Document n9Gn8e4xBgbe723pEM2vEJvnm

TSCA SANITIZED p. 1 A~~ W lesearcti ab:omtories _ ... . . ~-~:. d P:O:.BiDx,178 :Spinrle~s~botiy~; PA;1~968 -ph'~e'~ti4~.~-41:10 fa9t'(215):6364818 Study T146 :: Test .Articlo : -Positive Control : Vehtcte : Author Study Completed. On . PerrEonning Laboratory : MB Research Project # : MB Research Proft0i # : Sponsor ; Sponsor Study# . Citatibn ; 11.O,LUNfE 1, Locat, t"YmPfi . Node ~saY~an M~.oe ~i..LN1~~. AATDID 66~`~'v, E alpha-haxy1cirmamatdahyde (TiCaA}. :Technical Grade 85~o-; ~Ctdtlc~t:Lpt(Ba'tchi:#i~3102MQ DkOethy1 Suffonide (P .,M$+~); Sigt~ta~l.dri~ Batcttl'Lot #04734ME,' . Melissa Kltk f'hP: ; Stui C31t+ector Odober 25, 200? MB Rasearchaabocatories 1T65 ~111e~1~ #~oad Pa? : Box 178 SpiniieMoviitr, PA 't,$988 MB 07.::1:5961 ..ZG 5860M . . 3M:Co~otate~ t'oxicqCogy ~-.-Re~uNatory~etv~ces 31WCenter, Bldg 0220-4t~;E:-03 %1 PdOL PIN 551.444000 01-1:06 Melissa i~il~k, .Pt~.O: (Z007} UM0Bp4Rebs.ebahrecdh~OL-a0l0"i*oar, aOit!odes P~. t :of 6L .. TSCA SANITIZED .. M, 13. R:~ae~t~l~-Laborat~ries ~iaq x~l Rrpje~t:~G' Lfi:~1~1 +G~OD`:l.ABQl~AT+DR,Y~;P~C~C~.~~:~iCQ'AIIPt1~1.~E: :ST~TEME,NT . .. "This ~dyr_wa~~oo~i;dUded:attaUC4r.z~nc~:miitli Gwd :~boFeCay.Fr~o:~:~equire~rqe.nc*~+ofi:~PA: 40 CFR ~f6(1:and .79~,:f't~"~~:~CFR ;;~ .and ~:~p~d.:Rt: ~n'_C3oad:Eabora~rv Oiibueied :i~i ti,e,C~an#~,aon ~on~~ic :Qaopamtion &:'Q"bpmahr-.(OECD), 4W; tft. Ow Test-:a(ticie,;chararizstior+.~.. ~s :pr.~t,fded=4caalki .noi:~n~iuq~s~ijfty~: 1n ad~ition, the te~star~Ge: i~~~iad~an Was-not pecfor~ri,~d:undec<.lhe>~ooii:.'i:atta~atary:Pr~n STUDY DIRMTOR .. . ... . ,. . ;IV1B:~SE7~iRG.H ~ABC?i~ATOf.iIES. Date :.. pholiie: t2!!)M41f0 : : go;2-oj'b2 W: (mysas-Ifsis TSCA SANITIZED MS. Research LabOtAWKIOW oftOJtot NUMBER TEST AR'Fi!CLE SPONSt7R . TITLE M: M.~ I. .. D.. . 5: 6_7._5; : . . . . . .. . . ..... . .. .. . . .. .. . . .. .., . . . 3M~Ct3RPt).~WI.- TE:T-~6G~iLOGY ~ I~EGi1LA10R1~ `sEaui~~s . LocAt LOOP.Node Ass0Y kwo:{ki~ AR,S31RACr - PROTOCOL # : Method ~y~topsis:ApteAminat~S!:~etmeLirrit~Ton soO."P WAS cx0rwduded with-Own tsea-" fAmale s;BAlJ -.itNEe-~ .d~teltnine :~_c~np~tra~or~~of the fest;ekti.de~.:,MT.DID:6~5.~. , in iae vsed in'ttie.deflnitive_Lco~ll :ymph:~d~e.~tu~ly: 'Tt~r{~a~.ltFOecitra~tions:~yb; 5t"i,'yG: .and 10q7a) of the test artiClerwrere1"sfed.(2.aniMals Par group~.. These.con~ertd~ot~slurresponded to apqfaxin~tely'L7o~c-a5glb:1~96 and.2g:~9b ;:of~~F~:a~t~tia r~edie~t :fm~=testarflcie :: ..'fta~,pr:~atY screen. show no ii~itaftan_at a~nX'~f ttte~onoeri~'aiao~s t~ed i~~~. , ;~the,maxfmum:sti~Zzla:c~~.ofi 100/0 . Basd:on these:resrilts,-~atli~.~2~'9~::5096~ ;eriQ ~.OQ9;6pf.tb~stesistbidewen3::Cfios~n .fpc. the iieiMit3ve;. LVmPh (dode~~study by,.t?te;Sti~dy D'vet~oc Fn:4onsSi~GY+ ~i tt5e-spo~~:: . :..: ...: .. Fortliedeffnttive strid "y.;thr~e~sep~icate.:g~aups :4f#~iv`fis~naiiei~C.B~1f~:rpice acumals . per :gmup) were~ :valsii~!:~r~i1g. roup of ;five:tnFce:wbsafeated :vDAIFBO:ari~l ;~nolf~ergrOUP :fiF~ntrii~e,tNas:ueetaa .w~:ttas::pqsit~re cor~rol, . 2596~,'~iCA (irtflM30); ir~ the:a~sntme,mwln~r- :".Tha::ha~v+s. .; . . . ;group..was .kft:unbea~ed ~o .fxovide: .: :. abiass`.eal:iVcefaiei:c.vl~ai("TuFe~s, .e.`. ~at~stsdttaor'tpiic+laevsiod~eu~tciobmapsa,iviesko~~iad~er:tc~arlltrOoil~;~..Oe:n~des;t.~t: w..: ntdrc~o.e..l. :..~w..Q~rorupe;::iadvrhtk~inndl~sfte.itous~-grp recf::bytop[r~l , appiii:ation to the'doisi~:~n'4f eai~.:~*.actce: claiiCy forti~e ~:days fiye;dmai~cs~e~wa:eF.ilroew::i_9n..g.e.tmh. ea..~inr.nF,6riatir:r~Jpeatslet;oenceiadfiAnv,+~ee:Cl;ttmoubs;#pcttfioer-tChoysr~~irdi.finf~~;a::nAattosg:e5-cbr~o~t;;~ia~2e'a~udrei~czayl:a~ttu;.ildiymph:~:.Bnhoddle~)s : were isolated. si!aqle~o~ifsuspen~~ons~~>Iympli node ;cas:(LNo ware -mid ft WC. suspens~an wa$;ai~aij~Ized by ffoiN.cytornetiyfarri3niU_inc~oiation ~tidai~etotait ~ttmbe~of t.F1C.: 'The amntsnt`of protiferataig . (aAtBrdU+) .LNG'vvas dabeMnf~ed as a.~Mtue ~the FSrol'~6er.86,Ve: response~ of.'tt~ia loc~l'Ijrimpli ciade. The stimaiationindex .~Sljyvas'caiculaifis~i-tiydivldirig ;the:pro~fen~ive response,{StdU. i~icorpor~tionj .of eech test articTe:group liy:thec.'pnoEff~atiQe'a~cpon"-oaha:vafi9~clo .Cor~oF grot~R;. .or; for the_14~`ta~t ar6icie:'gPi;iup,: ~Srtiie::prolFf6ra~ve~responseof'the'taahte~cxsntfroi ;~raup.,: 'Testartictes~that' yielded a Sit 0i~ie~ charar.terix+6d as:potentFafly .sen3ldzlng suf~stanoes~ AFtquots .ofthe_ LNC , . . , ... SLSpension: w.e.r.c~- s. t.ai.. r. t+ed-;viritY~-~a(rh'_tio.d. fes-for`iiiirtiiu.nopfienotypirlg :jB :aitid .'T CftIw eyaiuatiori ;_ ~;eU~`w~~ ;wasfiead:,ar~d resuspand~ed in Phpsphate~Buffe.red Balm~s .(PBS) c~antainm~the . . . viet~lft djr ?AAD., Live celtswer~~ena1~ : ..by. flWw cytomeby to dsF%rrnine 9~B'0slFS:'f* cells; and ihe- B:'fcell :ratio. Test.atti~cies:9ndu+eing.~n irra~se of:z2596 (:T.25rfotd).:over .tfie~reh~:(a(:nariieyconlrol in 96:8-oens~or:we B'f ratio:arvere ~cnsidered sensi6ung'subs'batyca~s Su anir~ai in, .t.,;h.e.,A'.f1_t.0.a..:b n~. .?:....% ,d...o. ..s.- .e. :.,g......l ..n~_o:.,u...p.,i :..:.w.. .h.f k, ~_e ... a.i'.p...,ap,.a...h.r..a. se..d.e. e.q,~f.'-ntatuis~sbfeidid:ya:nadn'd~z,feipipbe:iatre:.+de.adw,anCoarnmoagle;ietxiciEeapFtfaorrea:oonne: . Day 6~ of the deStn. itive~., st,,u, .d,~,,~_ . Th~- s. :a:n.~:~c.r, i. ;al`...o,.au. t.,d..:.~~#, .;6e.:.in . ._ . . . : :.w.: lth~BmiU.; saFympth : n :odesvb0ns .not .harvested. Tgrhoeu:~p9:e. rpr.Pa.~o3brseQd+.n:v;.eo.. d.m.-,ii:.~n_e.. ~t. 1.,~.lT_s: .ba.e.r.f.~. em:naiFa~is.Tniqot,., t...S: :e. .l....i... . e. 6._ ..he: ~. <t. i~6e?d;:~ce:alfe~:eOrr ay~~riiih~.titnsa: ls"In W~ 6. to-the~:dosed ears:, . Bod~iweigliEs~siriges were norrnel;.except folr lhe~.~aniRial~n it~e~ iW%~~i~~gfoUP;whk"hN : Pbpqa; (g1.6){i"10 . :. - .. . . . . . .. . . , . . ., . P*0.aot-U . , tBXi (214Q. -bb8~18l8 TSCA SANITIZED MB:. Riasearch L.aboraitories' sct: .~ I~~olocoi .:. m.. .a.07.. 15961 :28 ': F~60M AS.SThtACT :(corifd) sununary (co0it) : IOSt,1_.4 :~t~firts;~rld:.aPP.~.. r:..+.e:d: :em,ar.iated,. :Earsweiling;:rne~athd:andiyjdual.,arnimal otiservaticr~s i~ni'ttdilocl~.ed2.;5l3~tef:nHGo~nk~:. :t:ci~rTats~.1ea.;~;te3s;k-c;`a.drt6'cis~ie~.ttpMi'evaKtiiNrtiaeinits6s'foet~sicu~a~la:+d~attna.=dwTmtakml$r1rivtaaltuieosn" ..f~.,o3t'htew.:StgCotficafhewN1p1O1JSt0W'e6.67~ . : at :25:10: 509~0 aitd 1.006::w~: 0.8; 2,4 at~d 3,8; te5p~liYaly:: 'i7ir~ Sl.:valwe . of 1:00~;MTDia SB~)'5~~pared t~`fhal~ra~ontrol group-~ 8 .9. "t'heae,~. .k. ;.:.af..i:.3: .c. te,.:..e.;l:Vi.;ec,tifi~ilclat-:ofaonktlt;pilr~p;aaeii~ds:sarft~i~ntBioiaeesletso:lfo. f11;rB025=faotld2a5:9l6i.~aQ1 ;: 092M .:2oor:r5i0pNainD~datnodAth9A1 at .10096; ha~ oonteul . c,c. mpa!~.e.. d. .. t.. a..~_.e: ~ok!i~ct~ases~i..g:T~raflo;v~ere :4:04:a1;2~9b,~:1'20 af SO~o..arid 2 ~1 at 100~6,carttpaied to~icte, ai~d 1'.Z~!:ait:t00"!o~ 0uttil3aFeifi to..the-1~Id"`c;ontrol : ODnataskmt:'.TopicaJ a~i.~lica~OO~"of tlae f~t ;arttccte :tUtTD1p 8675, . _ __ .;. . _ ,. at. i00qo (29.9~:~,~:acdirearr~~ein0 resutted in::a:stirrrula8ot~ index greafier then 3, (Sl ? 3)~ as wellas a >2696 Iancct,i~dee~sies..::ai~nd~i~aBrc; aii~lt:~lesrair,~~dtaieni;'t: fh.~etI1~,:~Tt:riaicd~ol.:l~.jmiirpriaprh'Nedodi~~o d:o~tltsis'avyef; i"ifdf+iee atrersdt'naatit3vdeec.olniatro:fas:'~: }Tahetrere!fiEo~Ca3i:svatleuset ;. actiii-e . ngr~dient3:~ B~s9ct oh :ECETOC ciltait,a; the acthre ingred"~entent in MTU1D BfiT5; .ca~~be~ctassiRed as 6 .tiverik: sernsitizer. pt;o~: fixasj ss-6411a 1781~:weikz:~td,`~ost:.c~ta~ " bo7ia7d; spin~er~fio+Mn~.Pals9B8 . i~a~e,4pf 6z. fen (M)MG-1816 TSCA SANITIZED MB Research La_bo~rator~ies Projec~~~ Protoqoff ;~ MA:O7iS9B1:~6 i M60M tQB;IWTNE . _ _., .t,en.~.;a. .l o.,.f. ~ . . ... 5_!.,: .'.a:.:P.., 0". :'..4t."..e.-.s..:.t...,.s._.. ... .. . ~s., . Tfiis stud . .. . . . . . :des. lg~ed: to be a stiend..~alanealtertta~ve::as:say ..faahe-:Bye, t;it8'~.Guf. i.t~i:-:f~tg .._... ..., ..._ _':..`: ;Assaydefaie~ttie :.ICCVAM. rePo, rtt. . . . : :~s8!Ste~r 8.~. . GFR`..~.~4R5~;::auij~: .. .. : EP1i9?~'He.'',kh Ef(eds:T.e.st.i~.fl. uidel~irne;: O. PP7S 87a:2800 final ~uid .eiirn~~f(e~tiv~ Mai~cij:2403;: arxl .OiCQ`T~-~L;!Qi~deline~~429 . .effedblve ;~lpril'2002': ,t1 - identity Taw-CA iticte Gh~ra~teiization Priav~~edby Stsbtfity. DaW Re~ed Stbtne. Deswiptiori Sample Prepara~ion Identity Pr.ovidsd by Date, .Recelved Ezpiratioil D6k6 Sto%age D+esoriptidin Seir%pl0Pr.epata#oa TGSTAiSTIY'i.G ~ : , :.... ... :. ... .. . , . , .. . : See:Appendi.x .K for .T:eK-Arti..d.. e.:Ctiat}~cter.izaliora an4 C,e"Cate .of Map". . : :3MCarporateToxk:ology :&;RegolauxYSec!~es: : NoE .SupPied by the sponsor. :: a7ios1o7 , : Roort1 temperafboa..'Ond humidity : Clear liquid ., . : The test a~~vasa~iIpt. .plle~ `cfu"asseadn apuoous. so. l. uiIdn corttainin; ~9:996 of. ff~e~at~1N8 irng'redie~l , rovas e8-.ceCeived t~or ih~:10tNNot'ratbn,. eW dtiited with the.vafiida; DlrASO,. to appropriate.cohoeritradons^ - : ' : fRosinvE coNrRwL. ; :PIpha~J)exyictnrramaldehyde., (HCA~`ter,hnical Gr.ade 85~16; . Aldtich .l;otlEa'tdi, ~13.1a1?M : dIIB:Reseach l,aboraOr4es MOMS : 1-OW ~ Room MmpemWre, -humidity : iiellowliquld : z 294 N1=of 85.%HCA .was addadio74* of DIlASO; Loylaid a ~5~b~sol~ior, ldentity; t'rovidedBy. ReWved Date EViratloa Daft Sbrage Desdription Sample Preparation pfiorec=~'l9Sj 6364110 iIEHICI:E : i~im~ahjyl : $uffaxlde tOMSO), :Sig.ma~Al~ricl9 Bafichll.ot ~t734ME : M0 Rese"' `~:a~orator.ies : Q4130'T : 04130105: : Room temperature and humidity .. : Clear liquid : Used asTecelved, ~760~sosd;~,:~f+~FtiootITS, .. .. . , :.. _ paI-Ow, TSCA SANITIZED MB Research, Labc~rai~ries s:tuayntta: ;u;M~; . P~oj~t:t:# ; MB Q7.~!IlS6B1:26 Pf+~cW : ~OM Study lnikiata:n.. .. EXperintentat~Star.t Data Experimental:. .,r. erm :[~ate : Draft Repo[t~Sig#.i..e. t. i: 2" Draft Report. Sii,bm'itted Finai Report::Signeii: '~ES`T ;DATES (d. at. e .pnot~l.sigineil~, 0stexposti~e~:;'t~sstsubst~ince) (+ast:ctate::cl~t~:cotiecCed) : {If,appliica:elt'a (itsPPlic": (study comptetjofi);, : tl7/1810.