Document ZnbEKDwQwGNOpEOY6zwbyRg7J
.
Attachments
Studies
to Letter to C. Auer dated
and Other Information on
May 18,
Certain
2000
AR2AG- 0320
Perfluorooctane Sulfonate-Related Compounds
13. PFOS
Additional Studies on Perfluorooctane Sulfonate
AcuteToxicity
1)
Acute Toxicity Tests for T-T-6684, perfluorooctanesulfonate:
Didecyldimethylammonium
salt
of
2) HAaczulteetoOnr,alInTco.,xiPcriotjyecSttNuod.yoCfHT-W66681410i1n1R4a9t,s3(MOERCefDerGeuindceeliNnoe.s)T,-6C6o8m4iJnagnuary 31,1997
b) GPuriidmealriyneDse),rmCaolmiInrgrHaizlte/taCoontr,rioIsnoci.o,nnPrSotjuedcyt oNfo.T-C66H8W4 6in11R0a1bb1i5t0s,(3OMECReDference
No. T-6684 January 10,
1(9d9i7decyldimethylammonium
saltof
perfluorooctanesulfonate),
)
Primary Eye Guidelines),
CIorrmitiantigonH/azCloertroons,ioInnc.S,tuPrdoyjoefcTt-N6o6.8C4HinWR6ab1b1i0t1s15(1O,E3CMD
Reference
No. T-6684 January 28,
(1d9i97decyldimethylammonium
salt
of
perfluorooctanesulfonate),
2) Acute Toxicity Tests for T-5898, lithium perfluorooctane sulfonate, 3M Ref, FC-94:
a) SFitnuadlyRNeop.or4t0,2A0c0u4t6e8,OrAaplriTlox2i2c,it1y99S4tudyofT-5898 in Rats, Hazelton Wisconsin,
b) HFianzaelltRoenpoWrit,scPornismianr,ySEtyudeyINroi.ta4ti0o2n0/0C4o6r9ro,siAopnriSlt7u,dy19o9f4T-5898 in Rabbits,
)
Final Report, Primary Dermal Iritation/Corrosion Hazelton Wisconsin, Study No. 40200470, March
Studyof 23, 1994
T-5898
in
Rabbits,
3) (ApceurtfeluOorraolocTtoaxniecsiutlyfo--niRcatasc,idB)i,osMeaarrcchh,4,Inc1.9,736M Reference No. T-1388
Pharmacokinetic Studies
1) RDraabfbtisR,epCorotv,an5-cDeaiLalbyoDraotsoeriDees,rmIancl.,ASbstourdpytNioo.n/6T3o2x9i-c2i0t0y,S3tMudRyoefferTe-n6c6e84Noi.n T-6684 (didecyldimethylammonium salt ofperfluorooctanesulfonate, slurry), July 11, 1997
23.
-
L5553
.
