Document zzr8yM97erY46jNqL919GYV16
AR R26 -- 0667
PFOA
Acute Toxicity - 3
000847
EP HAEZE RLEETE ON
5Karen Armstrong Toxicology Services
Building 220-2-02 St. Paul, MN 55144-1000 Sample: T-4416
FINAL REPORT
3
GECEITY
MAR 51990
Zetic3oMr0%3
HA Wamber:_ s1z01741
Enclosed:
Primary Eye Irritation/Corrosion Study in Rabbits (OECD Guidelines)
o Raw Dats Appendix 0 Key Personnel
0 Methodology Summary of Results References
Signed:
<
NN a MN
Steven M. Glaza
Study Director Acute Toxicology
Ne ~
229.90
mate
eno
GUOETS
. @ HHE aAAZtZE LLEsETSTOaONnN
HLA Number: 91201741
Sample: T-4416
Acute Toxicology.
Selon Sapervisor Steven M. Glaza
Study Director
Steven R. Sorenson
Study Coordinator Patricia Padgham Group Leader
SRehpaorretn E1.sorHeotwmeartyor
Page 2
KEY PERSONNEL
QualityAssurance
Deborah L. Keller Manager
LaboAnrimaalVteteorinrariyan
Cindy J. Cary, DVM Diplomate, ACLAM
J n re g
soompi
000849
@ HHm T AAZi ZLT LEm ETTOe ONN
WA Number: 91201761
Page 3
Sample: T-4416
METHODOLOGY
Objective: To assess the relative level of ocular irritation/corrosion produced following a single exposure of a test substance to one eye of albino rabbits according to the Organisationfor Economic Cooperation and Development's Guidelines for Testing Chemicals.
Test Material: T-4416 Physical Description: Purity and Stability:
Storage and Retention:
Safety Precautions:
Clear colorless liquid
ny unased material wii ve returoed to Sponsor Sponsor assumes responsibility for purity and
stability determinations (including under test conditions). The test material was stored at room temperature.
according to HLA Standard Operating Procedure.
NHoLrAmaSltanhdaanrddlinOgperpartoicnegdurPersocewdeurree.used according to
Test Animal: Adult albino rabbits, Hra:(NZW)SPF, were procured, maintained individually in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of High Fiber Rabbit Chow 5326, Purina Mills, Inc., and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with
SEindards, out] ned In the Cutde for he Care and vee of Laboratory Animals"? If variations from the prescribed environmental conditions GRISted, they were Socumented and Considered to hava me oFfoc on' a study outcome. No contaminants were expected to have been present in the feed or
water which would have interfered with or affected the results of the study.
we One male and two female acclimated animals, weighing from 2148 to 2500 g,
were chosen at random for the test. The animals' eyes were examined within 24 hours prior to test material administration using sodium fluoresceindye procedures. Only those animals with no sign of ocular injury or irritation were used. Test animals were identified by animal number and corresponding
Reraasbobnitforis StpheecieansimSaellecotfiocnh:oiceHibsatosreidcaulployn, ittshe lNaergwe Zoerabliatnd aWndhitneonpailgbmiennoted
Preparation and Administration of Test Material: The sample was dosed as received. The pH was determined to be 9.9.
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000850
@ HpEaoEzseEetso.n
HLA Number: 91201741
Page 4
Sample: T-4416
Treatment: Each rabbit received 0.1 mL of the test material placed into the everted lower 11d of one eye, with the contralateral eye serving as the untreated control. The upper and lower 1ids were gently held together for 1 second to prevent loss of material and then released. The eyes of the rabbits remained unflushed.
Reason for Route of Administration: Historically, the ocular route is the route of choice based on the method of Draize.'
Observations: The treated eyes were observed for ocular irritation at 1, 24, 48, 72 and 96 hours, and Days 7, 14 and 21 after treatment.
At the 24- and 72-hour, and 7-, 14- and 21-day readings, sodium fluorescein
and scored according to the Draize technique.
Animals were weighed just prior to test material administration and at weekly intervals throughout the study.
Statistical Methods: No statistical method was performed. Location of Raw Data and Final Report: The raw data and a copy of the final
report will be retained in the archives of HLA.