~ : .07M81f~7 : Q,3~tiQ7 : (f9~1.2I0~ . 1.0lD41Q7 : ~4012t~7' EXPERIMENTAL DESIGN "test A. n-t. ~. *.rals,.: ; .. . .. Fernale~i~A/J micew.er~ rerei~ed:frtqt::Jsckson~t:atu~toi~ies;on .0612610,7; 07I10107 :8 0711:T107". Fc~wing equ~Gbr-at~on::p~riod`:of;~:.lea :'flire::4lays; thitly,a~c.,nu~pero..us,. raott-~Pr+e9narttfemale mic.e . ~re: ase'Igndzt to :tt~ .a!P!P~cabla .~rou~rs-e~s~ng sa: compute~~b;tsed ra~'om :r~urimt~er pt,*arn. . .. . . . .. . . ...-. ., .. . -. 7.'he;an~nals:were't~orn on:Q~IQ'~lOI;,Q5,1951Ai' t.q512~1a7,. t~ d.aya, '.T'he.,Dey.1 t:ody, weiglht r~ange=for the; defin'it~re;attid l~ay. t b~djC w~' tile sa~en.:a~iir~als ~xas 19;.3.-.7..:2.O.;g.....r.~n. s.. 'fheweigE, at~rac%aiionoftt~ .ariimalsat .study.:init~donnot;exceed :*2t?%:ofthe -mean:bodY we . .. . .. . 'WTihte animals .ages. wwe.identified::ti~ cpge'ti.otatinp:~nd indel;b1e;tell rnarks,.snd housed- fieage~ in..suspet~d+pd: . 6edc~ng:+~:p~laced::6a-n~'th?a:,~es::and, :-charygect at tea~t:f~ree tlrrresMr.e~: Frash.PMt oOnie::. aE:c::~: ~,ri.Q.ae.0toe~s)f.i:sa,tiwcaFw5retYeemrwp!erte~~et'i;.firneae-icyo~r~~afvtaoil~lte?dt~e.~haatB:a:l~i~t1i~O-*fsi.a,.u~T!h'e~gahntjrls_adea)r'k,rcoyoc,l.~m:.Famndecwaes~-tecxecpttqcstievaenl:yanfodc rriice Vetirtit~'free. .- 'See .AjiWdlsT J for-AnfMala(eaft Pepatt 'pfi*e: .(213)33O4l16 . 'tt4#F~te~a-Q:-l~esCo~flC0-boz;xiII, a-ftW0.Mki,pa18m P6ge .6%ot62 . foat; . .~215) S3Bd89fi- TSCA SANITIZED MB-- ROSOar.ch Lalbora~~orie$ . .. . projaCt`~ ~~wr) - . . .5: ~ .- .:. ~. - M,~~B'~-:~4.-T. -'1~881 .2s' . EJCP'ERIMENTAt DESIGN (cont'd).. Doslng: Irri 6on . r Come (i2. 6~_:.. ,yAj~; Tlir.o. ~: ~raupsofi....C.. S..A. I.J::~. n. k. ei2:aiii~iaiis:-iosrcioun) wer,. e.treafed 6.0kand 1~~196:~ ~ MTDID ron, s.. e.c..x.,,i. t~te d-ays-..s.i.t. . - art~iue.~grc~dient the;fi,_,_. .;:. :tEi~ckne~s8 v.~re'~ari~C:P!!i!~C(::t~n::: 12Q,:hc sthe :f~~.rsl;ds~? ;an~7~ lirs~fEsirtlt~atii ~h~is~b~"?n. ... pesCent?of:d,t~ CD..a;h...3:8f.!a1e9..-8. ..,.i. n:... -~:.`:'.t... F. . ~ ,t ...:..-..,.l ... ~.. E:~_ac~DifBd~uyise-ms~_=c,f!~~aarY.~. ges:ofCrrivi!et1 .i1.~96'wefe~dered... aioiogic~~h~rsign~canf .cb~ed on histaric~iE la>~ora~iyda a~s~nd::~re ot'a:Rq r. esp, onse tD~htei~ri~istiivie'SitCutmdcVo:ci'cf'etr1e~. itas~sito;.ni:Mtc~~seC. ecdOwnac~esntttriaethiioghnessu~sfeadch`iiRe3~hreeb~ttieerR,nanliudtviao~tt LofNtAhSeitUedstX-ewieratt+ceiectaisbsseutpfpslciteddi tbhyat the .sponsor ,, SuC gioups;ofi CBi~fJ mioe , .. . an. lmal~~~r: 9, %.. 4p3v,:ke.te..~. .t~r:sacedd -. .by! . ZoP7c,al appll~,of tt~..testarq~le : . : concecit6ons; . vehir,posftn~ oc~nfrol to the.dorsum ;of e~ch e~ onoe':-daiiq fo~ tt~e oonseati've days (,at,.appmx~mat~ely the sde,oame hr~te.ftct~ day): F~n~erltrattons af ?.~596;.~096 and 1.00% .q fthe;#est_a c2iorrfric;als.e;p~. .asR.n.,,o. drl,: ~ncge:n.tf...o.~a..ab. opnp:r:opiadsm~itvbel:~c~o7.M.r6%o,Eo; r15v!3e6:.hS~ndv2v9as:9: s~pbc::eof~#dt,~eo:a~K!~ttkyte-e3:~~te,netfl~i:odia~.ti:EwSeair'esutrs~cbes:dof.:-#ThFeie."etaeEsAt .. . a. :rnicropipet~a'af`25'isU+arr-r.~ A nal~e .gcoup. Acetoiie;Eyliiii3 0#'4~'f {AUQ) -was no~!~sed of-S animala:wa~asit :~u+treated: 'The .~ao;ia'ck.ot soWb~Y~,Y.of >ie~t:ar,trde defaun venide;. ..l.n_ourlab;a?i.d , . .,., . :D.MSD: ve.t%Mic.::iOld.~::W~ariass:aEnnc+iodiui~ofitac~osreinasisi"tti~~rsr:.t :Trheseu-itts~-svit~~tlticaitiee;:pdeossi~ll. vea~ontrol:.~59-6:wHeDrA~;...praospovsa.aed~~.rvMKiBt,h`abnthdsarp. proir 6,06 "r~ipfrtto-=a~p~ but:no. t'ew~sed fha kiit8tion thr. ~7'h: e.liosing;~uiel~tk~w~;, ; Dose Groupa. :>, Test Sub$ta , .;t._ .~ .:..~ , . Atlirrial ~'s 'i:~ UBtt~;C. ie.--.-. (bM-9E1}. : . .. ... .. . . .. :... .. .. .. Positive'..Gb-:r-..~.:t. .r.ot~-~~2~~ %~H..;C-A.}~,*,..; . . . . 01% 50% MTDaD:8B75, 3:1-~5 100~b::~ITDID 0BZ~,. 4145 T~. AyU.p,. ea.na;imnadl- s.Fi.,rna.tq:h:ueesntcuydyawfeOrbeHe,eeorb+. steontiroendasonce;dar_,l.yti~roug,ijout:tltiQs~c~rfoccliriica.l,:..s.,S..gns..ei,The. r~.. f. local ~mtation. af the<e~Acation sr of-systernie toxioity;.ai~fiot~ ma~talitjf. Bodyweightstiu~er :rei~orded: on Day. "i,..immed~ pcior:bo! das~n,;and on ;Day8~. Prio~ to: BirdU .coo. . ~afme~u~+e. .meMs:were ken from. a1i aniFrals and tewded;ori Do 1, 3j : gnd 8.: jphqw. .('11.5Y:b3$4ft0. 1.T6 s.WOM10id:+postMMW=17a;~ p,ipg:T;pf,62, . ' faz: ::16j~5~18f6 TSCA SANITIZED 8ggqatch .!A S. SbOdY.1W 4NA ?tO BOWIm EXPERjmkNtAL7*ftidN icori0oy Noddi Whiffon and. Prooming" On 0. ho w th'C6. U1=0" sfidft6hW pft*O~~` wem 1~ijecod WM4 460 Amulnelip ~j *"je Ina . -M a-dose-04Opm smu..0,yF. 160 ftiW., ..w -04WDY. m . n n. tDrmml nectpin usffvlaw~ QpOwuo9llifRt---ka-tnf"tO*q-pdatl -PtPiai .tft'!. At.i, bd.- ft'. ropy-mMtA.hyd.M. p. hnod ONA' pr.0 ; A Amd W. th 46-6.. Kvcatm flh : t&%l6ft W.~ IeIre :In:: aiWmIne 4'-u ~ - 'and on lymphooyte (pe RdWe'YtOM ar ~Btdon QkOwsqn, San Josei vlww:Omnl(Obw. m.' a. rgon. m . Ot4 ~nm vi.0~16 mWd-.j f Pb.rDNA and/br OtdU.'.db*WMAhat'hn citimpiVotOWistwovI-.mOuded mm-w-w"Is'MO.Ing gades setan . nteonded red The lheso.aM men mere-armly.;O uskIg COM. Ooest M.0-6~6n bickinw."Imrionoeyiomoy Sysiwmh.-: W.40" CA) . - -- Prdffe n^#4 %w#mnv%K re*mpe, .V VSA)i The:nuold we Oaft . .dtd-'BrdU :*~*~ lqze a On 0 5% -100 WIW~bee_n ippmw *',.4:0-40pp .... we-mhop, Wby, S 6, #6 0 . ~1 .60'wrmse '0bb6d . .. ....... shb.d w9h, WO-gMo. MWn bow p cytomqtr.y., c " ' * wathedind ffib'poil Dm W&Prh-jo.0abib BidU -spe deffin DP IS &A *~" ~-po&offm.bax -1741, *OlnrWkMdv^. 1~1 18M: ps" 8 bf 82 TSCA SANITIZED MR Research I:aboratori.es~ _ . .. . . . .: i~ERt1AENTiQCl.:DE,91!34 (0004 Celi tJumber Detiermir~tiora : Fgi ce!( num4.~... '...d.:e6. errrtiln.atioh lot~'anirriai;'s m~asured atiquot offiiced cslls:was=:t.r.an.s.fe. ~- red;toatite;vciritairiic,i~a~rop~um~dtQe~:, Ttf~niitier:of.i~iisaii.-eacha6q"uot. (representin9 .~.~11500diiu~ionof~lfie ;Lef~tr~bj~'tiow .cytomefry:: " . . .: . :. Ti1h5e0~.t.0.of.(.da.:.i!...nl.u.ut.mbnb: .e.f.-a.r.c. to; of.rc-. =.a..5b0. i4n-);t:oh;~e1: :.~I.Ye"t~oPtha.~i_. ~. o. d.e.v. V. a, .s. d: ~. ..i. ..r. i"ed:.~.!.;..~!:.rt.i.-P. ~.i. n;g :aa.i: i1.) ;:oTtoat:c~f.te::t.:-ettte~J~n~~~rei.:se~.e_:nteed nunribeftsfBrdUf<cells:i~. ;~ Mt!'Ph.:,::.. ~ode . tWal:"i~. st~spensian vras ni~ilHpile~ :bYthe~ Perne~i~ge:of.Ct~Cs:~-E~~ac$d`E- -- - --aha of'.~e celf Eauation 1: (Mean-# ofCe(Isfn AJIqeiot); ~~ (DM*oii Fa*0.A.Totsit-O ot cetis in Node ,. ouai`l-4~; ("I~~I# :OfCetEsirtN4de) :X~ , Celfsl%. =-#'p_roi~~t's..ti. ,ng..-.th. .:-_.. .. .. . :.....-... 1~' : The nieans :and standarddsvIations:vvere;c~aiCU.l~tedfor-eac_h. dve :~rOUp: .: ArlaJysfs ,.- -of, . Stimul. .a..t. ..i:.a.. nandu Dafg: , , ._ . . , . Cak.~riatiohofStim~at rrtr~dex(,$tl: ,',Foreaoh .ar~irryai,:;lymph::n~idet~il :prolifer~tortas :rneasunsdbjttte: nurnk~er,.of~P~altferatiirtg i:,ymplto~y'be~ wasdetetmi~ed i~y:fbw .cY~m~1r:Y a~rrct ihe:~r~ea~r~ SD -then: caicut&t.eavd. for"..'. . .a:- .~'. . ... g..r.o..!.?P~ T.h8:1`nean.nurntier:of..prviife.~.. '. ~.::9..::L`..l!Imp~'l~as'"'~n: each auni~ta. l:~vas it~., . divided3iy. thet~n. nt+tti .of Protiferaitng, t:Yrnphocytes in;ahei:vifiicle.:~ :group: :{Fo~the ;1~0ti' tast arti.c.ie:. gro~p; ihe m. ean hurr~ber.of. .t. ~ro; ~feratfV :_L~rr.. nphoc~was, c[hrided:fry'th~::msan ..r~u.mtier o.f 8nd_lf~ L.NC iri,~e . .naivecanfrotgro~pstrbc:e::r~a ~MS~:w~.;tu~ tn`tf~'dcxse:ptdt?aranforttusgraup..) This "TestX Co 01 Ratro" Is the"Sthiuk~ioA fndex''(S1) ariit virasl :calculaWfor :eactti animal ac~ot~lfn~ao Eqtqatiori 3 hatpuv: ' . r:g,uatiw3: mean *of:Pfoiif~lvmphoOft pefanim i~-. = -Mean #:Of PCOitteFBting Ljar~phnCytes from ~Vehlde vo~rd-group- StfmulattoYi:t~id?e~ 1St)., pr .ariimai . . .. phone:- :(itib7l184;t1 .0 Pe9er .$,cf6Z . hx: (Zt~'f ~536181$ TSCA SANITIZED . p. 10 . ;M~ Researc~t La:bootfiW'`ies. ,. . Stud':-M: p,r~qct:#' Proto~41 :: .I.LNA :-. MB:QT~5981~8 :: 6650.M . .. . . : . .-. . EXPERIME~VTAl.DE1SICiN ('~~t'd), E;C3'caku~attort: u-rule~ion of .. Tk~e"c:oncen~m;at:wtiich SL.~ 3 (EC3j was:caAoutated :atxording. .tathefnlkr~!ing': . Ecrt~: : Ec3: = o+I(3-dN(b41x(Wc.? . s.r. e. :a; c.aii~ the conc:eril~atiorxs ofthe TTeessttHrfic,le :and b,.d are 51 values at:e=h respecttve cwWn"rion . 'ibe skTn , siaMdiza0on potencymn:be classified according :to tihe~folkywing;aable~: ... Ezi~ie. 36_[on ,e. Weak ._ :gg3L%J: . ~0.1 Y-....... ~0:1~1 Z~.<"f0 - - - ~z90=5100: . i . . .. . ., . , . ; -- ... . : ~iR? N'?~ to ~e Decivet<on o#G3 values .. ffo.~a. . Locat lympl:i t~odi DA : C_ ~?.o:. .S. . e: ~R: ::~. . .s:-p. o. .n:;s.;e~.; $:+w. . ._r~, a~Q. .n_P.TSp:.:~.; I.(+.CTs. x:8n9r:9R):, :.J,1., 9~~~(6e'atl~.r~ia8n6:..1<. K.f!i,~e~c: ['at~Tc~:~d. D:A~ BaeiCe,er:..~C- :ch- erni~sl . 47GetbedclG.G~ A, Ry_.en, PM : ~ .~-ad hee~,forev~lua~al. o. . :t.a~. .e. rn. .a. .,~..lre, . , .,b'sldn;~en~'te~[n~;. :Cor hsd,0e?"?eQ~ SQ :(6~2?4?88;.2O,b! Cei~nsYoa' ~COtoxrcologY ECE'i'~::Con ' ~aitd :'PoSdoolo9N~lrG~m~s . EC.ETOG:Tec~niceC E~epat .tlo. :8 . . .. . phcris: :{216) 6*4714 1'7ifiS,iiiistiberoad; ~ofKae bokw-1?8,'.~~tpUu~is~4~;.iis'1SM Pro" .o iffaz fax : (21$) .5'36J1818 TSCA SANITIZED MB; ::RpseaEc~.hzI tabbirailbdn'~o-s 'S.tudy 'TMO US 07-11rFM.WAV41 .26 EVERIMENTAW.bt.010N4. 06 immanophenotyping Ai of LNOf-o1p6pA. ) am *ith . hath werit.Y.. a'bW.ed anil-rW.U" B229 00"Y. (0' . . an nvuse.CD3 OfflibOdy.,g, . . lh Oi mmw bul.1%11r6 Ai "eri : **Shed.AM xesuspend 0 M Pr."ii APPP .k" ;dyqs UWdel y.'tcCdbWWft-%A. -bft -% T cob and.ft WT tOtQm.- raO% Vol* COW OrdtiA., r vwues* tt t1w IO^-t6M wtcle..-gtWO.v also' c.d7mpired to ft riOlve-w group,., Analy.816 OUIMMUMPOOP041" Am~: Inimunophebb m9p .4. 0d lheyl : MU cal6amn a.~Peme. ni" ctliew .. . i6ftb-&the m6an and. % th!e.8'.T:6611'mtl6" (04'usft- csk~Med. *..cfivkfirwo~ft maim 046 calls by-the mian %7 Calls lbr Euuatjipqv -%B22IP4 (8:0611t) MearMS LNO fibm* T r;*rWV- %M2-o+ LNC ftob'Vehiclo Cbritrol GrOup lbjd.ctlw9# PA82-20.+ pelPs. UQqjfiOMr. B-ToWlmtl6,6.reachlgft~uP~s:lm"titOdbY.*-' SA: -Mean .