 ILIA
TechnicianDate
2tt!l
NA Not Applicable A Petite hemorrhage B alanching C Ciear disr-harge
0 - Purulent discharge E - Hair loss around the eye F - Necrotic Areas G - Unable to *.,4,sL:a7%'41,1ut-co-,-
severe swelling H - No reaction to light I - Injected
j KL1# 14 PR-
SPOS NEG -
Corneal epithelial damage,
Cornea.1 epithelial damage, Corneal epithelial damage, liypopyon Corneal neavascularizatioit
Pannus Unable to visualize due to ::cve-e opa=it.,, Granulation scar tissue Positi-ve-stainretention Negative stain retention
peeling piling pitting
C)eviewed By. (4253A)
Date.-
Eye I"itation Score:lz SFAA.-
Primary Eye Irritation Test Observations
est Material:
Test Eye: Right
LAC)tLO
HLA No. Group:
Washed: xj# seconds following instillation of test material,
the test eye was washed with
mL of lukewarm
tap water for L& seconds.
L.4n@w a s h e d
OBSERVATION PERIOD:
Animal No.
to
(0
Location of
Tc ail
Head
Cornea - Opacity
Are&
Iris ,@njCuonnjcutnctivae -
Redness
Chemosis Discharge
Sodium Fluorescein Exa-I
Technician-
Date I-@l-'97
rilvi I @l's
C,
t.P,,) N Pr Npr-.- N
C>
N4 I
NA - Not AppTicable
A - Petite hemorrhage B - Blanching C - Clear discharge
0 - Purulent discharge E - Hair loss around the eye F - Necrotic Areas
','.,abtleo vis,-.al".Zdc:;--c;
severe swelling H - No reaction to light
- Injected
jKLRItPR-
SPas NEG -
Corneal epithelial damage,
Corneal epithelial damage, Corneal epithelial damage, Hypo-pyofv Corneal neavascularization Paffnus Unable to visualize due to
savere opacity Granulation scar tissue Positi-ve-stainretention Negative stairt retention
peeling piling pitting
viewed By: (4253A)
Date:
-am%
Eye Irritation Score:
Primary Eye Irritation Test Observations
10 est material:
Test Eye: Right
HLA No. Group: ---K)pr
Washed: ALP, seconds following instillation of test material,
the test eye was washed with
mL of lukewarm
tap water for &I seconds.
L,-iTnwa sh ed
Animal No. Location or Corneal Lesions
OBSERVATION PERIOD'- qg hour.5
'FL--(901CI)OsR19 (aI;t0li (.all
Tail ---- Head
C)
Cornea - Opacity
Area
Iris
C>
,@riCjounnjcuntcit.ivvaaee -
Redness
Chemosis
Discharge
C)
Sodium Fluorescein Exam
m,4
N)q
Technician-
A) A-
A3
A)A
Date
0 C)
AJI'@
NA - Not Applicable
A - Petite hemorrhage R - glanching C - Clear discharge D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas G - Unable to -.IsL:alize-4L:cta
severe swetling
H - No reaction to light I - Injected
J Corneal epithelial damage, peeling
K Corneal epithelial damage, piling
L - Carceal epithelial damage, pitting
14 - Hypopyon
-
N - Corneal neovascularizatiorr
P - Pannus
R - Unable to visualize due to
severe op-"--@lity
S - Granulation scar tissue
POS - Positi-ve-stain retention
NEG - Negative stain retention
eviewed By.(4253A)
Date:
Eye Irritation Score: 7i4@
Primary Eye Irritation Test Observations
est Material: Test Eye: Riqht
HLA No. Group: Qpf
N,4 Washed: _&J_4seconds following instillation of test material,
the test eye was-washed with
mL of lukewarm
tap water for && seconds.
L@4n@washed
OBSERVATION PERIOD:
Animal No. Location of Corneal Lesions
Ft-
to a 19 -
(Ollaao
Tail Cornea
Head Opacity Area
n 10
Iris
Conjunctivae -
Redness
9L
Chemosis Discharge Sodium Fluorescein Examl
C-
N)ea
Technician 17>
Date
gLgLi I
;I
3 tpf,N@,
NA - Not Applicable A - Petite hemorrhage
B - Blanching C - Clear discharge D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas r. - Una-hieto visualize due to
severe swelling
H - No reactionto light I - Injected
J - Corneal epithelial damage, peeling
K - Corneal epithelial damage, piling
L - CorneaT epithelial damage, pitting 14 - Hypdpyon N - Corne&T neovascularizatiort
P - Pannus R - Unable to visualize due to
saverp opacity
S - Granulation scar tissue POS - Positive-stainretention NEG - Negative stain retention
iewed By-. o rv
(4253A)
Date:
Eye Irritation Score-4#moil-z%-%at
Primary Eye Irritation Test Observations
est material:
Test Eye: Riqht
HLA No. Group: opt
NPC Washed: ALA. seconds following instillation of test material,
the test eye was washed with
ML of lukewarm
tap water for &L seconds.
L@@nwashed
OBSERVA7rO N P ER JO D.-
n u r-s
Animal Na.
Location or Corneal Lesions
Ft-
Tail ---- Head
(OCIOR
toGiict (0;@.10 t. 9Lal
Cornea - Opacity Area
Iris
conjunctivae -
Affft
Redness
Chemosis
Discharge
S dium FluoresceinExam A).A
AZA
*'f-Nl
AJ4
Aliq-.AJff Al
lechnician- tr;-Oy@ Date
NA - Not Applicable A - Petite hemorrhage 8 - Blanching C - CTear discharge D - Purulent disch ge E - Hair loss around the eye F - Necrotic Areas G - Un!ti)let.,vnisualize die,*tn severe swelling H - No reactioffto light I Injected
,_Oev iewed By.(4253A)
Date:
J - Corneal epithelial damage, peeling
K - Corneal epithelial damage, piling L - Corneal epithelial damage, pitting
14 - Hyp6pyon 4 Corneal neovascularization P Pannus R Unable to visualize due to
se-,!rtopxctty S Granulation scar tissue POS Positi-vestain retention
NEr3- Negativestain retention
Eye Irritation Score:
I-zt-fill.