Attachments to Letter to C. Auer dated May 18, 2000
PerSftluudoireosoacntadnOetShuelrfoInnaftoer-mRaetliaotnedoCnoCmeprtoauinnds
2)
Qualitative Investigationofthe 6293 (n-cthyl FOSE phosphate
dIniaVmitmroonMieutmabsoallti(scsmtoerf))T,-T6-269229(4n(-nc-tehtyhlyFlOSE),
T-
HpeurmflaunorHoeopcattaonceystuelsfoUnsaimnigdef)onanSdprTa-y6L29C5/M(pSerafnldurLooCc/tManSe/sMuSl,fonAadtvea)nbcyedRat and
Bioanalytical Services, Inc., 96ADEMO1.3M, November
[Preliminary] 12, 1996
Analytical
Report,
Report
Teratology
1)
Memorandum Developments
from E. to Date,
G. Lamprecht Nov. 6, 1981
re
Fetal
Rat
Lens
Artifact
~
Summary
of
Analytical
MToendiScparlayDeLpCar/tMmCenDte,tAedrmviannacteidonBioofanPaelryftliucoarlo SAenravliycteisc,alInSct.,anNdoa.rd9sSPSrMovYiHdWedO1b3yM3,M August 30, 1995
Studies in Progress
1) DPerroitvocaotli,veFsec[eNs-EM{eFtOhSoEd,DPeFvOeSl,opamnedntFOMSeAtJa,bo3liMsmStrSattuedgyicfoTroxPiercfolluoogryooLcatbaonreastuolrfyo,nate
Study 1999,
Nos., T-636.17; T-6295.21; In-Life End Date November
T2-47,13129.939;
ST-41,
In-Life
Start
Date
November
22,
2) (PrNo-tEo(coFlO,SCEe;ll3PMroTl-if6e3r1a6t.i1o1n),StPuedryflwuiotrhoNoc-tEatnheylSuPlefrofnliucoArcoiodctPaontcassuslifounmaSmaildto(EPtFhOaSn;ol R3aMts,T-P6a2t9h5o.l1o6g)y, AasnsdocNi-aEttehsy]InPteerrnfaltuioornoalo,ctSatnuedsyulNfoo.na1m1i3d2e-(10P0FOSA 3M T-7091.1) in
24.
:
es35q
.
Attachments to Letter to C. Auer dated May 18, 2000
Studies and Other Information on Certain
Perfluorooctane Sulfonate-Related Compounds
13. PFOS
Additional Studies on Perfluorooctane Sulfonate
Bibliography Showing Studies in 3M's Possession Believed To Be In FIFRA Docket. REDACTED
as.
CUS655
C0o.riBnogxH7a54s5ta nc. MaGDedlBiivs2eorniMe,sT:WLI3305137K0iS7nO-sR7m5La4n5TBIlEdY, MFaadxison, WI 53704
CORNING Hazletor
Sponsor:
3M St. Paul, Minnesota
FINAL REPORT
Study Title:
Acute Oral T(oxOiEciCtDy SGtuiuddeyolifneTs-)6684 in Rats
Author:
StevenM. Glaza
Study Completion Date: January 31, 1997
Performing Laboratory: 33C0o1rnKiinngsHmaaznleBtoounleIvnac.rd
Madison, Wisconsin 53704
Laboratory Project Identification:
CHW 61101149
Page 1 0f29
i FEB-3m07 p Hi ee
(C5656
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coCHwWe6n11o01n14s9
`COMPLIANCE STATEMENT
`Acute Oral T(oxOiEciCtDy SGtuiuddeyolifneTs-)6684 in Rats
This study was conducted in accordance with the Organisation for Economic Cooperation
and Development and PrinciplesofGood Laboratory Practice,C(81)30(Final).
-
StevenM. Glaza
Study Director
ACcourtneinSgtuHdaizelseton Inc.
Date AVA
2
005657
- 000000oa0 mwaneo n
QUALITY ASSURANCE STATEMENT
`This report has been reviewed by the Quality Assurance Unitof Corning Hazleton Inc, in accordance with the Organisation for Ecomonic Cooperation and Development (OECD) Principles of Good Laboratory Practice, C(81)30(Final). The following inspections were conducted and findings reported to the Study Director and management
Inspection Dates
From
To
12/19/96
12/19/96
01/23/97 01/24/97
Phase Necropsy Data/Report Review
Date
Reported to
Study Director 12/19/96 01/24/97
Date
Reported to
Management 12/19/96
01/24/97
Ove K+ orth
Representative, Quality Assurance Unit
31-92
Date
5
005658
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cwenons
STUDY IDENTIFICATION
Acute Oral Toxicity StudyofT-6684 in Rats (OECD Guidelines)
Test Material Sponsor
Sponsor'sRepresentative.