%+ LNOMM.Treated Q.3m n-:w EkTooDraffo 8-.T cst.rafio ftomrTresW Gmmp BT raVo ftm Vehick:Controkuroup : fold Warige MTRatto TSCA SANITIZED MB: Res"rch Lg4o:raOrclhs: Sudy-T~fe . .:. C:i.Nf1 ~?f0~~CL;# : IVfH:O~'=15961 ;;26 Pirotocol :. ~8~0liA EXPERIMENTAL;DESI.ON (Oont'd) : tnte'pietatiiqit;bfthe Data:. A tes~artis~ets consi. der?ed to;ha_ve;a ser~s~izing :P,?. i:enrfat:NareatFn,entre~ulc. 5~in..a . . 3-f-o: ld or ore~ter . . . `(ricrease id ti~s:LN~:.: ptotife.Tia. ...:. {'..~sshQ~a!n,b. Y. :fot~l;9:rdt~+ :aeils)~B1~biveto tiiat:oat.ained i'oxJhe:vehiete ciorifr~t: TYtdreftita;;aesi :atfiCle~,.th~t y;heid'.a S! -~ ~~are.charac.tier~ed -as p.o,onfla~-*arng:substances 1:~f: .ra. :r`. .f:m,e-m:s. .tu.nar.e!. lr~diiq~ .Yhi'a+sn:agrt.dSa.lt>~3c`a:anrrbd:es~unse.idftOia,:?..ndt; ea:.~rrswmeltlnie,.r~tg,ecrr ;~atit~;tha:..dta`tteas't;,nW,tdiicctaeti:.n[sg;: .a s~enosk.n_i. ~r. or urb:.nt -For ~irriri~iuna~lieliotypin~g ;: .incr~s:ss'in .the a~6~ :~eits or8;7 ra~io:ofi,_>::1..26=fold,.:~,?2694~.overuetiicte Epntol~.are coi~sidei~i:l piediCtiare, of a .true seiisifizer. . Fietentjon Of the _DOW: Upon;s. ~~,ing the finai report, `al{xaw data,.;suppor~lng :documlentaaon,~, d repotts a.r~e;subrr~itteri ;to fhe f,.u+.c.-l..i. ivisC b:yt~a-Sttady-Diiectot :-'fhe ra~ d~t~'is ;i~ed:ai fa1B i~~sea:Ccfi by: projept number The ~rial rep,ort is .f~d af kAS:Reseai+ef~:~i spCow, n07% ~d MB project:+nu.c~nb;et- The test :ar~te`A!itl be r.eturrisd td the sulsr~i(tter -. fallowing : subnilss(cn-:ohlie:report . Atnendmerit .ot the Ptcfac+ol : - . ,- .: . .. . . EC3 iwa&,c,a~uiei:ed :~fa;r:thejtest,a :rbcls and inqtuded ;1n.ataereport fie EC3.~ralua~;is :a; repFSSeptatliie of poterrcy.. Ses Appe~dlx a.: Tor proibcp! in ttsentire~i, .. ... , Deviatlons :to he:Qaob.oratory: RraOlces ., ARk-uwu . c,o. r.n..R.l.;e,c.e.:.. .a.est_:. a. r . iac, l.. e-. .n..., nt :provldied to'tli;e.study.direotnt pCi~orto study . t.nft, . ;..--.:, .. ..: -,. . :.: ... , : ., . .. .. corripositiot~anck.ui"tifo~rrii~i::was pie4id~+cl :, In adt!'~aes~,~rt~cle~hara~tes.rzafion,;airov"fided-~y. tt~'~pcins~ar_prior to>sCudy~:~infiiatibre,, ; uvas not cisxc7~dedr,e, ud:r. d~aedr~q~uea,.;b~C.~f~.~r:., ;ti:iai6~oirna'f~onrtjst.;.arPr.drp~ucep~os.e:sB~eofcia~uiss;~stoufdtjhie,.sNOrt duradon;. tne-lnf~rmation provMed +ofiloo ~ox,17$; :w~i!ra~oese,owm;:~.laoes~ PaO 13pf52 fax: : (216)-536-1818 TSCA SANITIZED _. . , I~IB':-~.eso~rctc L. abiQra.~ri-.e,S.~ - .:.~ . . sWdy . Proia0cpt : S~Sp~ RMILT3 .AND DIS.M-0S10N- . . TestActiefe :Fo"lati1o6artd DWng:~ ,.. . . . .. The testarticto ;formed:~a, .hontogenous;,ttZi~hue,;in:, ~e vetiiGe,. , . C?l1pOQ. ..N,o:dtf~itI~s~iirere:ezpe~enced. witi~ the applicat~en of 60 lest aitides~ta tf~e earsa.r wifh the'ref~ltion' ottest aidcles 6.y'~ the eat-surface ":Weigthts {AppendiX Aj: - Body,weiglit.Etiati~we'e-normal; except for the .ari" 161116 1 Ot)6.dose.groupr mbicth lost 1-.4.grarris~ and appeac+ed smadated:. IY~ort~iti;y-aad 1 ...'' . . :Syrsteimt:-:0,0o ~I"ons .(iAp&ODi B): ., .. ,. . ._ .. . :> ~.... , All aniinats survived:ttie,in-Gfe phase of Oh.w. u*iy arid.apppred .no!mal, expe?t;forone .anima.l..in Ehe 10094> dase 9aouP. .~:..~w, hic~ ~l.. . . . . ; ... . emaaated,and:e~liib~te:d. >p. :p'~et"a~.ogen7tal.:are:a!:.Qri.DaY6:of;ti.i~. . . . Glefini#~e StUf~y; 11'liS ~11A*PXa-iCfOUI~?I~d~'n0t:bB .,in~tQd .W~1~. :$FdU.Y's.b .E~37p.11 . ifOd!" :WeF81Mtt8v, I 961."T21e s ns:olis~lvad urthls~aniiral,era.raot .t>citQyed 9roup..appeaned .norrrlai. . to. :be .fest:art~te~ele~ted sirrc:esa. o:~r eriimst~-~ . Eat Svi.r: Rtliteg, _ Q. 'ablia;1,, .Appetdicss. ..C & D.):: , . . , fl prelirimin!Wyi Qermai irr'ftatton:scr!een Was .perPomled .aitd earsv~ltir~8;)peOsuremeritswq%.us.ed:ao assess irritaaon potenti.a.l{See .~kpRet+dix d::for data and`.APpend~c, D::for diagramj:. Ear;~ess: measurements~were:peKormed on .D.ay 1 prior tc. .dosfng; bay-.1 before ;the-third test arric~e.~piication, . and on'Oay Bbefore'saex~as... None afthe conoecitcatim:fiesWti rouded,.It.'incn3ases. : En ear ttiiplcness. . giea~than :~96;:and~hetaforetpr,as :~ot:.r~r~sif.ite'e~d:icri~a~~,: i~a~sa.:on.#~~elfmirla.~Y.~ermai irritafion .acreetr."utts atldaest .article'soi.ub~ .... ..d~: c. i~e'r~ions cits`2596;-., 5096 and. 't 006~-of~;t~t ' arfkle=wece ed for the defiqitive:.Loeai LymAh. Node Assay; TTmese coi~en6ra#ia~sccirros~ld~d to apptcWmately 7 5%;1 .5.r6:and,29a99&<of'the-actireangr~ient'intha,:~sf artide... . : . .. .. .. . . .: ~ . . . . : , I n the defnitiue "y, none of the M~'DID='S6'~5, , , , . . . ._eorloenti~aqons, tesied resu~d in dermat-mritation. Tiie po~ftive.?eontrol, 25I ttCA: t~ad a~greaterthan: 2596:irterea$e in earsw.olling_on Day 6; which'fs tonsi.stehfiitr"ith tlieftaC.ure tiis~l:resuits:anid based on ots .g~en~erat:exxperienc.e opciarsin aboiut`90lo ::of,sttld~es.when. usutg 25.,~ HCA:unthe~vet~ccle DANi$O: : Te>~: r~esutt'is consider~ m~1dt,y td rnoderately inttatirag.: r>hohs: t~ats~tio .. . ... . s~+-seeo;,~; paiasss i~:la:oi3u: . '- >~: {z~sl aas-is.is TSCA SANITIZED MS: fitesearch I;.atuOraitod" stuay-..~ :: .urw~w. . a~r.~e~ec~ :: wtB:oT-~~~~s P~'ot~DCQi :: 565011ft RESUMMANO ars+cUSs100 (ooriea) TsEblw9 : :Ea.r;%wa8ittig Treafin" . *.~_ ,. .. . .. . . . .N. tbanT~tThi~k..~. ress: .~; i,.~.n.:t::. Pre-ctodclrtg 4$ ~1t . Eipd3irl3le 4 Do .:6 Chah e: - " ! Q.aY:8 - ; :I*.9: Day-1 I ', .Now. Q.iB: '0:48. 0_1S d:0%. d.0%- ~ . D1111SC1'(Vehk*A 26% liCA-(Posithce. Conhnl) ~;.,d 39. 0:20 0:2d . . : 543.i; 5.396 Q~24 _ 0.26 _- 26:3~!''0 38:8!0~ 0:10 0:20 : 0.20 5.396 -:6.3% 60JaMT'DID6575, . `i0d9~o IN"T'DiD"8575; OAS . O:2Q _ 0.20 41,!/0 11,1% s a:= . a::te~~:subdance :Isadno. to incne~ses in ear thkkness ~t greate~ ~ian 25y is con*ered lTritauting b_= cansid~red:mifdtyao rt:~terabely:arataiing. phone: : .(2`Ib} 06,i110 Pagel .4of~52' ~ l-~1818 TSCA SANITIZED MB Research Latiara-rto-r-_--.-ie-$-- . . - ., fratocot _ OW)lul aE8L1LT'~ A~N17i: . DIfii~:USSttSN (conYdj ., _ Mesn, Ntimbar Aw Porciagof Proliferatfag..lymp.li.aMode Csils:(Tatile~2): , ..:.. .: . .. . The total nucsiWof prolifeMthS:lyc+fPhocytsav~is~calculebed.by:!~nul~pljrf~g Eotal c,elt`nu.e~ibe~' byahe pe~iceints~e:af the cBAs:that bs~steanccrpoiabeid BrdU. The mean~~otaL.lymphocyte::P.rv(iferafioc~ ior-b of the fre~tent grflapO is ~oiedtn ~'able 2 ; Table l: AN"-df Piropfer~n~ Catis in tlva Lyi~i Nodaf v:tch Treat~ient;t~toup Treatment ,_,. Mafve _ DM3Q (a%hid~}..-2b.% fiCA CposWr4i Cctttrrot)-25yb . MTD~, ID 6676.1 50% .MTD1D6675, . 100%,uTD1D 86T6; .._..~.Ys~hfsf$ . phcns: ~b15si~t10 i+eoc, {21.3)=636-18i8.. TSCA SANITIZED .p.16 MR. Retoar.th LAboratoll'O$ ~RiEsuLTs, AND 1)[SCUSSIOW(cont!d) 100 dphd -(81f(TikbW.-3jAO pohd1OOGE:1'F& :Q* tid, Ord& 'e.1 '~q . th , ._ & . p FO~*tob '1.0 0% tw Cal .- -~-' -1 -*--~ 010' . test As,aw aoWfi groppis.l.he- 006trol ~69 This:Mean 91 W4*4ndard. 0 i I R Or :Wjwws7..a, potentw sonsifting-M.Spo .grao) ... '-' - '* "- * - -''I' . 6A .10U two.up was '(Spe AppeW* I- :W-.kW pyehkiepp.OWgrAo. uP fOUP, w 0 caw166id fT'a01q--!3 An M'k 3., 4y .,dala and:: A. ... ppepOIX. fJ.'b. r. VoAftnent Tat"4: Stimulation Index st .25 26% MTOW 607-5., ~5004 MTOID.667~j tpo 6-1- -2-41- 001d. to.vehide f (4,2.4) Staftocauvelusiftn aft calouIOW 0.vwuekwwawmac1.qby r~rapfiPad i 0Iiai6d .'9: .94f,tVo.t2o.o05o0n,t(h.saetet.. Aw-piprefniddtk". :.tI)h:,9tHyolweeldvaer31. dk .3. .aM CharaMrIzed as potefflial : senskizing, su Epp Cilciblatlon* 'th46EC-3~.WEii~-caiouWtedt6beS.4,8%, . This= PbfWS toaj--cdttoeh#tfibin of iO+.4% .Of the adva, pbQrft. W 1MWE *f- tfb*d, Page 14 qf .'52 : (210 W-1914 TSCA SANITIZED MR, R thLabotatorieS s Prot".0 k0u~x#AND-Mi sCCUISS110"m (pprir, lmmunoph,~natjpfto Oftym pnodit's-ft a AWr 06 (.t experimental DeWgn ;~~on oflft: reW- . GrQup.means;v4s. ..tan4,*d:.- (.S Appehd1x-G.fO'r-1hcljvW.1L.M~.1 daWa.NA *)p onr aM tabufaled below. Tabj 4-.:'Yo JR. P W APP TmaboonK Naive .116m :&0. L25%HCA-(P0dW.6C-QntrQ9 - L 27.1 . 01--Zffil j%WUiD6O76,- jZ3, .'JLgiffl . fOO% MMID OeTA: 1OD%. ::M.MlOW5, 14.3' 01-4 IM (fold to: Wve) 2-30# %CWff ceIlsI Mean.: s;m 70.5 (447' ,73JO: -(-A :t.'O'Y 581 (41" 1 .5y 71t, % M- 7-8) f.82. 1 02.6 62-A (21..8) 5364'"0 HOM - ft= (210'swis.4 TSCA SANITIZED MB-,: :R~saarchL:abQ.rato Study'rfcte : u,NA pioJecE;# : MO,07-11 :~ Amoco : 5$5i1M: ,.. .. ... .. RESULTS ,AND :L~tS~C~l~IOtY .(cor~t'd) Tabte,5 : B:T~l.ymphoo~G~1! R'~tio . .. ... canqd-~ Natv~ 0.20 +t"0: --- dm50 . efskae)- . . . ,25%. ._.HG.i.fc. .(Posfdvs Gontont) ~ 2MMTDiD 88T5; _ ..._.__... . 5:0% M:TDiO.6875:._ . .. :. . . . .,. . : . . : 1OOJo. M1~?iD SfiTS; 10.0% MTDib' 6675,..I Q.46 :"j=6. _.- . _~. O.~IS. . +~ o. 0.17 , +~: o.oa ,._ . 0:20 ~+/-.Mo3 : 2:8" 1.04 1 .20 (foid`to:Na'fiie) : 0:3s t~ :o .o .. 1 .79.. . (fold ~to Vehiole 0:36 2:21# A~=gceaterat~ert ..1 .26=fote! (~26r6 :~c.rease7 osiei vehici~ oontro9 = P~~eaenskiza~g. .re~Pon~o Tf~ e test .. 2itbit;le .: :. eticited-a.~fold . . ir~;creass : . . .. in X,oB ~s~of i,t ;. . . at, 2~~b. 4..22 :at.~~'o: and:4. 91 .krcxe~se of 1:~2,foiciat 10(39i, compared to.the at 100%, naive control, . oompa~ed tb the~netiide cpntrol~ .and,pin Edd ir~a~eS.in ~T WWweoea::Q~t .at :259o,1~ 20:at .,'"af~~`i.;and ~ 2~ at 1p0"6, compared to vnehicie, snd 1..79 ;at.140?~o.:c;cNnpared~ to;tt3e:~1~1~ca:c011tr0~E, phone: i2saf $304110 im.weift r~t.idai*Oo* 178, *On!~~o~+. p :+lam pa~e~eo~sa ;. t~c: {~s~:a~ts~s TSCA SANITIZED MB'Ros.earch LaboW0rrtes $W-.Ysipo. . , ProtoC+oi~ : SBSO.M d6NCLU518N _. ., , Topical Wifcation.;.ot"th~:.;Ee~st.e:iiticIe:MTDlD.66?5 :. . . _ , ,_.ettOD~'d :.(28:'8ti ac~yering;ie~0ientj nesulEsd:..in.4as~mvNaf~dnii~e~ g~e'~ter thari,3{St :>.:~, aswep ~ .a:>2~,~ inereaise`irr:-~b8. cells, atnd in the :B:Tcorirpaired:to both vehk~a~s~ riaive :coi~+ols . TheRetor~ :~iiis:f~st'ariicl"~ ;i~s de(mAJ s..e_n&itize,~.it~ tt.,i..e. .'.aocF!~: Ljrrdaptt .l~Otle`Assay:. `fti8 ~st:at~e h8sa:t~ICtilated;'EC3..vEilu.e.of;~ 8Io (1.6. ..4~b.as~ttie acNve mAcedient~:; Ba~ed:or~ ECETOC :~c~ia; 31iq'at+~ive atgnedieht in MTDiD 667~,. ;catT.