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000851
@ HS EAEZE LEETE ON
HLA Number: 91201741 Sample: T-4416
Page 5
SUMARY OF RESULTS
Test Animal: Albino Rabbits - Hra:(NZW)SPF Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 12/19/89
Start Date (In-life): 01/10/90
End Date (In-Life):
01/31/90
Average Primary Eye Irritation Scores*
Observation
--Period
Average
Score
i21HoHofluuoorrrw
4ab#i13e.]0
3o%'fsour
#i3
Day 14
6.0
Day 21
0.0
* The average primary eye irritation score is the total eye irritation score for all the animals divided by the number of animals (3) at each observation period.
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000852
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HLA Number: 91201741 Sample: T-4416
Page 6
Table 1 Individual Eye Irritation Scores
Animal Observation Cornea
Number ~~_Period=~ A B
Score
AXBXS
Iris
A
Score
AXS5
Lonjunctivae
AB C
Score
(A4B4C)2
F31165
1 Hour
14
20
1
5
23
3
16
24 Hour
? 4 20
1
48 Hour
13
15
1
72 Hour
1 4 20
1
dsblhtee o21o0do3 B ho10 208 33ia3f%s0 %3 Day 21
00
0
0
5
33
3
18
5
32
2
14
5
32
2
14
0
00
0
0
F31127
Bus
1 Hour 24 Hour
e hsew o110044f00BB 48 Hour
14
20
i 4 20
14
20
Day 14 Day 21
i1
5
00
0
5
J
5
r 11 1r 1 %5
1
5
0
0
23 33
3131%%2
21 00
aber 24 Hour
14
24
mBayloooo5 48 Hour
72 Hour 96 Hour Day 7
14 14 13 12
m1 sz 3 40
1
20
3
20
1
15
1
b oo 5o8 88oa 10
[J
5
33
s
32
5
32
5
32
0
21
3
16
3
18
3o31 on1o2n
0
6
0
0
31
2
16
1
12
3
12
1
12
8o0 863
Cornea A - Degree of opacity B - Area of involvement
Conjunctivae
8 Bethan. A - Redness
B - Chemosis
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000853
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HLA Number: 91201741
Page 7
Sample: T-4416
Table 2 Sodium Fluorescein Examination
Animal __________ ObservationPeriod
Number Pre-initiation 2H4our 12 Hour Dav7
F31165
NEG
F31127
NEG
F31194
NEG
POS (80%) POS (100%) POS (75%)
POS (55%) POS (80%) POS (80%)
POS (15%) POS (5%)
NEG.
JE - No stain retention POS - Positive stain retention (area of cornea involved)
Day 14 Day21
NEG
NEG
POS (5%) NEG
NEG
NEG
Comments: A pain response (excessive pawing of the treated eye) was elicited in all three animals following instillation of the test material. Blanching of the conjunctivae was observed in all three animals at 1, 24, 48, 72 and 96 hours, and Day 7. Petite hemorrhaging of the conjunctivae was observed in two animals at 24 hours. Corneal epithelial peeling was seen in all three animals at 24, 48, 72 and 96 hours, in two animals at Day 7, and in one animal at Day 14.
REFERENCES 1. "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation
and Development's Guidelines for Testing of Chemicals, Section 405 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Draize, J. H., "Eye Mucosa," In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, Association of Food and Drug Officials of the U.S., pp. 49-50 (1975).
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000854
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PERSONIAICEULT.E SITGOUXAITCUORLEOGYSHEET
tame
rr Becky Beckuith
Anthony Cass
Cindy J. Cary, OW
Kari Gassen Steven H. Glaza Ben Haley
JSeuffreHicLk.s tory
Jin Jirschele
Wayne Hadison
8ud Hebonald Eileen HeComell
Henry Hikula Albert Oleson
Patricia Padghan
Jane Polnow
Steven R. Sorenson
Oa Thieding
Annette R. Turner Lo Rorneze
(05/11/89)
Job Title
Signature
Bolin Lab Animal Technician Bie Leokuiy
Lb fim] Assistant Quads Com.
Lab Animal Veterinarian a)lowe
Sr. Lab Animal Assistant
den.