Study Director Study Location Study Timetable Study Initiation Date: Experimental (In-ife) Start Date In-life End Date Experimental Termination Date Study Completion Date
T-6684 3M Toxicology Service
Medical Department 3M Center, Bldg. 20-28-02 P.0. Box 33220 St. Paul, MN 55133-3220 Roger G. Perkins, PhD 3M Toxicology Service Medical Department 3M Center, Bldg. 20-28-02 P.0. Box 33220 St. Paul, MN 55133-3220 (612) 133-3222 Steven M. Glaza Corning Hazleton Inc. P.0. Box 7545 Madison, WI 53707-7545 (608) 241-7292 Corning Hazleton Inc. 3301 Kinsman Boulevard Madison, WI 53704
November 27, 1996 December 5, 1996 December 19, 1996 January 31, 1997 January 31, 1997
4
005659
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Acute Studies Steven M. Glaza Study Director Manager Steven R. Sorenson Study Coordinator JeffreBy. Hicks In-life Supervisor Rose M. Bridge Administrative Supervisor
Toxicology Support Kathy Myers Manager Calvin L. Horton Supervisor
KEY PERSONNEL
Quality Assurance Sherry RW. Petsel Manager
cCHHwWe6n11o01n14w9
Laboratory Animal Medicine Cindy J. Cary, DVM Diplomate, ACLAM Supervisor Anatomical Pathology `ThomasE. Palmer, PhD Anatomical Pathologist Deborah L. Pirkel/ Jack Serfort Supervisors Necropsy
s
605660
CONTENTS
CHW 61101149
COMPLIANCE STATEMENT...
QUALITYASSURANCE STATEMENT...
3
STUDYIDENTIFICATION...
KEY PERSONNEL...
sms
OBTECTIVE sts
TEST MATERIAL... Identification.............
srrrs----------
StoandrRetaentigon.e................. Safety PrEGAUHIONS cc...
----
vn I
HOUSIDG onsen
AnimalDiet
i----------------
Animal SeleancdGtRiOUoPInNG...
JuStffOriSPEcCieas SetIeCitioon n ..........remrromrr renee 10
PROCEDURES...
esses
Preparationand AdminiosfTtesrtMaattefiialo...n............
mm nl)
Reason for RouteOf AAMIISTBHON.
cers
mromrs 10
Observations.
em
-------------------- 0
PAHOIORY os --
LocationofRaw Data,Records,andFil REPO...
rer 11
BOY WEIGHS... PHIIOEY csmsmmmmmemmrmigrmesmsm----------
mil 2
DISCUSSION.
---- ns------
12
6
CLso6l
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cCHHWwe611n01o149g
PATHOLOGY REPORT...
13
TABLE
2 3
Individualand Mean Body IndividualCHICA SIGS...
Weights/
Body
WeightGains
(g).......................... 15 16
4 Individual PatholOgY COmMENLS............eeee ess 17
PPIrOoLtOoGcOoLl ATMPE2R0A6MENtc NO. 1 n s n
19 28
Pr0t0CO!AMERAMENt NO. 2 crt
29
7
05662
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cHCawwesu11o01n14e9
OBJECTIVE
"mTahteeroibajlecistiavdemoifntihsitsersetdubdyy wthaesotroalarsoseustset(hgeavaacguet)e toorarlattosxicity produced when the test
All procedural times presented inthisreport fal withinthe acceptable ranges as specified inthe Wisconsin facilityofCorning Hazleton (CHW) Inc. Standard Operating Procedure
(SOP).
TEST MATERIAL _ Identification "The test material was identified as T-6684 and described as an off-white liquid.
Purity and Stability `The Sponsor assumes responsiblity for purity and stability determinations (including under test conditions)
Storage and Retention `The test material was stored at room temperature. Anyunused test material will be returned to the Sponsor aftr issuanceofthe fina report according to CHW SOP. Safety Precautions `Thetestmaterialhandling procedureswereaccordingto CHWSOPsaadpolicies.