#~ classiffed'as ~'~ive~ak sehsitizer . FINAL ftEPORT Appf0V8CI :bY;. . Metissi~,:Kirt~..P.h D.~ Study:Mrector' . D,ate: . . phone : 4?lb}536491 0 . . -170" ~+etfoods.:bffP* ;:boic,97i.<aWa".01, ._ . . : _ . . ~ : , ,. , . 79 of,.6T, .... . tit : (2i5y'R81t4sge TSCA SANITIZED MR Ros"rc.ti Laba.ra,tori.es 1?1ppendiX .A;". Body:'Waighfis: in:girGms sftii;ay~.:TtIA :.: ;u:NR P>ioject:~ hro~`bco.l . x. :' NS- tBQ-6a;~z~M~~,~'8s1:2B ' J1ir4: i 3 4 5 - .. F F F' F MlBAi~ S:a_ :Naixe DW ;. ' . ft B: 19.1 2't .1 . 21:.1 . 22:.0 21~1~4____- 22:5. . 21 0 1.8 l,,T 5 S B. ` 1-.4 . 1:51.0 . 1 2: 0;3. 5:: DNfSE3~~ Ve~iCle An::# S~e~tc .1 : : . .:~_ 5.: B:W:. . -. .. .. . . .. . . .. ~: ., ?' F 20::0.' ;21_.S 1.8-. 8 F ;04, P: :3 1 ~. 9, F 212 02 :70 F 19:5 - - - 2'C-:~--- -----------:;20. i s. ~0:7 ,An: #. '. 'f 3 14= ~5 -26%.MCA-PosifiVe Control -Sex. ay-<1 Da'y~'.8 F F ` F F::.. . IMEA 21'; :3 9.8:;3 20:.,~_ ;3 .... . ,. . .. 22 9 20:~ 2; 2: . ;. 7. . - 'C :4 B:W,:.Chainge ; 1. :6. 1. .5 1 :.8: 1 ; 7: - #: 5 5: 3: ... . . PIfptw .: .~~ .~:~a~~ 4T6S 1~ nPz rc~t! c , PcetofNo~ ~. . 1. . 7. :8. ; . aptiider~toi.:~+ P~ Tow . . .. . . P$g0.20.;Ot 82 TSCA SANITIZED Appendix A(Oo~nt':Of: Body Weiglift . in 04iii3* 77Za~. 731 3233. 3+t Mroio sgxs; . Dr-a - ). E F F F . . .... . 2'~.4 A 2Q7 19:T: .-S,M 0.9 5 u.,re. ', awa~r~e- 22:7~ ' 1, 3 22-2 : 22;1 0.7. 19:8' M,2-. ',~""" _'_'A"l~. ,. .. ... : 1:Z 0:8 5' S 50% (UlTDi0 66*T5;. ; An. :1R- .. 9eoF . . >38: : 3T~ ; F` CSaY.t 39 F. A.0_:. _- , F S.D.; #' i7.8' ~ 21 :5 1.8 5 Day.s.. , ' . . ; . 19:6 . : 24.4 ;~-, 2'I. : ~5 B .N3.-~ 2.3 , . 2.0 2.9 . 0:3 . 5. 900% mmD .6G70.; rV~: ~ "':M.b - - -~ ~. 42 : ~ F 21 .Q .'tS:5 43 F 44 F ..~4.5_..- __ f. MEAN `S :D' 20 .4 ~~ : 'l9..9: 20:8 .4-- ' 0.6 21:7 2Q :9 : 22a ' ,:8: 'fr4 ~ # 6 5 . ~:~ :+t.` . 1 .71 . 1, .p.. . . 1.$ : . . . 1...T . 5' phons;. (21b) b_3~+L710 : --~--- .---:. _ _ M~o~;box:l.2ij ~ :j~+!~1~488 , ~ ' I+.a8e;21 Of= _- :lauc' (24~ :l~35-~SiB TSCA SANITIZED MB:: Re~Of Lab:ara.tor.~~~ ~sw;~y:~t~ Prdj~t~ f~~otacoi : ; u.Mww. : RAB-:tl-7=~5851 .Z6 : 56~OIYF Appendiac;:B:~ Sysf~mte ::0l~servations NWVe-. [TIME. PERIODS:' . Dat1-. Day 2: A .N: 1 M A .L; ... :~ . ._. ~4~F.:. . . .. QaY 3. Day 4. D4 .6. D.ay:e TIME . . PER_I.QDS. DajI:1:. ., ~~,nns_c~ -.._.~_r..,~e ~ {t N:: l 1~1: A . L # :I S E XI. , _ -7F bay_~ Daiy d Day 5 pey8. 25% HCA - .Positive' Confrol A. .N:.1._:M: A C... ....:.#4 3: E 61F . - eatyandli~#as :aninial .appeaisd riorrnai`at ttti2itotiserveation .pailod. . . .... . W~o~,e: (2xs)'s~a~to'~ 1.7gS.Vre(+tz'r~d Pwtt:ofllC4~:bo7r.'L~~ i Page.~i^GT`8Z fa~ .C~t4~1536~1816' p. 23 TSCA SANITIZED , . Me, R"eaircft Labt~ratt~ries: ~rd~ Tlttys: ~~!o,~eCt;~ .. :. [.f.NA; , nns o~-i~ss P~+oibocd~ : 5sao~R Appendi*:B (~rcrnYt~):- S:ystemic: O.~er~raticrns: TIME~ PER ~ [%y~1 Day 1 ,Day 3 'Day 4. liDay S D~y~6 509b MM1D:W7G.;_i ........... ............. .... . A--N 1 M-- A,*. :L - A- l S~ .1~ X. . 311F . 12JF ` - 331F-34iF 700Yo MTDID.6B75; . . TIME: !ERlOD6- 38~F . t- .11A; A r:... . # ,f S. 'E 3F . `. ~71F .. . 3gfF-_ 39fF 401F ~ I; Or :2 ; Day . 3. ,My 4 Day 5 T1ME PERIOW, ,DaYl Ckay~2 pay ~ Da~, 4 W~ S. Day 6 MTDID'6875,, . A:..N , I. M:A1 h~ Cl S-E 1~' . . . 4tiF ~ 431F . 4~ZF .1 . No :erity iiudiceitea arnmal sppeared noYmal et .I* .oQw+uGm pC`iod . . R =.'AnogenU,;ar~ea_ wet Vv'= ~ppeara:.e~adste~! y. _ )te8 sub'stk~.ln:jedinn.ste . ; . ..-, . a?~6.~lld~tda:':pP.#:!p~9 boDc :f7-i, . ~pk~AS.iatcw+R .pa.'l8~6R: . pho~: ~(z1s)~P&4t1o . . , * . fez':. (2t~aS1F?181s_: TSCA SANITIZED esearch Laboratories Appe,ndjx-.ICm P-.j.j . Wry. 0.9fth . .T-mbmnt,.26% MM06676i ~50%Wbld .106%_RTDID WO LM-- WSW moan -airThickhmBlinm). Clia#06 M. D. y 7t)4*, t - D;ky . 021 0.21.-- 510%. 0.,20 04% Vhaftl ISM: fas. (210SX48%. p. 25 TSCA SANITIZED M~~ .9e~earctt. La:l~o.rata~ri:e~ P :oca! :: l,:1:Ny ' : ~Y18t17~1888'~~$ ~~SOl111 ... . ... FiOm QR. .S,eastedan -n?e M,utii~:l.aCeT f:~i~Dh;.lVccle.~flsseY e:Test~Yfethodforll~Q:~lATlst9iGCocfteCtOerrnati~ ~etFB1 :CJ G'Jiem~oalsRCoirqi~pt~r~,~J+~sncf_ICCVAiIf;l9Q4~ .., : iT63i~~ttiiost:~tioorl .& .~R~ :Psi:. pho~e: (Ztb7 3$Si11.0, i>a~e :~b~f i (ax: ~Z96)~"'3E1B : TSCA SANITIZED MB:, :R:.e.s.ear :h: La~x.o._:.r.:a-t-ori~es:. Study.Title . -: I;LMA ------ : a14sM:26 Pfotcicol' : >88EiQ1AA. Appertdfx;E: Stimuiation:index' DM8r3'(1fehiclar) 26%o :HGA {Posiuie control) . 26% 'MrraIp 6e76, 1 2 4 5 lde,an sti)ev- 'Tml:;*.Celis M.NA1d'*M:m. o' 4B3. 2658 1435 1~ 273 .._ 7'86 . 6. T $'. , 10 .: .. ' Mean S'i1?sv 2808 ~"36$ 3829. 84'f 3352 2560 1220 12 . 13 14.: 95 Meah S.EDw! 1, ti 33 34. ._ :M3e3a.n: . :St~lev 12ff12 1'"v215. !2'C42; 1 104 1:'t 328; ~72462 10.3 771 665~. T1 :1 '1ti~E~ 'T6S: T98. : 162 021 O,.dg: 0:39 0: :31:' 0.31: : 0.62~ 0. 66'. 0:?'13. W ;.00,:M38. , : 0.19 1=38` 1.,37: I SO . 1,40. 1;.4'l i 0: 018: i "t.;48; 1.6'I: f ,04: Q:$~ 14d: 'f.~27 A:30. 80$f,~ 0 -7 123.'18; 1,0 2144p., 18 6066 O,d 1, 2730, .. -1.~ .1 ....: . -11.929 . ... . . 1,:0 6181 0.5 'l6f7ki6 ~08~446 21855~ 1$25918 1596$3 ._ 183Q10 28'14B 1,140'T 10D3:4 7394 9~4; 1:1II3Q 024 1000 1.3:9: I7;5 18:3 436 L114- 15 ;3a I 2:4 ~ .o D; 8 ,0 8, 0:,$ 0,$ Q;8 Q:'I 50% AMID 887d5;.. 36 37 3$ 3s 40 _ mean '$tOsv 2298 60'1 1228 469 1371 1'Y93: 729 2 :37 ~~4451 4-6 zs~ 17309 1:6 2,28 2TJ42 23 a.11 9,806 a;a 2.3~ 8'1 .938 27 2:38 28288 Z4 429 'F7010 1.4 a= SIt3 Pbm i"~O 5;tA4?'t0. 17&6 waite road,-' postoM1M b,ow77E: :apimirsEowii;"pa :18961! Pays26.:bf-B2. . .fm (2101836-1818 . p. 27 TSCA SANITIZED M6R"earoh=. Lab0.6- Rrojaci'i~': MBSOMB~07=16861 ;26 6 Appiand.ixf::~ ~ti~nu~a~lr.on: .~iaez:~,cont'd) Tteatmettit 1 oo%mToro_sus, -"" 31 :~89 ` ~ 8: '1a:0.7 1.1:$70 dS?7 28416 . SL Z 2~3 8; :9+e I 5:6 a wS11:3 . ,. . Z = .Aniinal #42 was:bo siek tcbe injedled vwiCt SriiU. .It riraB-SoMflWd :Wlh:ft:teat .of ihp group;. but.nades wqr,e riot takek phqnc (fi1 .6o:a36411. 0: , . P; P`6 -!T2 40 . . : . . tox: :(215):b38~!J8f 6:. TSCA SANITIZED : riltB= R+~eart. h ~abqr s~i .rwe :. Lt_.tA F[o~# , M$ 07.1&9B1 :26 Protoical :. s~50M: Appendix R: ~~m~l.ation.lnd~lc .~s..Tr.o. a#~e. n~k 'L~ai Lympi~No~le~y ~ults: . 8.s I ,I ------~-. . . . . . . . . .. . . - phaYle: (21) S3B~41:iQ'. _ _ ~c_t~.carc~m;-spt : .. .: ...: : ::`ba .y~ tt~ YY81I~~c' . ?aw 2~ ;Of:S2 fsrc: .{2t6~''.t88-,-~818. TSCA SANITIZED MB Reseaarch Laboratories ~ecc~ : _Usi~ay ~MBaSX~a=1sss~ :zs APpendi~c~ G:~ Nartire Immunophenotyping ~ B:and' T .cet~ . . : A~hnal: wt %T' _ 1: 2 21104:24-3. . . : : 7st4.:s4a3,~. 3 1'3;38 fs8::12 4 8:28 ' 7~4.:56:: _ 5 1268 73:Z9= Maaui StDeii: f3:$7-. 4" ;81 ?O :it9' 5,87- SAI Rabo 03.5 020 0.20 . 0F'09 DAA:t0 (Vefikle) `10.2f Q. :?3 7 9:25 012 $ 't1;:4A -68.12 :1? 16 26 0.;24 .. '1:1 .71 ~ i4.7'f~ 7197 : a:~s 2 to- 8 E15 95% HCA (Pbo[ttve:Control) 11 12 13 14 15 Molt" . . 8t Dev :29.:r2 .B~45 2~3_4p MA O 26.59 2T A6~ 2:84 58 ;78 66:19 60:4a 58:.32: 57;6b ~IM 155 0..51 0;47 0; 39 0 52 0:44 046 0.05 2. S'yo l11~1~iD:587$, . 3372. 1248 11.17 14: :84 i2:.;4fl 10:f14 f2,16 . x::67 56tG 1VfTDID:6B7S, 36 72:47 37 13..8$ 0160:19. .38 -1-532 0,22 . 13 .50 0.18 16:54 0:23 14;3'f 7Z.9'1 0:_24;. 1 69 !: 2.79 003 ph,~if~`,{~?~ .bgg"t11Q PO"29 ot.52. . . . . . . : .. v .13983. .,,a, , ; . . taic (ZttB,} :636+t816:. , : ., TSCA SANITIZED MB.: ReseaircM 1sb9r9,ories stiWT1re P'%j~eCt;-# : 3:07-15981:~6 Appendix G; lmmunophenotypiing -B,~rad: t`ceft-(oo~dj . . 400i6 . M'i'610. 6075. 41 42~ d5`: ~ Mom Stit~.~ev 25:8'T Z 2044 : a3.:e3 46A . E48 . 2..9& 69 .83. . 0145 b6:$4 _ e4ss3 ~ 82,87 4;:27 0..42.. Z: 441 OAZ 0:30 0:36 : 4..07 : .. ~=Animal 42.~. 4 :tvo si. ck. t.o. .~iie ,... . in~jected :wift~ :B''d11:: .. if .was~saa~8i~ vvirth Ote .. , nest of i~~.grorip, . but nodesweas notf*en phpne : .(2i.6? 888i110 `f785:yiASTltt..f!bptlr POSta~i*bnX~'!7$.=~6~erst~+te P~'1$~68 Paga 30-4 W . fax: .(21S);bwAb3&. p. 31 TSCA SANITIZED RAM, R~..~..~. -- - -- - - - - ... .:.: '01'-15961'.26." : 56501YF Appen.dix..H:: .ti~t~n..u. n.op~ .t. . +~n~!Pii.i..9:"- B. . :a... n. . :d. .T, .ce. ll. s:. ~`~ts..: Trea~_fim, e~t ~.8220} and 96CD~+ Lympit: Nqd~ Celki Ol,oB C9U's. d9iiT Ce11s ':a8 B 05 :~ 04. -9.' 1-03 ~I s 0.2- 0.1 04 ha1Ya 25% MA 26'%`M1'Q!D BBM _ 30%:btiMW75. 1M MTD1D:98Z3~ Trsatment Mean B;,'T' Rado : #.., 0.As TmabrAwt- ~=:greater 44a-n,L.2. 5~ :~~4 :~.e) over . .. . vehick . .. oomroi ~ poou~,.v.. .aaeeadis7np WN, W:d~efn`i:25X01d .~?~'''X . :f~e~e? cn!e.r.'n~iv~ _-- o~ol..'w.Posfb+'rese~i~n. 9 r!aporrse . ,,h-wi: Ms1.8364ro .t~ t2~a~a:~~a~e p. 32 TSCA SANITIZED MB::Res:ea~'Ch~ Lal~rat4ri~s qpp~ndinl : Staffsticat Anafysis studjr rit<e : ul.NA PnOjeiEt'# : wOT=15m.2B Ptotot~l- : !3850M : _rl~ so .i7tSy,~v~lues : DMSO :f[e:hii":vs,: ' a~so:~z~t,~~::vs: 2s% ...... . - .. :S~ttder~.t~s t-Test : .. ..__._.., .,.,._ Mean Difherame P Value -a1jaoo -- ~1.380: ns ; of 31-values: by Studeht's t:.Tiast ~talve`YS:_ ._.- 100.i36'MTDID :S6T.5 .. ,. : . . : .. ; ... _ . . . :.. . ., .czinfdence) . n:S =. .rnAt :sta~istiM~1Y ~9n .~~~:i1t~~'0.~`) .... phone: {2'f8) b3eN10 1:7d6vie1nft"ro4 Pog9:32.ni 52 iomvwvm Palms faex: O.1b'j 69s-18i8: TSCA SANITIZED +~u~~unr ~ssu. ~reE E. .V., . ALUAMN- ; . . -. 'The Quatiry Aasuraince ;linitah&a i"nspe:d~d:'~ cxWQel.;phsse;;Mahl?s::l~fud~!, audi6ed:EhQ~aw;data.:a:nd:a~:.. . repor~.and .:debarmined :tfifmoaEttthhee :a-~~i.~xatoa!e~ :pr~cerxierd. ;.... aecuratetY:ref,6e~tthe.M.W-data: ;Nc ., .ra~ng :P-..roc~duresvrere :mead~ui. changeslmodlflca~ons proper authorization and ciocurrieiitWon : .Asummaryfaf i,e"Q 0 rtc~1n$pections'is pcesgn~ed : Oate of Pe ' Ka~i.. ~. a;. H. aiAsan, =. D9tleFi1ga Rei~rtatl. to . _ f m-,.m. .t:. . Dii. '101241!~7 101~310T 10124l.07- AD'2= 1Niqiett7f gh:i Quai~lyrAs"Ce .Un; phomr {2i5}:6J64t40 t7s .,enls .osd ; E~oatoiit~ ~b* i~~, spliai~~ovii~% 1ia+sABS : .. Pspe :33 of-82 fe~' C11S~;3.18%fa1B . p. 34 TSCA SANITIZED Appendix_ J MH..:OT,~'Is96'I 26 , ji. .,.a.a.c. ;bkosroatnor~- m~at Health-. Rep.ort ARVEA: ,AX-.9 Repost# 03Q'TAX9 _. . Chectr :oux web'sNe _,.;.;_.._-.._..,~ :.,.._._...:."". for recpnt.upaPates f~s:tltis.rapaFt: httpthaiz;rsi":jax.6rgfneartthlax9:.pdf _.,...._._..._....._...._._._.:.:.