Section Supervisor es >, og
sr. Lab Anna Assistant Year / oy
Initials
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Senior Section Supervisor (ho @ Nn bve in (gana
sr. Lab animal Assistant Bud mall Bred
Administrative Clerk (32 TZCogn? Loner Lab Animal Assistant ZZ-- zl 1] Sr. Lab Animal Assistant CAROar, JO
Group Leader
Lab Animal Technician
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Clerk
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000857
wa:_912010d PRIMARY EYE IRRITATION TEST OBSERVATIONS
GTTreeossuttp:emy_aet_:e_r_i|Maa:ne Toad (Mashed: a stehceonTdesst. faoylelowwaisngwaiinnsetdilwlaittiohnaofnl toefst lmuakteewrairanl, tap water Tora seconds
_yctmashed
Spservation pertag: 24 Hone
Location of -- [RTI
comes gente
o 2&5
[0i) So [0 P I_ een a T@ o )15% A N )O)O
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Technician: 5,
Date:
[=11-90
YE ACRaIlTcAulaItOeNdbSCyO:RE:Bijkees iOaOtes Veritas bye Th vate
A0h- -peottite.apphleimcoarbrlhea.ging.
XJ - CCoorrnneeaall eeppiitthheelliiaall ddaammaaggee,. ppeielliinngg:.
8 2ClBelaanrchidnisgcharge.
LHZZ CKoyrpnoepaylonepithelial damage, pitting.
0EC= Ftautreutelnotssdiasrcohuanrdget.he eye.
W? Z pCoarnnneuasl neovascularization.
.
16FZ2 RUencarbolteictoarveiassu.alize due to Severs swelling.
7 Z Usneavbelree toopacviitsyu.alize due to 5 - Granulation scar tissue.
W12= fIlnojrecetaecdt.ion to 11ght
N7E0G5 = Naesgiattiivvee ssttaaimn rreetteennttiioonn..
.
GenTRy cere tr 14150
peinAeon RET
Reviewed by
S0 nate:_2-4A
000857
na:_9130014 PRIMARY EYC IRRITATION TEST OBSERVATIONS
TGTeerssottupeaya:et_:e_ri_aR1Tisgi Todd Mashed: unsethceonTdesst.feovlelowwaisngwaisnhsetdilwlaittiohnaofnLteofst lmuakteewrairaml,
35 waterloraa seconds.
_ycUnwashed
JLocatNion oF pacity _ In -- eee--ues
Cornea - Opacit
Tuxes2 Luan [way NX T]| r I l D |N O & ) )N X O O
IN
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YC ICVRaeRlrIciTufAlTiaIetOdeNdByeSrCbOy:RET: gag?enbate Awgeiea
vate:
corse
A8WA=--BpleHaottnictheaipnphgie.imcoarbrlhea.ging.
3XLU - CCCooorrrnnneeeaaalll eeepppiiittthhheeellliitaaalll dddaaammmaaagggeee.,, pppieiteltliiinnnggg:..
0E C CpflaueirarurteJndotsisscdhiaasrrcoghuean.rdget.he eye.
HW? Z yCppoaornpnnyeuoasln..neovascularization.
FC7 hUsenecavrbeolrteeicstwoaerlveliaissnu.ga.lize due to
72 S-
GSUenrvaaebnrlueelatotiopoancviitssyue.aarlizteissduuee. to
i12- TIinojercetaecdt.ion to. Hight.
N5E0G5 KPeogsaittiivvee ssttaaiinn rreetteennttiioonn.
Revicwed by:
Yo Gate 2-5-90
000859
ma:_91a0ind
PRIMARY EYE IRRITATION TEST OBSERVATIONS
[ Test material T-- odd Test eye: Might AnMasuhnestehcdeon:Ldesst feoylelowwaisngwaIsnhsetdillwatiiontanohfLteofst Imuakteewrairanl, Unwashed
tap water forum seconds.
stest .
Location of
Opservation Period: D3
[ues [noo[ugg
>
aw
NT|
)
T-- N cee bess
Cornea - sOpeacit oss
CanjunctiRevdaneess-
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Fes tea tas
X OO
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son ctrescern eal rlpeopled| |N
Technica: vate:
ort sop
EYE ICRaRlIcTuAlTaItOeNdSBCyO:RE: 3pg.ya Date fog Vertes oy TE? nated
ANA - -PNeottiteapphleimcoarbrlheaging. 8CZ- BClleaanrchidnigs.charge. 0E2- ptaulrrulelnotssdiasrcohuanrdget.he eye. 5F2C HUlneacbrloetictoarveiassu.alize due to H Msoeverreeactsiwoenllitnog.Hight. 17 Injected.