COS663 8
_--
conus
TEST SYSTEM
Test Animal `Young adult albino ratsofthe Crl:CD (SD)BR strainwereprocured from Charles River Laboratories, Inc. on November 4, 1996 (Portage, Michigan facility) and November 12, 1996 (Raleigh, North Carolina facility).
`Housing After receipt, the animals were acclimated fora periodofat least 7 days. During acclimation and throughout the study, the aniwemresaepalratsedby sexand group `housed in screen-bottom stainless steel cages. Environmental controls fortheanimal room were set to maintain a temperature of 19 to 25C, a relative humidity of 50% 420%, and a 12-hour light/12-hour dark lighting cycle. In cases where variations fromthese conditions existed,theywere documented and considered to have had no adverse effect on the study outcome.
Animal Diet `The animals were provided continuous access to Laboratory Rodent Diet #5001, PMI Feeds, Inc, and water except for approximately 17 to 20 hours before test material administration when food, but not water,waswithheld. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere withoraffect the results ofthe study.
Animal Selection and Grouping Five male and five female healthy, acclimated rats, weighing from 2535 t0 299 g and. approximately 10 to 13 weeksofage,were used for a single dose levelof 5,000 mg/kg of body weight. Theanimalswere identified by animal number and correspondingeartag throughout the study.
9
005664
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cHCwHeWn61o1m01w149
Justification for Species Selection
Historically, ats have by various regulatory
been used agencies.
as
a
representative
ofa
rodent
species
and
are
preferred
PROCEDURES Preparation and Administrationof Test Material An individual doseofthe test material was calculated for cach animal based on ts fasted body weightandadministered as asingle dose by gavage.Thetest material was administered at a volume of 5.05 mL/kgofbody weight based on an average bulk density 0.99 g/mL.
Reason for Route ofAdministration
Historically, the oral route has bee the routeofchoice for administering a known amount
oftest material
:
Observations Clinical observations were conducted at 1, 2.5, and 4 hoursaftertest material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 daysafertest material administration and again the `momingofDay 14. Body weights were determinedbeforetestmaterial administration (Day 0), at Day 7, and at terminationofthe in-lfe phase (Day 14).
Pathology At terminationofthe in-life phase, all survivinganimalswere euthanized. Al animals, whether found dead during the study or euthanized, were subjected to an abbreviated 805s necropsy examination aad any abnormalities were recorded. After necropsy, the animals were discarded and no issues were saved.
0
0605665
-_-- Statistical Analyses No statistical analyses were required by the protocol.
coCHwWe6u11o01u14g9
LocationofRaw Data, Records, and Final Report `The raw data, records, and an original signed copyofthe final reportwill be retained in the archives of CHW in accordance with CHW SOP.
RESULTS Mortality A summaryof the survival rate is in Table 1. One female was found dead on Day 7. No other mortality was observed. The estimated oral LD values for male and female rats `were determined to begreaterthan 5,000 mg/kgofbody weight.
Body Weights Individual and mean body weights and body weight gains are in Tabl2e. All surviving animals exhibited body weight gain with the exception of3 females which exhibited body `weight losses of1 to 22 g duringthefirstweekofthe study and onemalewhich exhibited a weight ossof 66 g during the second week.
Clinical Signs Individual clinical signs are in Table 3. Allanimalsappeared normal with the exception of the one female which died during the study which exkibited red-stained face, `wetlyellow-stained urogenital area, hunched posture, tremors, hypersensitivittoy touch, `and tonic convulsions. In addition, onemalewas noted to have a missing front tooth on Day 11. This animal subsequently appeared thin on Days 12 through 14. This animal's `weightloss noted abovies probably due to the missing tooth and is not considered to be. test material related.
C5566 n
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Pathology Individual gross necropsy findings arein Table 4. Asummary report by the study pathologist is on Page 13. Therewere no test materia related lesions in anofthe.
`animals.
DISCUSSION
`The acute oral
5,000 mg/kg.