`_. ..__. _...._...:..._......_._.......,...._.,__.*,:.,._. ._...._.__.__ C2::rzcei~ec~t: l' no~pcsiti~r~:cesutt's) . .. ... 9` 1~;'OPER/C' ;'Fl3 AS JhAtC: Q`1Ulaziiiwim'barrier R.. .s. rcp: e.. siof {. .P tf~ . 'ite . ~appwri~kr'sCs)- C'1. Good {r~~~.a. t...r..+- e.9ens oi para..sites) D k1tgh Sa"jer W~St,andarct barrier QRes#a.t+cFi S"Eand:ai'da>*rier, Ll~1:owbarriw IiX-S'aS tN; 0 Prosliic3ibn F'-aci.l.,.i..t,y, . . :: C3 ~tessa:rch Facittty C7 Other.qrea: ~ hous+~::brnalt pxoduClu~ty~we edoni'es ii~, a~iti~d :acs irttwuso r: .e. a. or. ~. .~.. o.es'or soii~oes:ofla4Ger :dAe.Nau~d,ai~, f,r,~,dtstAbutwn. _ . . . . . .,.. _ . . . . .._. . . :.... ._. : . . .. . _.:. _.-_, ..~ . ..~. _ Mouse. p.~:,a~;f. i:..o:: q. . ~..i. as. No :. ~Sfi't:,', l. i.(. E. `..i- 2. . :.E. . SUEYS: . _Thes8:o=9?~n,~ .~~p'A~i!~~ :for :~t~anr,i`,a:;~`icantpateratlal;~i;inberfei~etice~;Xese~t'ch . . 1~`'any dfaF~ais~~+isens ;are foundan ~ .dAX:~rioy3s; atYshipments from ihe'roc~ 8~+e~suf5p9nded amt~xstomeirs are natifieif. _~... .__._~:.. .. .. . ._._,. ._._ ._... . .._. .. . . ..... . . .:. .. .. _ .... . _~. ... .. ._.~_ ._., . .. .._. .. . .":. - 4c+~'atliSm _.~..,..,. . Ti~- dtathod MAN, W . pm . `n Sep;406 daitt `06 -.. VIRUSES . ... .~....... ... _ ... . ._ . ....__ C~cttAftt10~3 vi~7rs. -c~vu : tte~syv~s._~ s:6W. M: EusAorzo : .,c :'s^r_- trn. o: 4~ oat fm__Fl .0/21 o~x ona or~~ . rt:,~rs . , __.. seMm _,E:,.u_,s~,A.:.._"...-..r._.. ..._.._, am son= EUsA ar2t ..... AIM a~ .1 0121 .. t~.ya,cr-~c~-isar:.i~itefaw~d~:.daa9oe~naosms-e.~-~.e~vm~_st,-~.:-o(c.-.vc-~tri_un.ts-) s:~it~tn .... s~~ . . . .t;nzyme . . EUsa : . . t1)t4 _ ., _ w _ . -. - - 021 ~- 0121 rAOuse :muiuuev~nus={!,AbnM .~..._ ,.. S6. iW.+ -~._..euSA'~ .._._:.. .~ 0o2`i , 0/2-1 , orli` . . . N: l:o. use:~yt:.?. .m...~: a_vat.t.~. 5 ,:{MCMV;~. _.~ Serxon . _. ..._. ._.._:_ . . .~ "A _;.--- _ .U13.1 - .... . ~. , M4v- a. ..!.i..ra~pa..t3t. is~ :vuus:.{h+~1.V_}..... _._.r...._ ...._... ~ _._-~...:~IS./.l.. .. _...__...__._ ..._ .QI20 tSA Oi2'I_. _, OTII ,-,.,-4a1m,2-4'_ .. . _. .. -..:_. . . . .._,._ ~ a^~.P.r. tsm _ EL - . _ NPnke+u~ri. t~x_; .~~- .ry.a_..,....y, ~vv.l.s.ft~c5t`:.m{t~~7eVj(F?V. M) , .Sc:n. .i. a: r. .i. 5'ectnri: . j ELISA _...___. ._. 0,26 . ..: 0121-. . 0/21 OM. i2AAih..i. . t, l. . ,3'{R~33) ..-- . ._~.. . . ---- , :.._........_: ..:_ _....A.- t7F.b1 : .^ . VI6:~ : ~. .__.. .,_...:~~ .,~,r- ....,... ~ _ ._.. .:~._. . . ~. . . . -.-~ - " ^. .' _ SAC7ERIfr~ :MYCOP.LASMA,~~T~ . : ~ _ _._ ~.CAR sr:.. ~~m. oemrc~ms ,~ . .. ~14, 'Ch"'.._ . . : cmme M :. 0121. ao~,.~ _vroo n~Nte~!. .0~~ . Serina :. . .,EC:IS.A. ._..._ ._..~., .. , -4124 - on.Tt ~ C.7mbar~errode.~Gum ... . ... >: 0105 0/06` r,..._ ~, .- aas _ 0106 . . -.~S"a-i-r._r.~.n.e. l. l.. a~sp. . " ~. . C~n' pe~tforme. . ..~ .,...r....._....T.::. Mesa,ne C;At3re or:,f~es . . ": - _ Senu~rt EL(SY4. ... , ..... . - . ....'..~,3L0_ 5 ~,..., Ol2 - UJ46 ~ :OI06 . oat - ... _ Ol2I ~ aios .._.._..._._~. _0./..2. .1"_".. .. .-- 9/0 6 0106! _. . .. :~ . .. . .... T. he J~.dcso.:n.,;; l: .aw b. orafo,ry .__._.~ . _. - Page 34, oI oz foraddiGorial defa0s regacduig:orlr healtA TSCA SANITIZED . ApPs1* J MB 07;,'9-59.61: 26 : p. 35 ._ ;- _ ,_. :. . . ..P, .".C._ 2. S.R. :.NE RES:U,I.Ts:. . . .. . . . . .. iqnttMf.i'ooel:o~tl,a.!a,inFoti~e:so.t: ~~f',fabressye::aati~ta~txir~sQir;i?S4r.a9aairvH_~S_r:,nG. ;sm: t.a.tre~. . d?:;fp0otietrQifd~aaN(,7~oh: ip,r~ rnen.t_sd~s~p,un theriaroirttitiia~:o+~.re..e.w.rl~ .F+9r~a~:rain..-df:lc~uts:taorr~ieiwe~tasc-;acieeRr.i~oatbilfe+e'~d ; OCganisrrri . ,--FPm-owr~"r-i-s`---,- -- - ~ Roundvaa'rms . . F..ncepba~'dozda'r.cgr+lcull r .1s ._ . `- _ .. 7 . .. 5t : 4._ 1 . . ~ . -< :. - . . . - .: . .. . .." r ~ . .' ~ . ~_ .:_ . .r. .::.~~..._ 0r,o5 ~ .... =0" . 0 . _. .SUDrrM :~,. . _.. . . . , aws..: UM offlo ~..... ~Cawr.n. . ~ ~issrat .. ~OrOS: - - OlQ6: .--1'f~6. .._ . ._...,~.~ ..~._ t~1tRF : y"ix~ibl . . ..., .~~,~ial~fl5..,....._ ..." .. WQ6 -y-0-1-'-Q-6: . .. :Se. ~r; um- , - . ~EU. SA. - -- ~- ~ ,. flCLI . . Opporfunist(c oargart fstns;~- JR0-PGS17.11.~E. R.. ESt)L, .TS: _.: . . ... _ ~e ?+'9~ ~'6J8~%~,1Y : 0~} ~ :~~~.;Pa~!~?9~~t~at-1 say:oompt~ate dtseas~:o.c~~terfere witt~,r~exear"ch under cectakbclci;umawwl-qbs4 .a :qw,.irrurr~rradeficfienttic?e .'~,h.ey~r~o~ :Uotar.~tad:in.,any:'Ptpducltr~rs :area.-~g.osttiire:rpstdfst~geF:F . . . . . iizvesqgatictn ~dest~ned'ao :eGeni~te'2r1J ia~ rrace:. r......: ...."...._._ ._ r.. . .. :. . ` . . .. " :X~, . . . . . . . . .. -.-:"-- ~ " . . _ _, . Bovdo~atia fic+o+, ..x.~. rr."Pt.rce : .. .... _. .....__.-__.. .T:r~b~a :: ...~;_ .. . .. . ; t~ltiur.a . . ?ai.l6.u. ra. . : , ......: . -. . ., _ ... ,. ,.. 0 . .. . Q : . ,, :.,_..._ . ..OJOS: . 0~ (~Jet~swa pvrewnoniser k"* C~tqr_o' 01", ~ ~OlQ6 . ^t~14~ . . , ~,r re~r~e~e - . .. , ... S.~ , ... . .- f~.I~ _:.. ~.~ 01~20t . . . 0l2.1 . :. FaSt~ttI,~AillA puiC(1!1k~!'!YlDM _. ..... ._. XC~hB~' ~fitr'0' . , ~ - 0114?~': -O~$ ". .. - .~r .--" i Fr,ieu4racystls'~t~rktTr ' _lL : . __.. . . ._ .,_._. ....~,~_._ _ _ . ; GYP- . r^resane ~ ~ulAre ."_. . . .. . . ~0 - ~ ~46.~' .Q/Ob~ . .. __._.. ._:~. .~~._. .~. ...,~ -,~. ooa,. o. ..d.u. . . . f _.,...,~-~....r_ _.._. : . , Mob. . OJ4b~ ~ :WOG . . .~.Y. _.._ ...,", . ..... .. ... __.". ... (~~ec-(ie`onpatho~e.z~t~);orgaitistns :~cis.ibr~e resu.lfs.~or'!- ~3~, . . _, . .. '~tiese ,. . ''acu'~s a%ege+~er_atiy vle+Med:;as nam~it.fla~ of~zuce:or,a~, exogei~ous cli1seassornst,ac~fern'!N~1hrRSSasr.vdi, ifar~yalaha~ .orga~rram~;BCefouhdan .aayJ~1?C.l~x~i~;:lf+e(indutgas.~o;eiiin~F~rs:riipiitt;'titit sh p~enEs: arta>rxot s~peikldil~: Kt'e W si?p.: ol-h-er-t-h-a-n-K.-..pn-eu-r-n-.o- hlae T020 . ., ; ~~~: 'C+Rhire NQppatqoge~'ucp%Wam to.g~, lrlt..a e: ww.+^ ~-=------ p.eg.y,"y .~. DBtu~em8n. VA'l0. . ._. . i :~:. . ...u::, .a'w " KAS.: D~Kt3:ICN1 . p. 36 -- .~ ~ Jac-.~s~~z~ x~~~xatc~iyy TSCA SANITIZED 4ppendix J MB;oi.i6s,6. An. ima~ -Health Report AREA: OP~45 Reptart . #050Ti1liP1 .5 G'fleclt atrr we6 *ife;for-recdn-t 0Pdaito Ois teporf:, hftpaljazcnic.~.:jaxc::orgJheat(hlmp~'f 5~s~3 Q:f.zc.~.. f. enC (na.3~Owe resuHs) I~S:u. p~~ ... . . . .- {~-pa_Shog,et~;;~?arasites or .oppo.r~tisul.3t . U Gub'ct {c+o p~+ho~e~s n+.rn. .~!~site"sl . AAPtS tS :QPEfi;FIT'E.D ~iS A: C~~Ma~irmurr! 4a~` ; ,. .0'1.4igh~BaX,rre~ .. . ~'Stanrts~rd'ba~ri~r U _ ;Rgsear+e~ 3tz~:ndard f;~icri~, c CI-- i .o:w_bam.er MP A5-IS IN: 1~. :~,rotluc0ioti :Facllify. . . . , _. . ., . .. . . "1~1he4;3t,'{~. .-, . . . . ~112~n{7tOdUC~N'f,~ C~ .:ftesearcfi,Eaci(trji` ClOtixtz+r-Area'. . . 401ahtS5~:~.1t81n8d:aS~~~ilblit~u8esre9CtIro0S~lIr~SA.t+~CIPS'-Of~lO~{-,4Atn~nd :~iiKtiG.lwCistn'tw~on~ . ....... .. ...~.iii Mou`se . .. ~ h0g'ns -, A: te)niPG(QtS.~, . r,t.m. .-cT.c. ..We. . . f;r. .t6:fd. .J~.1.o:EhS~. v.l..$.J.a.~La.T'.i.$g:r.~~. .i,-f.'. .~.. . .c..a. : n. t~.;i.- an.. . ti.alfoc-iti~tertefeyir:t:. :wilh :r. It-anyaf tlya .~:organisrns . . .. ~le::~d 60*y ..T1A~t rrro~se,., :atl sh~en'tss from 6Ora'-8rac~'susp~nc~p anCt:~us~~arrrers :~. r~#ler1. _.-._p..c..g_ .a~,n.r.: .. sm . .._._ ....,__.~r..: ....,._:..:. :_.. ..:... .~......., x ~'~ r"~- -.-- .^ ..__ .._ .... . ._,_... .._ . .._, - --- .___ " ._._. ..- . .._-. ._. . ._~. ~~' ~3! `.0 . ~`07_~NO_V.":_ 66 , '4`,ug ~dG . . _ . .. -- -... .__.........~ ... - _..- e. ~od .,-._ ._.._.......,_...~,..._~ . - . ...__..___ ._.__ ......r_.,____..__:__.. :...._ .._._ ._..._..:.. Earbrrma W.W-.. .;"aed__utn --HJSA. OI2'L. ., ". G1/2f:_ ~ Q12 1 ~ . ._ ~DVfI,(t't~-e-i-la-a-'~s):virtrs , Se'itirtt - E1::tSA ,.. . _., . ~ lotzl ~oat_ oat , t)l2i_ - _ - _ .-; .: ....._ ._.._ ..._ .. . .._ ...._.:___.: -..- --*~r-um.... _ -. _._ . .,...._. .. _0-121 0. ,2.1 . tf;~:u.. us ,- . . . .: . . .:.. ,.,".-.. S~.-.u. m, Etf3A . _ fl12 L ~ _-X.t::- ~~.-t-C.,,.....~:'...C-;,:...c.y. ~c_.`..c_,-~o.'i.r~'er.""..;~... .. _,-~,.uw_..r"au`sr~'~. ..~s. S~eerntrrr~ .nm ,., ~usf+ _.._..._.._, ._.......__ 0110 - - ._.. or~ .~ ~ _ 01211 _._. ._-._ Mouse` 41deiiavln~_s__= M-. P_i_.V_~_----- _- ~ _:~___ --- -E- LLSA .._.._. .r. - -._..._O.f_t..t.:..:,_.... ......... .:___~. 0/21. ._ ......___.'.: ... : - ._- .. ---- ,~. _ .. .. . . : unn.:7bJsA..-. - ~`i -. .. . . : .__ :.. . . , ", E. .f.,. .ISA" ._ .,: _..._. _. _.- `or .. ,~.e~. m: . ,~+ :ani ~orzA or~l ..~+'r~waa' .....wT!,--.~"^~_ . .. . . , _. . '~ _. ..w... :. :. .. . i.w.r~.~wr.. . . _. , .. ~BtL;,J..r. f,1;`. ~ EU5A __- Re0vlttts'3AMQ! :3). . ... ._. .... .- ._ . . ._ .:... ...~..__ _._........ : .: ~--... __ _ - " ___.. -.. .. .--- "-E.. LM ~ ~..... . .. . .....__-. . .,..,4~'?1 :0131 _ _.Sen_ ctat- twcu_s~~ . .~._ .: , _o,2.i...r,_ p!.2_!. 'tl1.2,1+ O12.lr ._.,_ . .. . .. ._. . .. ......_ . . "- .~ ._ . ,_ .S_A..C~i'.E~~J.A.'.._~-. .`.~-. M.. Y. C: A-PtAS ~ : ~ .m~ ~c~_ ._ .. .~"~. ._,._._.~o~n __ .,_,. ._._- .,.._.__..__-^ _w_. .- ---- isici _ oio614: - aos ~'0oo~. ._ .. _:~._...._. ~cupa-" - . :or%i __ aar on] ~ 1~~.r_r.r.e.b.~_G. .(,9..+-'. .-:r..~.!.,~. ... _ .*.,: . ... ..,_~.: . :.~:_ ..,. .. :._ ..___._....___,..._. 0A. W. 0x0. 6 0r010 Sak. ,r.. .w. .r. .~. et..f. axpP: orfe~s:, . . -Culba: . Oft. "0 _---_ .0__1.0.6. .._ ..._.,_. .,.._._ ... .-...,~_. . ... ._ . ...-.r.. .. ..__ . .. -. : 'The -.taMfm+i uatriatatorY fi(J6'..lil~. ^~tt,B~R . . . $ae ,r,;lulE ;0A609 Q0422-MICE (6423) Pag~e :36!~,l,. .:52 Fuw-~adiiiticiitst .detarls'c!a,yexdi~9 our haat#~, : rrwnitbri - ' fl-or~. !. sco htfnJl'~oairrice .~:a+~lfu~at,~'- p. 37 TSCA SANITIZED Appendix ;aJ, . MB 0?-13989 ..26 Parasites - NO PO.S:I. TIVE _REStUt.TS .. ..:. Aithough mosf pi.lfwise-ur~aaisms l~ave lhr~ted'~b~nGat:~ raus~ .~ss orintli~fets'i+v~li`nesearcXe; ttaey:~rs un~tabt~s irt .ramst faaititiss:. lf Drty:af .tFtose o.