X3 - CCoorrnneeaall eeppiitthheellitaall ddaammaaggee,, ppeielliinngg.. LHZ- CHoyrpnoepaylonepithelial damage, pitting. WP C- pCaonrnnuesa.l neovascularization. R - Usneavbelree toopacviitsyu.alize due to PSOS- G-raPnousliattiivoenstsacairn rtiestseunet.ion. NEG Negative stain retention.
Reviewed by:
fo Date: 2-5-0
000860
Group: !
eGo
aif Wasyhpseecdon: ds following instillation of test material, --seztiwashed
Tai) o-oo Mead
7
4
X
-- Rednesness
Le Lae |oo| TIN CYIN
Reviewed by: -
So e nate: 2 2-040
000861
na:_9130114
PRIMARY CYE IRRITATION TEST OBSERVATIONS
TTGirteouetypew: nM|aiTTe--en _Washed:upseThceonTdesst feoylelonwaisngwaIsnhsetdiwiliattiahnaofmL toefst lmuakteewrairaml,
tap water Tora seconds.
_ytnuashed
Location.oF
Cornealeeleestanase
cornea - tpaectity
Dpservatiop sertoq: 2) Dave
[ayes [waa[waa
NT]
NAD
(\|
TPT
TN]
ne
EI
TN
Redness
20 18 |a28
A
meme |1|v[0 TN
Sonim sorescomn elfps APss2 [Ney|
TN
YE IRRITATION SCORE: _1(0
Technician:
/
CVearlicfuileadtedbysBy: "TcZAo~ bDaattee Tyoa: ian
Date:
1-n-40
WRA=- poettiteapphleimcoarbrlhea.ging. 8 22 CBlleaanrchiansge.nare 0 lautrueieJnotssdiasrcohuanrdget.he eye. FZ URencarbolteic.foarveiassu.alize due to W17= fStlenovsererceetaecdts.iwoenlliton'g.Tight.
3X -7 CCoorrnneeaall eeppiitthheelltiaall ddaammsaggee,. ppieetliinng:g.
#L fCyopronpeyaoln:epitheltal damage, pitting.
W7Z Cpoarnnneuasl. neovasculartzation.
7 S
2 -
GUsnreaavbenlrueelatotipooancviitssyuc.salrizteissduuee.
to
N7E0G5 2'FNoesgiattiivvee ssttaaiinn rreetteennttiioonn..
Reviewed by eo
vo ate: 2-590
000862
Gow: ___1
na:_q1aond
Observation Period: 1d Dave
I eee eas IN
X
emocve oe Rednesness L[0o [l aPo2El lPe Sol[TNAATNNTX
oat:
thw
-
000863
na: PRIMARY EYE IRRITATION TEST OBSERVATIONS GTesrtmtoeraw_ : _! Tage Test eye: Right a Masuhpestehcdeon:tdesst faoylelowwaisngwaisnhsetdilwliatthionnaonfL toefst lmuakteewrairaml, tap water tory seconds.
_9120174 _ytinvashed
soto so
Location of
Observation period: _D\ Doss
[ues [yan[yay NT]
T-- ee wea
coms ct i.
ots
| 0 CN l|O o0 |[ O ( a )Na XO HN\ O |) O lolo[a IN] lelo[ol TN]
Ene Roedmnes:s |l0e 0 lloa 0 [laa o |l[Y [| N[AN
wwe |0 {0|o | | |N
sotun ctorescern esse] nets|wee|nies]
[N
Technician: fm
EYE ICRaRlIcTuAlTaItOeNdSCBOy:RE: i0B.0a8te alan
Verified By: apt Dates=1=a0.
Date: y-x-O2 00
ANA- -peottiteapphleimcoarbrlhea.ging. 8 -~ CBlleaanrchidnigs.charge. E - Hpaulrrulelnotssdiasrcohuanrdget.he eye. F -_ Uencarbolteictoarveiassu.alize due to H Wsoeverreeactsiwoenllitnog.ght. 17 Injected.
KJ-
CCoorrnneeaall
eeppiitthheellttaall
damage, damage.
peeling. piling.
HL HyCopronpeyaoln.epithelial damage, pitting.
NP C2 Cpoarnnneuasl. neovasculartzation.
R - Usneavbelree toopacviitsyu.alize due to
P$05- G- raPnousliattiivoenstsacianr triestseunet.ion.
NEG Negative stain retention.
Reviewed by:
arate oan
SG nate: 2-359
000864