TthoxeiceisttyiomfatTe-d6L6D8s4owvaaslueevafloruamtaeldeinanmdalfeemaanlde
female rats at a dose
rats was determined
level
to be
of
greater than 5,000 mg/kg. The only mortality was the death of one female on Day 7. The
onlytestmaterial related
missing upper right front
clinical signsof
tooth and thin
toxicitywere in one male
appearance andthefemale
which
which
included a
died during
the
study and included red-stained face, wet/yellow-stained urogenital area, hunchedposture,
tremors, hypersensitivity to touch, and tonic convulsions. All surviving animals exhibited
body weight gain with the exceptionofthree females which exhibited body weight losses
of1 to 22 gduringthe first weekofthe study and one male which exhibited a `weight loss
of 66 g during the second week. Theweight loss inthemale animalwas due to a non-test
nectapy, `material related condition. Therewereno test material related lesions observed at
SIGNATURE
I NW Steven M. Glaza.
Study Director
Acute Studies
enn
Date
REFERENCE
1. "Acute Oral Toxicity," Organisationfor Economic CooperationandDevelopment Cedex (February 24, 1987). Guidelinesfor Tes oft Chi emin calg s, Section 4, Health Effects, Number 401, Paris
05667
12
- 00000 awveess
PATHOLOGY REPORT
`There w
and the
ere 10 rats
remaining a
(five males,
nimals were
five females) necropsied. One female died on Test
euthanized and necropsied at the terminationofthe
Day 7
study.
The dose level, dayof death, and gross observations recorded for each animal are in the
Individual Pathology Comments that follow this report.
At necropsy, the only lesions observed were inthefemale that died on test. The ventral
`haircoat was stained and the glandular portoifothne stomach had `multiple, dark red,
pinpoint foci. Thesechangeswere considered incidental findings and unrelated to the test
`material. There were no visible lesions in any oftheanimalsthat survived tostudy
termination...
Tombs.
`ThomaEs. Palmer, PhD Pathologist
(31-97
Date
(61101149 fr)
010797
005668
13
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cHCHwWs6n11o01u14g9
Table 1
Mortality Summary
Dose Level (mg/kg)
Sex
Mortality Results No. Died/ No. Dosed*
5,000
M
5,000
F
os 1/5, Day 74
+ Superscript number indicates number of animals found dead on the indicated day.
05669
14
- cHCHWWen61o10m1s149 Table 2
Individual and Mean Body Weights/ Body Weight Gains (g)
Animal Day 0 Number _ Weight
Clsies 264 cise 270 CIsiT4 299 cis367 298 C1537 29%
Mean 286
Day7 Weight _Gain Males (5,000 mg/kg) 30 46 305 35 352 53 324 26 346 ry 327 2
Day 14 Weight Gain
334 70 339 6 382 83 3m 74 280 18 341 56
Females (5,000 mg/kg)
C12896 284
ci2898 270 C2905 273 C1203 286 ci908 255
213
"7
270 0
31 2
285 1
247 3
209)"
-
303 33
294 21
301 15
271 16
Mean 274
253-20
292 21
*Gainfrom Day 0bodyweight () Value in parantheses is a dead body weight. Superscript number
indicates the day the animal was found dead.
005670
15
Tubes IndivCliSnigs
CHW61101149
TNMuEormbEbeerOObbueeviaioonn TIOa 2e5w4a0TT3 734563 T7T p5g S 3mBS hT uHmE BRW
Maes (5000mpc)
CIS Apert LS SL LSS LLL ttt r sss
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05671
16
Table 4 Individual Pathology Comments Dose Level: 5,000 mg/kgof Body Weight
CHW 61101149
Animal Number Sex cisies M cis' M cis M cisser MM cs7 MM cis F
cis F C2905 F C1003 F cis F = Not applicable.