~'9;ui~srr~ ;ac+s, feund; :2iil ShiQ"rtr~lS .fJ+r3trF th6 ro0lm :at~f. aUspendBd:2t1d .txrssEomM 2u~e: nOtitiE 0. ;;(. T~St "- Fleas We mite. ..a;.h,.r. .,a.. . _ ,. ~ur:. 1lit. .u:a-i : . ~ , . , . " ~,'S~'au~s: . `.:V. .fsiteld.~ . - P"uiVrotms . _ _ comm 'Vfadual ...~~_ _ . . . . ,. .... . . . ~aPe'w'ofrl~s_ .~ .. .. . .. ...,.__. . ,- ~ .. .~,. _ .. y -~, . .. -_ . ------ i~~:epr>c~"to?tobirctir~i.au~, .- . . ...,.._..:aerurn,~..-..-. ~. teRiA , , _. b. i-ai-y'. 07 ~OV6 dm Qdt~d . . !06 . FeWD7 N*" 'Q . Aag;'Q6: , ,t~6 .*^ . 0106: . .. . 074f . _ . .QM OW 0J06: :. 0W - l)106: UAM ,: ~ ~W: U/K06: .,.~. ~. .....~_.. ...__ W&L .: _ _.. 0121 . OPP~r. tr~.n.,.tsiic qrga~i.~ms:-.NQ-'pCfSf~lVE~ RGSIa}.TS ~.. . .:. . . . . ..- . 'Thess org2srusmsare .geiieraN fintarfer~.r~itt%, cesea~ under csrtairyc,Ir+eiyms.rBUtCas: :e:,g: ... :M~u!~Qa~.''cict ;mice~ Ttroyero:~iot'~tod-ai.ar~y, ;Prq~isr~~:area' ._posttFv~e;msutts . . investaigattdo des~nedao elFintrrate af! i~itected ~: Sh~irig'fi+om tt~. areaaa :riotsiopped . ... ;: . . ~1!ts~y. 0'Z Fels~ ~0'7 ,.- -"- ,.-~...._r,....:, . Nov,. .06 Aag`Q~: TraGhtga- . Ctiltt~r~:~ . - -- - ,.~ . vF~soes .. . -: Murine .r~ainxurcus{~ ~ rvcY.W nr.AS. ~.,:E, USA . . . -N21 . , .- i'at::.:, iadslvurn_Lia. .. .~.u., m. o. . .lx. . o. P.J. ao. - - _ . Tractvos : . 'Ctdtur<a ._.. . - ,. ow ._. -F~>eiWaac:XS~s .c.a_rl..r.r_R_-_--_._ ._,..._._ . . c:i~[;!# . . -ASyR: intaa,gnc ._..._.f.:.~..-.. ..._.._ . _.~.. _.___... . .-.._. Psisurlompnas spp. or e CO we . . :. 000 , {IIp~ . OV6 iEtl4RjjOCOlSCiIS 8~" l3pportunisde.p~otbzo~ ~~~:: foia~a; ..~. . Tmchp$ :. ' . Ctft9 , ..r..__ .... _ . ,..pfQg p~ . . - ~p ot~}L~ - , film .,..M .... ft"A- -- 0 W.V6 .17m -. ~,~_...._ . Vf.06 other (teo.r..tpattiagenic) . organisms .:.. P.6.. s.i"tive res-ut. . t. ..s. . f, .or. ~. t _o..~: .a. n:. .i: :s. . .t. ~t . 'i"hese, o~rt~s 8ve 9en~canY. ~. !ed ai'rwttrntai:t~ of ~--o(, as-exqi_e . imt~6ils w~tfr:#ttle ottio pote~itial ..ld t~use :. disea~e or Intetfere: Witt.r r~+^c,b :. [f am ofah4~o=e,rgai+isms are aolaM 3n: airy .t~A)t m~ise:. tt+a f'u~c~ing is:~ruoted .in iNs ~+aport;.. but . t)irgpnism S- rpte Tdrsted : TOM. ifueff,od T+4cheaK K1eDsielta spp: otherS~.a-n.it. pnecrmors~s. Intssit~e: ' C:uttura- . _. _... ~... or'tei~s _-- . . ...;:._ -.... .... .- ._ .. ._. ._.~_. .._._ ., ..~._....__. w s4S: . . A;ug 106 t146- Feggy J t7arrnsman: V~D:.tiAS,.DAiCl.AkF S,r. Dfrociot; lsboratory Animal Wealtfrs8eti0eS . . . _ ._ .-..-. ... .., . ._...~.. ..~.. .~-.- ..... ... .... ltie Jat~ks,o,na.aDoratoty+ Gd0 Main,i~eeE . QerklatboF; .1V(E:04848-- ,t . . ., . . , . . .~ . . -_- . .. , . . ._. _ PaAe A 9f R: For additional ~letaiit rega~dinaoeJr:liea(ttz rirmtboMc! WWgram :endsmpp~ipgpqlqCy p. 38 The Jack8on. 0-1. y TSCA SANITIZED . APPOPOX4, ms:&46061 .26 kniMal. HOWth~ Report AREA.-AX-9. OW '_WqO sil'o for:rOc*-qtuPdiRte-sto :tftisreP!Yrthttplrjaxmico:jax..orooiaI OVERAU ..."eALTH STATUS .0 Exe-dilldrit '(0q. pftJwO44wlAq) (46 pelkhop!4. pamikos. pr opoodurifty 0: Good '(no pet6wips'ar par4sites) AX-9 IS 0ftWMp-_-ASA: -1__A_*;F"!Vh-Siindard barrier Q Lovy barrkr Ak-q. ISAN : 01~odkoCtIom :f*01Ity. "Otw:ar*"."gM# -rod cN R*14SJ~Aou M"#!C"jw S~ 16-w. demhd rwcc f6f dJ5*jtWtIw TOM og 4~* Opt If~hy :ofth&o D'r;opq. - organsm yes Ohod . Och arG- U806nded.:,and Mgr-Qr7 Dec'06 GPVII go") vfft4 Ho' K4iui_ M. . Z59;um _',EUSA FL11SA EU~ onxn ... .0121, . . Wa 0/21 W` EUSA Wuse ZefuM . ELISA 41-71, W20: lvlou~e 0 n*qa$6~0120 POOur(*(*A%W S-~. 04vm -EVOK: ALIR'- ;~------_00 JFA 0=1 -'W1O~..q.... wl 0120.,...... . 01", 3K, ROW=~JEDI.M rum . M EUSN. 0122- 0)22" . . 20. IV22: 0120 W-4 BACTERIA&MYC6PLkSWC~ : MYCOP-1 aftbaOey r0cfenuum Salmoaellksoo .. wr-MW T~a :...1nSbwAt56Mi .e.. "Otf cw" Law 'SUS..A-- -_- Sd.rbfW. ELI$A. 0/22 M-6 om - 50 OW wo's' 0106, 0105~ ~1- 2I =6 0/21. W06 0/06 sv'106 0/2) 6114 0)21 35~1 0/21 0/06 0104 Thle JACICiOn IA~OratMl 1-600.422MCE104.23).. Pa.ge 39. of82 MIOro- - .pro0,tam . mgarding ourhaalth 'qolpP!A'0 pojl~Y p. 39 TSCA SANITIZED AppendlXJ MR`074696T.26 pamsites - Nq-POMMISMSSULTS Aftuob most of!bW-prpot " .. ' * ia.rmsfiacillubs.-itany of(0644 orgtislw''g are. 46 organism F1084 furfrd0% kG: F ff;16:;=S sornp!o Ust*d . low , MChod . . Fak cuut, . . . . . ... Okoc" -WA-suW...... Ir.aPOAMMS-_ 0, m allrwt Ili Wood coWto". ar.e *(rod;. IN.; 1. .0. 01 - Uir -'Q. - O. m ; FESK 0/06 . Q*A om. VW oft OM6 Sep ww 0106 0106, .0w, oisportunisoc'.orgmtWo- - NO'.POWTOS ftgSULT.S. rhomorgOolsms'_s7re,.1 C" .h ; ^ '" W~lq.etnnmvcq6. yw - dth Organism : Trachea 'Cultwo 1wc feea" or re. 90" uw6i. N. W. Ol .. o. io. s - . o- rc-~a. Im . ' W06 "06 Wo- o. . .~... _ ., .. . Kjobsiol's paeumor"Be mum$ hd 's Trachea Lany. A f-WV OppodunMd.piotWoa jitv, slodfair fracma . 16(0$on$- cufturi (.;Mfg N&O W2 _'0120 .21 qY0.5 W06 OfO6 :w0l10"4 kWoV-Z5 'V0f/.0Vo :0/0~ 0*5 W06- bm: Other (ii*,oosthogbnl_ organtsmm~~- P69164646SU'lfil f6f 1: Or.90nW. n. Ili .e. .o; r...g,anftmt are Ned as normi:' :6j~~ .83 wtorioussmIcroovadsms oft 109 :w no :poJtopqa4o -;*;se dssm" OrIntsYNnOth .~" K~ :1 any Toport 66t shipmonts,aro-n-ot S.tm. organi*m swuple : T4m. mothod . ..PXV7 'A *10"Ol 'DWO6 Sep"Of vjjgook~ spp, .other than K,.pneciirionlbio iritesane; .Cutture or ieass . _ 'NonpaGaogeciic pratoza: . re.~ g ;~ . - ---:ir"stim- " lVAcro .. ~7db 3Y05 3106 'AI{~6 -- Peggy J:..Danne+mari ;. ViUDY MS ; QAQEii~+f . . . . Sr oiiector.i.atioiatOry:AnimalF{aalftServ(t:O 'T`he:dackspn l.a'tiora.taiY fi00_Mfain,Streek .- . ; . .-, . ;, . ~ar Harbor, 14:D46t}9 . , , 1-800-422-AA1f;6 (6h23) ; . , .' . payr 3WAt^ .. . : . . -- For add'~iRnai det~ils .regaric~p.,our'healCh ioi`trlr.in~ :prC9rurtan4 siuppi.ng:polF.cy. see.'hEE~:l~iaxmit,~aax :arallieaNh TSCA SANITIZED ;ppp.erndtXK . MB 11~-158B1.:2B.. t?66r: sW.io4:riet~ao~xR~oiaas>. Spintle.tsRown;;PA;..~ ;896>3 : -taX-(215)..'638~1.$tg . .. .,: ... . rSsT aRrE. .C:i~E Ct~iizacT~Tion.i tMF+aRMATON in ~!P~.-.~..a.nc. ~..s: ~~4.I w:.~:.. .th.: :~.G!c .do.a~hl ..otL. r~.s bWo.'r'rcai %tcttticyd~ ~:sP~t.,ce3n .e~nt.u'itce ye,. . :({3n 1.Py.9t.te't,!~iQut~st:o,r..otrls..~. :. . a. . ct~aracterizatio~.. ot0A. .p63itiot,; 5fi~i5~'lic~farid, Wit ~,~~I~y.. Ttils.d Rlt~t:a~.~es.n. +.s. .w. ed.'t. .l.y. ~a.l: ~. Stu.d~r_ .; pt3o~'ta:~iud :iaF'l~tion:-ar, t;. . %.11be in~clded n,t1~e flrial`~ePofc ;(EPA 40 +GFR- t60A 05 .alixs"792'705 ;FDA-21 .C~ri:R :58.1-~: IO~D' 6,~. . r 1~r:a.a.aa~~,:;t~~+r~a.<~xs~cte;sat: ~Tcie-.~arac~,eeci~abdtl'staould :beper~arntied incoi~piTance=~vittiihe :Goc~d :Any :ex,c~PlioRS .i~i`3tie .GL,P : . . :reqtintam+antswitl:tse~nt~cated:a-n ttie:Carf~fiaii~ :Staterrrerit oflttie 'lli~ii7 ieQ:oR' Accaidr>gly; ple85e:supply ttie.;`!'olio .wing'3nforrt*orn for:~ tesi.:artlcleaubmitted: T~t:Attic~arleijtlty- : S~e~igch ...., ..,--. ,., PuriEy . ~ptrspo~it~oi? SSAbiGfj~. ~j~i#GCrRKY : -: Trus-Cbaiaderizatf!on Ms conducted under GLPs `or, j , 7"W chairacderizatibiri :%%s,a condeicted uitder Gt3?a SY' Oiqnseuea? r -itcorripa~y) - T :%MARKETINCSTe!!oiste.i!~t`-TM INFO FORM OW paer4 .G .otE2 TSCA SANITIZED Appon+diXK: MR 07-15961 :-26: 3M I .~ ~~09~1'12040 CtitO~rx~ taboiat~~ CeFLI&BtC OiA:21~ .ct::: ~: Mi~D~:066]S: Pr+od~c~:~Tris~ xL.~ . .. .., Bt~,.t.t, ~ ctpu. :.. a..n, d :.. . colorlas~l,nq~soqusao; _.. ... . I :. ~dud~Zals.oa:~~o:~ea~nae.~raeb~lutis.vowg}rt :poc"~oq~aenft~s"nfx~4.~dT~nal:prodii~t .er~dao . ware:dot~tvod ~a:`d~a,caal~medaRC;~!Nt3anii~twfR~lys~a .anE~i~d betaar :. TA$I&I_ smtpw. , MTD1II #6fiT3, . ~aA~a~obsl ~i1ts byl:t+rt~a~-eud 'E~vU+OL id~e~ed Cornp~at~bs'~. '<~~~~:~:.-.~'~~.~a :~ .~~~ -_ ~.-- T;;~~ - ~*-- V.9~* OAK , _-0 743 *O OQ7%- i> .Q3S+F *0..dOp6.Io: O. 0Ol~'*`.0 :0W39b ; ., . . . ~3,as~m~ed.ya.bc_sbt;ca~tonlbc~'ppqpo~es, . . Tma~ed ooonpon~es.wa+e.ab,o_aderoe~ :tod-inxiio "~%Fti41R'spoetra Pap :1. ofl ffltlte.taetxa.~ 3Mi0D: :AWytieal t8b2iia`tiiry Request ''~adY~ti "'of~3R TSCA SANITIZED Appendix. .L Mt3 .07:1398f :28 NIB RIM EARCH LABtJRIA,TOFt~ES STANDARD PROTOCOL 5,6$bM: . . . _ ,. . .. . 1;0 TITL bF.STUDY:: LOCAL LYMNW tJOOE..ASSO LN M1EE (LLNA)` . . ., . 2:0 0.131 C'r1y1? : ...To detecmi~eaQsens'ltizing potentyaai .of #ot?icatiy appli,+e fest substarroeB;. ~'1'f~is t*LldA~irotocai, .modifled [~siRg.flow cyt<?metry'~ariatysi~, is ddsign~..i;.o:b~.an,~tiema~as~ay for the BiieFiterrfeafllg;Se.ns."~izoitzofi.A$say,'defiined,.ihthe IcC,~-.AM :rc .rC.(83;CFR 37`4Q5~B; .f.uly ~f;0;:1t~8) and:flle;LWA as:defiinedIn,:EPA~4:P~'TS.6.70 2QDO; FanaGGuidel(ne:{I~arr,h 2403~; .and: OEM-Test~.u'rctiine'~4285 effec~ve.,Ap'i1:20o2. 3;0; TEST`:AR'fIGLE: . .. . . sp~uonso~:t^.As.i-~:io'utle.sd.tparrtoiv,&deI,es~tweisHt~baeutskriieppclhiaerdac.tbyer.tihzeatsipoonnstoort,hePSritourdtyoDiinrfeflcattoiro.ntotfiia~tsrcei;asutludc,ty';itndhped,e, it Le~ctialica~y fe:ast~e, tthe:name and.quanti~es;oi"urakrtown contamtna~ arid impci'itie~s.. Referi'to se~n-13:.~4 :3:ctfthis protoooi for adifitionat in.formafior) . .. ., . Each teat~arbkk;w111 be ident.,Nfedby source, name, andloc.+ooda numt~er, date :o,freoeiptat iUtB.t2~at~tr and MB PC~ject Numb~r . . ,: .. . 3,3:: :Tt~e :.testatt~cle witl:be stored atirbm temperature and .-hurhtditlr qn.iess otherwise spe~ by the Sponsor : 3..4:: t_Jm'~~: :Sased!~on:fJie.:irtfonxtati,on,provided by the.Sponsor, .appropriate routine safety pj*cautitSns w4tt.t5e~exera'isAd te:ilielienxlting of the:test ariicla :. 3, 5:: : Yehtrte: Ae..necessary.,., a;suitabla~ .v.eliicle.vrifl be added. to the.test`article ;to generat dilutions of tfie`test articie, 'The::aiehicle will be:A40::(a0etone,:o6ve:ail, 4pnaess cthe~se dir~sated by the S~iotisot W!C1en:a ~ietiiete or.~lilcaerit..olhet thar.a A00::wfll be used.~'itmustbe one :tiaat dQes not eI~iCany sigfitlicant'toadC_affOcits:and does.riot substandatiy alter.the ch+emica! ortoxicotogkad propr'rties :aftBe tesE.articlae.. Solubifttjt'tesllng AM the usa;efrre'h'ictes other than AOO, :wJtl~be documentedlet:the.xaw:zlsta. ... .. . . .. . 4:0 (3ENERAFL TfS~'~YSTEM :PARICMETE-RS: _ _ QUANTITATIVE 4 :1 : AnlrrWlltetiWrencents: 1ftRlTt?cT10N IAIRITiATION PRESCRt_EN TEST (it' needed) 4::1,:1: ToiaAsrSnber:of:Aaicrials . 6atleast 12 ' MAIN. My, at leastr25 ~:~1::2: : f~iumtiar o~ ~roucas . atleast .6, incfudirig rtne(t). :con#ol'gr.*up receiving vetifcie.:dioa>e and (1:)..positive.,ccinttQ(gmwp,, ptumat least. thr.+ae (3)test 9rcups receiving cons.ecutive . concentrations 4, :1:'3:. Na . An1m2ilsKarouQ 4..1 ;4; 5uWesJStfain *116. Age . af :least 5' {ail female). . CBAIJ or GBAJJHsd . 842 weeks: old at study iNtlation.{age matched +1- one weak) 1785~weh. .t. z. ... ~a. .d.:: .:.P. ,..o. :. .box.1t8; pttone; .1216~:53$~411,0 Paye 42`0! 52 splnneraLoxq~::~!:,. 1. 89.6.8. :. YaiC(21.Sj 3~'1818 p. 43 TSCA SANITIZED App!enciix L STUDY TITLE: L.Oca) .Lymph- NO&Assaffn ML-8 (LOA) 4,2': , ju 42- 4~ : an and &mber-OrAnlms1s:. LLN&OW . LAOS R ,.-0. . 10- owm PA09 NO:4-OW-A! !fna-M~?p, eomf;.:.Osyherw -djffW*nwc--~ Abe.'LLN .re..WnSe:am 4,22- kW~ 1~4PMWC61'uf. ~Y.our-o:ad.tk(e~i2,woo'k,',pld)~!Wne~adM.'-.-~.to!).-ok.e..- !'Femele., ;CEWj Cd"j~d o~:COXW &*aln m are ocoptablejas, Per..'..0.. .e.M3 And-Ep tqm ey, "diWeytd .,..oompambtereop.oiys.m- The.sciume and strsiA used witF be irtdicabd:in the study t806rf . 4:2 :3: NuinbO;of AnitnA .. 4 2:3:.1. Irriteti~_P~n_: , The Bir~ayse pn~n Is"the r~inimum,nuntt~er need~ct to . deYer:~in~'ifttie'ifttie tint artide hasdermal,mitaflon;propeities at the;higfie:st~at(aino:bts . t:oridenftWri(mofttm,sptS:t471ity)31.1.the vehlC~: . ,., . ,.. . .; . , . . . Tfis 4p5onal Quantilativ~d Iauton ~FesE j12 Mice) is used . . when cri`ta:pn~nt'and .the Msaxitnum apdepta6te dosihg cssnce~s?rteed to be:determingd. . ' 42 3:3a : .~i I1;e$=: Tfie~Mihiirmam ;oumtie,rof.aninaalsin ft:defhiitfvetestls~6;an~~~f5 irr~ati~;;~s:.present a~ ~ ' .' . : _:2 Veratrne~t~ro~i~ i5Y1~~~~~!Y:~ n ,:: For s~ciad~yr.-vet.~icfes~onxnitafions,. a..t~alys;; _- ,. . . . .9. . . = may . needed :_ :T8eal.t~tA.pierrzsotj~tg the: . ~tudin.bfanli~ala ;~c~ad .Eoass~ss.the,~sensi~zin~;ac~vitji'of'~est suf>atsncea :von~persti;to=:studies-f.nvoNing the.~ssa:ot:gqlnqa 0gs::.,Tti~minirr+iu~i' n.umt~ar per grofup recomiiin.end~d by: tiiCVAM and t~re )~RA-0Pt?T5870::2800=W QECO #429 fe_ st :guidelines is Avemice. "" ~ .: . ` . . . 4..3: Husbatlti 4..3::'~:: Eau~ibraticron :.:Thetesf $f;itAals will.~ie coriditioried tb the hoi~sing : fa~if~Ies foi' :atJeastfive (5) days. prior to ~ttu~fy:Inon: . 4.3 :2: :. , usih. ..: Animalswfii ba~hoased7ndWiduaily in euapen.ded-.cagetsv~ihictt :coinfa~na tDltthe~ s~tc cec~iximeibalions in ttih`t3Uide tor"ft Ca(e.and usa::of.t.:etioratMAriatW4.:DHE;N (NtH): kasai'~M :v~rliita tiiEi~es .per w.aek: pTafp~e:rah~ierdnadtinrgo;o, pm:l~ac: rcee~sc+erbveecd~aeUiatdtuhsei~~aalgye.f;owrlmn~;e~.;::ic.shGaerF~rgiePdetaaTtuire~ss:ikivtnhtrroeleled- arr~ fs quipp~;W~h a 12~[ lighflderk ;cycte : Tehhpe:~":. a. tune ead tiurraid'~tywiit ha: cortf~~ait~ousty .reoot!ded :LStnp autome~ r~F~ ~!Tces.. 4-3.3- FQ~; Ftesti .pNRt (Diet #50i71) .win l~e.availabte at all On-49 ... . pnoww=M- . . ,. - TSCA SANITIZED AppetiFdix L MB :07.-'. 16,9~.1 .28 VUDY Tf~LE:: Local C.ythph :Nlode .Assay in :Mtce (L3.NA). AiIB RESEAi,iCH LASS PR;OYOCOI.'~LO: 6BS+ON1 pAtSE:Np. 3 af i1 4::3;,4;: 9tei;:~uili .bd'watlatil* .at.all times . 4;3.4:i:: ' . . ,. , . . .:..:.. ... .,.. : . . .. . : ` .Qom pec~oriried ,a~t0(irrriatel~:focar-(~E ;~imes P~ Y~ac;and,cesults,a~~ :~o.mpsred:;against.a list of sccepfa~ble levels-,of as':pnot~lded .by ft .w-ate t+estihg Eab.otatoc~ . . 4 ;, .4r. C. .a. . i. .t.r.-o..t. :. of Sfaa:. F'ro~.fkie..av~u7at~[a p~pl of~als,..haait9~y:famale :(must.ba:nuEl~~parous and non .. ~regn~t~ tttlce Of the sartt~:a~speciffed: hereihw~! be~ass ed ftr:,groupso ~s ;g,s~ndard. ac,apted methcds:of-ir;~ctdo.mfZetibn:; The. rnttroc~ for altaining ft random, numberawtll be. recofded in-the stiidyfl(e~.; 4.4;f: ~?r~study~t3odv ~: .At tite.irtittatton ofttie study;`the:w.eight varf8~tion of testanitrtai$-:wfll. not:exca3ed t 20 percent ofthe mean.body .rNetght.:,. 41: Identificbdort: 4:~:- Eacli' cp~e v~ip~:be Iderstified :by a, cage tag indk~g tlh .e:date of:dosing, best articte Id~nti~cabqnf. MB<~oject :number, :close aevct, number~and se~:c-of.aniimais . .:.... . . . 4;:v.2-". irnaf: EecN.:animaitiiilll:be) :Idiaintffied by an indelible:tail,mark conespnncfing fD the numbers ddiruin~e~edan tfie data:r~alfecti~n forcns; 6:Q.: Pii=R ENTAL.Clir3lGN :. 51 :I .. . ... ..... . . . . . i:'lie L.i,.t,VA dexernun6s tthe sehsitizstion potenNa1 .of aaest4ubatance by measuring C.~~t~.t,prrSoplttiCf.C`:.ye-frea:U~a.rn~~fafe.:rhai~moP: nh;ovc~~lt:ebse:~mn et,ahesuainreiacbulya:rd~e.tYemrpmhmrnnogdtte~se:rdlrnact~ r. ~:n. g.otrhaet:faasndoec::ot:freoxnpiqosdueorxey(uerairds)i,~e ARU~M9:a:~! ~+meter;::a.triettiod~slaown tq be eqoivatent tio ~7=thyinidinet~ased rrie_asur~i~N9nts af:IyrriPhocyt~ :protiferation : ,6:2- -Sumcnarv-6f E~ci~xiitienil( Desia~, _...... LtaN,~, ... PRQTPROW, ~~Y . . .... _ . ... DAY ~I: !AY :~ r._.... DAY 3 . ..; . . ~ Od.. ~' 4 DAY A .._..__ DAY 6 DAY 7+ 7+ DAYS ,O.,wT.,; e.,r. . . T -_~ - ,..:ETT -- , . -~ BtdU., ~P .. . . Sae~ae: = TCp:l. :.c.el ap.pHceUort :of test.subatance,, 3retbcle~orconbroi _ . BXdI~ . _: Amto. ;6:u-t.ia.r,ses, p:rp:e)*,.,"a.t:saai.qfriicfef:c(~e:;=..:erx6a.shtr.o~)n; syst~tnio administratiqn and processlng :ct:eadti :of :8ndU: in PF3.:(2O0.ji! mquse~l~ph node set per (on an,.lridiv~.ual errlnial bast$); proparatiori ofb sMglejcetlauspension of Lymph Node c~ns iuac3: = Bddj:y. 1. tVetght ;. .: = EarThk.Rrt~s m.ee,~aured,(d19.ltpl rnicrometer,OrPeacock.Diat thicknessgauge) within 24 hrs pce;~t.es. t., . on t3ay3::prior to4osing and pre-sacfflc$. on Day B, . P Post.l.n-life phase.:~ex-v. i,vo. :. flow.~y~kometry, procedums:perl.o. .r.medi m.. easuremeri.. t of BrdLJ-%~cctrpAratuan into.lyap~i -node cel15:(1MNCS a; nalyzed and Stimulatbri Index (so and:othe.r parameters calculateii . . .. .. l.TBS wetA~ro~td;.:P::a.. box I'm ptibns: .(2tb~ .b36 "41.7D. : Paqe :A4,6M: sptitiiefflown: PA_1OE8 1'e~c "(27F1'S361B'(~ s,runy TntE- Local TSCA SANITIZED Appeadix-L MR07-45961 .26 Wdo Assay: In )M (LLMA) 3,~- Ighoo.-jh1dw-figig"o AFO-Afte-AwAnk.when prop Will be. "190*1 foh'tho fWi*lr1 11, re, MRRESEMW-H LAU-1 Co PAGENO .L4 jai1 4.4*s0w*4 VOW& binsirllicdw*~6m -Wedublift ..df'the led 4:1, vlv ;AceboOAiue :vit~{, A~ ~00) Dimethyfsulfo~ddI :(DM3oI <' , , ~.`, , . 4:3:3 DMSO;P~ct~o~te:l~ilot .'('p''$AE 433) Ai~bane N,N-Daneth.yIformamide tUMF) Mile licefailricnsWt (I)MA) EmtoheMolt . ... .. . -$UWnone ," . jA E.4.301 Pm*me *001113(3) '0 Thwprefempd., . ofivi oil.. Wholly Oqu #pr;eparedbyyadd1h9-4 W1.0(qCWm.J0jr'wwy I W-W) avol 2A.P.'O.r. yphide Will -Ompe-M "Mom alsvfthetechr)*~a;*. . 5-31:' AM-P Pm. ....T" > notto be-msod(or, Ifi0dWWY s4vuld beus for UWA i.n ftdde D$-AE-4W(;i-QA-A >A -A001t. gx U,fof W n. of the SPONSOR REQUEST sect.ron bf th.0 54: egjg~M~ggat '1I:Th.4. .m0_ 00hi. k--b.M-.jj narnW'pl_l,d.p!." .fH.CA . .up.pIr6d :b' y.M8) .at-25%',or5G% :InAOO(Q.rWbWevehlde) .,Woll*:u6w- :eby SwrisorIn'sK ~_d.0-M0.0j0"t- oontobw sudh -p . . . y may.b-e: added : :, aweqto..--tno. .sxuay,' p. .1 ~004V. . W. ~ !. t"!"pq w..m .#%.tJLNA*ft-th6 . solv6nt&A orMA'g 433'. P#Y;kr.000yo ri~ . this nW bed:dded by M fh. 0 , _ . ._-. , . . . 5 5: N~aative.-Controi;_. There is'qosu0estad Q$tive oontkii :fijc fl~e. Ea.NA:; A;:r botifrol. s,ubs~nce"or q:matve, coritroi group .mary bg adde~ as an ~ddiNonal. ro:. i.u. p.~.~"t......~. .. 4" Sportsoc :arrd:at,additicnal-.8Apena~e(sees,~cwn 13::1 ;2), ;Alttesi:acad~ :grovps :be :c~pared co meu-respecavw.venpe:cvnau. group i788weeNz'road..y.;o: .tieX-i78 p1iD~e (21S)~b'38Al10- Papm.Rq- of 3,1 . . . . . . .. . . _ , _ -: splnnens~wm,Por:1886E : ta~:. t21s~ aaa:fal8: . p.46 TSCA SANITIZED Appendix L , MB.:07~~i .5961 .26 STUDY'1'CTLE: LO-cal L'Ytnplh .NQdia Assay in M116*4~:!LNA) NIB,RE,8EiqRCH.: LABB PRb~'OCl~L.:N0; .66~QAll . P~S3E NC1:-5 oi19 5.,6:. ~est Sofutton -iIre~'. .. :. 5 .6..1. ~~-...$,.::,.m..~s-:t.:..t-..~.-.e, .avOm.6ur~ng~solut~~.'pr~e~doia; . If~therest, : substance~ veh~~ndic~r~trota~ce .knovim, to.'pOseitit ~ iriiyats~i,ort ha~at~d, .all proc~du~ mua~f:be:,cartied :out_iri'~ :ffime ~iaod . 5.6:2: ~st A'rt~ P~a,rat~,.. Tla. e-sarrmP...;.Id~:Pc.e.~.??!. ~.iai:.i..v..k%.il: w:. e.:. d;a.,.c, u..r..r..t..:,.e,::n:,~f::d~;t;:n..t. :h:e~. .~x.w :.:.f~: ta::. .F. re. sh . . , .... . .piow sobir. dy. .oa . . . . Ii~io . ..: .. . .nsls~s.. . ..~... .1~$:~-.b~::P~~d,cin:ealc,h.,b~cfet~tday Su,bstances.or . -;., . .~. . . Fn..e< c::t.il,3i. .t-~".~c~:i. la. ~: g.:it:~. to.r:;,. o.rusi~g :a:r~gn.efip sk'urer. tieat ~ o~i. .e.:_3BC:yyia not.be~iiseif;imles~~e>~substanceas,krscrmtrit4tria:aieat,stebte. .:6::3: 'f'c3st Articie Conceatratia tii~aeat artwde ,is:.norn~~ji-a~saYed at~i~e ts~. tive; carisecuti.ve coaoentrart3ons from 'wthiri :fhe foii01viing One' . 'f0094`. 5(i"/o;.25r_6, 'ipJ. 610.:2..596;:'l,.09j.. .5I. d 250A, efia:: (wl,`v:fo~solids .:.vXy .fbr liqud1 s). T~e:Sponsorvritl,~dpr.~te _, . ooncentrakions~to iie:'useda~n .. ... . POWd~ -i3' :~l":~ltiased,-U,.p.on....previous expe~iencje orstadies i;af avait~bke), ~truc.Wro~activv,itY-analysis~ d+erme1:0 .ta~on -and s. olubility Opt~nal..test:c~q~certtrations will bs. Rc+eparsd Wood .~porfahp ~a~:drnum sol~f~llt3rofahe'Oest aervte~nlteolfon.3;oh-es.uveohhlcsiuop,pwohr'itl:ed:. aitrQd.iaiQtugaonve~ctEtovreseIrvteiEraettsony,s.tTe~mt,iej: seeo 5:1r -; .~1yo:mca~yl,.bim~'st~ertreteoqRqu.u,ivriend.ithne p aae ;.s:.a: f o..r:in :additioota.anlrrtiatfon :P,cesca~een.(se+a643 .)~ . o:..d.etermrtte irrita' and tht eshoida., ,tiolab~)f 5:6:3,'f: 3nitalfai Preecx_een:...~n;irsi~al ,r.mE,s~. iQ. r~,,i~st .{iearswelitng; eden'aa}wjli be-:petiormed r~sin9 ~100a~~;51~i`:arM ;2~R~6:.ot`:testart~'(.o.r;t(~e;;3.: ;tiighesf;!concenf~t~ocrs, . obts~rraQ(e 1n r.osen ~etiicttd~.. . :8ix::mice:.(1w~:per concentrabon);wili t~er~sec>~arud.tkie,pi~escreen .w~t be: icor,tcducted itnd~r:klet~It~tl:c.oiicfitlor~s .