Test Day Died Sacrificed
-
14
-
14
-
1
-
14
-
14
7
-
-
1
-
14
-
1
- 14
-- Necropsy Observation Novisible lesions. No visible lesions. No visible lesions. No visible lesions. No visible lesions. `The haircoatoftheentire ventral surface is stained with dark red anddrymaterial. The mucosal surfaceofthe glandular portion of the stomach has multiple, dark red, pinpoint foci No visible lesions. No visible lesions. No visible lesions. No visible lesions.
17
o 0567:2
APPENDIX
Protocol TP2069 Protocol Amendment No. 1 Protocol Amendment No. 2
cwenores
18
5672 a
-_--
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005675
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cCHHwWe6n11o01m149
TPa2g0e693
Jit 1 sActutue ral Toxicity Study In Rats (OECD Gutdelfnes)
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05676
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Laboratory Practices.
F. RAthneeyteunFntinuiasolendretpeosrtt,matuenrlieasls wdiiTr)ectbeeddoitshcearrwdiesdeabfyterthetsSspuoannscoer.of
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(if required)
) lIandmitvsitdiucaattinoonsered ear tag
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further testing will be required. If ny mortality occurs
@ fiior man DosePreoaration and Adatntstration
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05679
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TFi2g0e697 E sOatnttahileyrsstetishoananrmeIu,Fesqcuaeilrcseudl.ations (vhen applicable) no statistical 7. RA'efpiomratl report tncluding those fteas 1isted below wiTl be subaitted. DDPeresoscccreridipuprtteiisoonn ooff tthhee tteesstt msaytsetretmal DDTeaastbceursliaptotifioonenxpoaofrfgiomaernntytaatl]oixtlyicndiaetftifaaetcibtoysn.saenxdatnderdnotsneatlieovnel TLaybuhlecaantlicoaunplapotfiicomnasetenT)obrodeyacwheisgehxtsWibtyh sSe6xk 1cnodnfdiodseencleevIenltervals Gross pathology findings/gross pathalogy report. (vhen applicable) 8. LOfaorcacfccaaeitipiinttoaaalnntcoeedfaoRaafu,adithtoDeirantgcafo,itpnhaRelees'csrotetrpuhdoedrsryts,.adatun,rdWihwFneiinlnliatthlsbeeRpefrapoivogmirrllteasbsrleepaonrdattb1Hesiflorceotmopleted, 3F1e1tsionreidginTanlthepapaerrchdaitvae,s o"fincHlIudicngortdhoisen.gtbieemi: )11S55oend below wi) be Itonastechpeorevpenacrdoartpdirsoontercecosrdesendents OSDboossdeervvaaeditainoinsstration ASFiatnauatdloyaicrceoparolrret"sppaot(nohdroielgnoicgneyalrecsoirgdnesd copy) OThLe fbeollaorrcihnigvedsuwpiptohrttihneg rsteucdoyrddsatwai.ll be retained at WI bat will AHnnaiitnmeaar]larne"arcloeyciaspttts/'eamcpreeelrcaoirtmduasrteioanndrheucmoirddsity records RTnesftrriigseernattorcalanfdbraftrieoenzerandtemmypienrtaetnursencerecroercdosrds
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PROTOCOL. AMENDHENTS
.
Anendsent No. _[
|
Effective _Nownacs27.799
Portion of Protocol Beng Modified: __fsplicable sections oftheorotacal|.
ReasoanndftoorKroedfileicctataioCno:mpanToy siadennetifcyhangthee frloocnatHiaonsTewtheorne Fithesconstsud wtiolel HbeFT]conducted
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oN. Glows PROTOCOL. AMENDIENTS
|r
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--
|
Effective _Novouooe27,1996
portion of protec Beg Wifisd: EPagx 4,6, isDt ecinsAs ,fne) ls|
FP mr morc | [Reason for Modification: Yocorr dent1fy the nomenclature ysed for an
| osetestron artesbiver bortortesne, [Fodttscation: _seolace this section with the tollovize changer
| |
arsour
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005683
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