~s;EhQ maInaWQy, except3~?rthe.assessmeni of ~ymptt.I~ilQ::prolifedrathte::~ivity: ~f ncr ~a4o~~ obsetved::~~i' sweNtng Kz5%), then *m!Wno=nI fts,iI 1.~s .wf-tf..be u. 6edJ.m .the.- .=ln stucl~,, l.f.sionftant 1wrosso !Pj: UmU L -k -A should be Wormedi 5:.6;32? 4. ohoutd,be, riomw.o. uOng waftIit 0.0 12-:400, 1 .0s. M.WMi0j.*0-,e-see:socW-14~-..1wn. Wba#qns Ot,n,*3.mR;q. or .6 perfo;;W0 I loalv"boid mgtn nor!4-rdtab IS dOt".1 .57, . . G I must be wom .c1mrino-1his oPerstOom 61,T., r A&Jjgatbn~ .Sa.ch..gro ofMicarvAll be-treat6d :by topicsif .Spp.l.it.aboO~Of.a.,differe;nt.~WGCW qa-lim0.pevdsy f6.rA. hree wVd~see-..m-&(e2,,5d0ays :.eaCfo)nVtIrloll.b0ma6dmwlilhlbWwisimrde.:.&usWJhwgi:tqm:poas.M-vveeh:.WdA#sep.O*.fl.aoojn&w,,eM-cAgPepltlsumonvAll be spnaaii .ove~ t6e=entire:dorsala.ucfac~ :of .tiie ear' 'T'Iie tim~ ofdosing wtiU.:be recorded.. i78B :v,rotkz-roed;'p. :a : bon :l78 . pitonn: (2146SB"4i1A Page. .4S~4. 44 ' spt,emenstnwn, .pa 1 .80E$ f5iL_ (2119638-te18 p. 47 TSCA SANITIZED App~att~dix L~ li!!8 STUDY ME-: Local Lymph Na*.:Assay In M100 WA)I MWRESEARGH LASS PROTOCOL N0:45SOM , PAGE NO, 6 61411 5:.8 : 9~~.~n~ 1RO;gr~ratior, of ~sdEJ, in yivo: flve dvawte~ ~he BrsE fiopka~ ap~tic~fion of . test.ar.~de; att.r1tc~ei~4iil;he.inj'ected;1nbaperitoreatiy.wifft 200 ~ii of '* ~Bi~~2'n;deoxy-Urldihe soTu~q,In {1~Br~i,t1, ~5:miglmfr;irti: PB$) ;. _. 5:;9: Obwl*awis: AN Wobserved or~ il*gi~ftir s :bfio'beT iftitatibn:at ttis 6. :9-2; 5,9 4: . _. . . . ... : ~~am.fi~taiuan;, ~iae wll, be obt3en~eci~drics daiijt ~fot":~~ii~ :~it7ic;at sigris; eitber of loE,a, .1 inl0on .,att~a~a. ppiic~on si6a orof .syaEerli~ .... ::: AIi;oE~s+srvaktohe:i~il! bi~ : sysp~rrtatlcaily ler:brded;:lwith rQiAicds ttlai6atned'fbr,eacil iriili+tidtf'sll :"trilEwse. , ,wtlt be fecoi+d+ed pre~taist ~i~;ii.pricrto. $rilU irije~tinr: Signifu~int weigh; icss . (2 g or ma+a~`wiii :be noted arid add . .. . ItYl~iSltcikvneeHsisn:~mai:~at~~uo+the,n:zea;ieinr3ss'oCfveNla:c6)et~ atraik.eimnao!rHiii,9D..abye1b(st~:~~+-,:edd~'sf~o3r..eDdaey:i3'~:(:aartlatpipJorroxeirlytfilatteemla.y. ,.,.da8hhdo.u~erasr: afbei:~ie; ~do:ge~;;and oa 0ey:`8 . :y~nig:a 1;fiiGkliess.2anige; digit~i niicrortiebeir or peacock. D141 ftkn.ess Oi!K 5,10. I.' 5~.~i~; ~Yd)lPS~ N:o, isf".e..~ , . g " , 6.1.~:2: ituma,tteljraaevil~aed~us~ig :COx.: inj~tion :of BnQU; ti~a a.ui ~ ~ ~?~l~n.an~d. ~. +[. ,t~.. . . ~:: . o.f~..+. V. . m..oh.._.N.o.da. ~.Cel~s; .F ali. -niitie-dr~ii . ' auricula~tympfi hcdesfrolsteash:ittouse,wltl be;e?ic~sed ai~d :aonmbined, `On:an;:iiiiijv&iaat . animal,besis.,singie celisuspensic~son. . - . . ~. od+~ ce:11s. j:C:NC}.wNI:De<.prepeii:ed::~oiri the.: ~viie~ted;lymph .p.od.es:>;y genfle disaggregatt.on, artd e,r,ydiriocytes tivili be`Jysed~ariid:rerrsoved. ft~the`L~tC "Pension 5.11 : Q,ptronal~ttnrnunochanotupina~i~Ttaafmenl =; An-iiquptt~ftil8 :calis :wPll .b_estqtaed:at- :4Car~SsUtIo'r-fa~~.Caer.-tmt'eSial~iiitaeTf-:oerX~pufp+Bb8oS~.1.7oZn;n8o::aftf:,a4ftiborB~o'p2tQi,*on; alX:ofCiDo3w+-..,c. . .9y~ ~net~ ~r-a..;r..1k.1ld.Iy.Q.sf~'~'. .SQ~~f,.'f~ik.m.?.m...uC.n8..1o.!p;$.h,. . .e. . .8.n..8a. ~EyfPeM.oB~: SOP Vol Vll.fl: T,. 51~: Fi n ~. of`Celta; At1 al~tmtot:~te;l,tVC.~'il.bs~c~es~f~rpd :an!Jt1tt alsr~ta~ie:butfe.tor aicohai and, Mil be>storEd at;-A'$ to "~3aO uritli fnrthar prooes5ed:. StOraqe :st+qw :ndtex;ceed:immortttts., 5.13: Oelarminafton ,of CA Proiiferation:: . 3: .13.1: . .. : . ..,. . ,F,,~~ ofC~* :A~te~ propidfum i:odid~ .aiin~ng,:asirgis-celFaugpensfon=ot 1.N~:will kbe an~iyzsd:u~;.~ ;8e:irfot~=Didc~tson #low .CyE4i~teilet~ spec~fir,aiiy.~r!ograminqd:focprao~sdium: io~de staintng ta enuri~erece ~ud~ate~ c: e~s ;in ihe~i,~t~ph;no.dec~ sys~ns.lat . Ti~e;tofal . nufnber .of oe11sper caicx~iated irom1che;y~Itrea Qbtat~d :b~rrpui>YplYtr~ _~Yahe aRProPriace.:ctpwjon.:faclpm , -: . .. : .. S?$liYVenlza'oa~'E1.o.'t~oX~ .T8 c iiho!s: MbYlf86+4rtt0 ,47,b!,.,52. . sptn neralbwni i~s. i$868: v; iii {rtF1oo?18t0 TSCA SANITIZED Appendix :L MB. b7=15981. ..28 STllD.Y T11'LE I:oes1:Lymph:Node Assay kn Mloe (LLNA) ;M$RE8E1kOPH LA" PROTOQ%' .N.0::5.650IV1 6:14: Otaterrxitnetl6n of BrdU. tncorooration: . , .. . .. 5:14.11:~~, Of QNEt,ofCN~."'I ..beadd :denatured,so;thac'aheStdU :antfEbcdy ,can ia~cess:.and :quantttati'v:etV:Iititradtvvlth,1hm:.Brctti. ttiaE:has _besn incxjrpordtetl .lnbo"Nie! c0l1qTst .. 5::.14 :2.- :N~_r!~~q.ry~:~~:.f~ettular:MAtertai: .$emPtes:_wip tfe :~.eutratfzed b~'washing ti~a..a~lis;:wifh bcuate buffer tpH.8 5~; ortlthec +~om(~ara~le;:neutra l.habon buffer. . 43:. Brd~~ssaecifEcStaWdna-nf'Eeits: NucW .wia.,b.e~wash$tf::with es~inq b~rffer.arKti.n~ubatest ~uitti B~d.U~. :f.li~oresasn.t eii~body;.oanju~te .: `V'he n.uc{e~ w111. E...~s'.?..~. .. as_~+e~ :.~oio:with stbtnin-:bufftr :an4d, :res~,rended'inP8.5's~oeitatnGig RNase:A:arid;~tieDNAv-s1?:. .ft..:.dy.e . :. . ProP1ctiumao.diclq.-.: Followlnga.t lOst.a:3.Q~nu.t~t:lncubatfon.at.tnorrt:temperatura; tti.e. t. ~. .t. DNA content of1he;r.iud~, ;:a~a :wal(:as the perca~tage' oFn~icte't~eht~g.posilixe:iqc,Bad.U (i e.. perceritage :of pcot~erattn9.ty!r~Plaocytesj :wltl f~e:~mlned-u~tng flovu:cy6ornetry 5..15i ~Du : The test duration of tktiestiuly ts ai1east eleven al1)~: d.ays: ... 6.1: :Fiow CYarriete:: . Flow t3ytornetry and~l.la~ioell. proc.ewss'rn~..vvt11 be :condu~ted a~oidir~ to MB Researct~ :L~faoratorles Sf;ar~ard.iDperaiPrg :'PrOceddires : t.ympNAode,,oetlanalyses vdtl be: performed using- a B~eotott4Dia#insen FACBcan flow c~ytometer ~asirr'g 15 m1N af~p'ov~er at 488 nm eitcifat#orc;~aravelengtt~ .:. i3Q:CeiIQi~stver 3;3 aoqqi, . ~ ... ;so'' ;on at~(adnfos~.E3:4 acquisftion i~ Vr711 :liee. used tQ cepf~ ands'~re dato.tList Mode Data, f~es; as::,t..NQ:or. .FCS) an a dediieaited seaus>rnet~!otti'dtiy~,:. t7ata:l~s:wltt !~s sir~aSyzecf :c~sing, flowjo for PC crCeitQuest to determine appnotxiate anatys:is gate .anii:'lo posi~ve;~LNC`:poputations: T,O: 7. .1:: ANAL"tSANt? ._qA C . _ TTC~t~ QF=Ti,AA "iN1J_~_"~iN~RR1. fNDEX~~'Si1; .. , ., ;Da1~ A~tVSisi: .t=onanalysls ef.irttt~vtdual;animal .tymp?i~node sets~(~ht.and ;ieft slde:.dreinlng local in'sides);~the.:prolifetare .cespanae:Qf~yniph :nodwcells: (INC) Yrii) t~ i~cpressect asahe.tatal aun,biar :df BfdU-positlu'e 1yrnphocytetper;(indivldua4 .anfnmaly:yrmpti inn.d. . e`:sef&.. Mwrnesn-value of' ffxe fatal num~r(~#:BtdU-~:bsiti~' cehs .and:ft~ ass~iat~ s#andafd .devialion :(S:D :) vvli! t~e catc~teted :for e~e~i-g;roup:. 'Tt~ SlK i:e:,ttia:i~attai~of tthe ~:BidUatcoi~ratkiif'tnto .LNG~S each 'fesf ar~ote:,gtaci~r divlded:.~by'fk~aE :ofthis:.Vefiiae ;group;.:wtif ba`:caloulatsid~foi:aacti test group: accordino_Eh Equation 1 Eielovu:: :EquBtfan 1 : :. 1. .V...t..e...a...i.. n....*...B...r...d.._.U...+.....c. e. . lts 1n TfWaont Group luean: ..#Bidtl .+ .cetls: in 1i!'eNicle-C,i~iup ?:2: :EgitirtoCa1 :Resteit~ti: ln .`tti care .wt~ore:dcse~refabed increaces tn ceil:pi!olifsr;atidiiai:e:;,BndU : posti~ie~calls a~MIt ~it .a SL-thaY ~~proaches: ~ut ~foes not rie~acn 3; the i~gulatory gutdeUnes May require. thafiaddfttonat+fiesds tte ~ecfomled tisfi~ hgh~erc~nc~rit~atioiis-of,.ttie. testsubstance (or in afi;other ~likle) if p~le:. irt sucl7 cases; the~+effectof the vehidia:on thd oi~bcoiime~shautii alto ti6=exaem . 1765 wbalz icait, .ti.a, tiok ITS pjlone: (t1~~:03(H4~10 'Page ~3,Of~ 3p~iiae~stow~pg1800 ~a7c::(~8):396-t~Sfd . TSCA SANITIZED Appondix L W0. ~s~.t:2s STODY TfTLE: Local.txmph :Node Mew l.rt Nlke (. 1-LM) .._, ._._ . . . .. . .. . ... . .. .. . . . . . . . .. MS-RESEARCH LABS AR4Yt~GOC.:l~10: ~~~OM _ . . PAE3):'Ki~sB af ~l! 7 3: ~tis~l AnalWSis: Foc ea~h test group; t~ae.lndividu~I .31:yai_u~abrtgayr~: rnean Sl and standard .dgviatiitn wUl :be. catcu.lsted, if:ftsrthar,stafimticai,.snalysis a~ rsq.u' ,.. ~: . .ansilysis :wilThe. , .pedaarmed.;only'ilpoll requesf by,thea,ponsor : : , 8 .0:. DATA jW=kdk,0 'N-. _, . .. . 81 : Inferoretebton : A:subst~;wibbs.~~g~rdad:~saserisitt~r~i~#tXeaCNA'i~ :a~lee~t :Qns : , eota,Gentratiotl aftt?e~`art~cte~~esu.hs in a 3-fa~.d.Q~:g~Iter:incr~~-M: ~::N.~;ptctiterafion reladv .:Ntat:.cfCaritroi (1lafiiele) ~ymP~:nod~s.as :iri,dk;otdld byran :Si-4::0. Tha:datruaftoulid slsn::* , com,pafi'tiiewtth ;a.biotc~icsl:dose,aes~pons:e, eiiqiough~n ;~tb~r,e~,pei:must;:b~x.r~ade~ ::a e~aily at: fiigh topioat aFPtiaation.c.4noA~thsb.or~s., :foT.b!cal :lcritatiotC~ . immunotoglcel.: 9A: 9,1: 9.2 pf~OGES~: _.. . ; .. ,- . .. Tiss~: :0000t-th.an ti*aymph nod.es processed as:abo+yei .no othertissaes wlll be taken . . . , .: . . Or~tkin~l'Tisstres:. At #te ,bpdon.cf.:Ehe Spgnsor,.fhe; d .. , ge.sibe:{~ars),w~1'be;eo,rcis~ed :anr! pr.eservedan 1a~G.,neutral- .a~fn,forN8~~staining.an~~fo~kat~evalua~o[~ atart ad~Jor~l;aost .. .Othertissues;rn:org~ns ~ay .be, ape,ci~e~l: ~yahe-Sp~or~so~ fo.be :~sqtateid and preserved' HistapaEt~oiogy~.wiU .be.peifonme~~by..W.kay 0irown,.D:~I:M., Ptfa~_,1~A~!Y . . ftesearr:~..Pati~ofagy Setvicesi. ina, Now-8r", PA. , ; .. . . . _.. . . . , , _ , 10.0: i~Ij;~IEON~OA TH~ P~30--'IroCaL:.:: iinY otner~drtt to_ardeviation,from t~is;pfofoool :~iU :be tuily dccurrertte~, ttnheatudy tCe,_Indudi~g .the~ reas,on-for the ~harw.lho atifficrity`tarsaid dhanqe.an'd th date: t[iefeof, .-, , . . , - 14..0: REDDRDSTO BE IYIAi_ A1NE0 : . 11 ..1 : Coilection of Dab, :Altdata geiierated:,durhig,the.c9rnduqt :,the sfudy, ,~p be ~rdedan .ank on worksh. eets, . All entries Will E~e d.ated, initialed and verifier.i.. by.anott~er pe,rson,,: i=lau.vv.cyk9rr~~y data ~ies WIN be vKit~protected,. 6aclced-up an a copyatoced :oif~sife. 'i'h,erqrigirtal:computeracxtuirea::dafa~,nrfli _be anaiyaed and :hlsoogFams, dot;ptots ~aF,a.%:p.a: i"st~e i..NC will be printed. out fg~.eac.th :asimal a~id saifpoi~t; ani3 ineliidd 'if"#t~e ~cv data.. . . 112: 11 .2 :1 : Oreit ReoocC A dca,lt-:n3pofiwill to submitted-to tttie9po~ prlorto sut~slon .oft~ ai report 1765 weft ro" :p.0 . box 178 pfions: fZtajs~~ssio: Paps:,t4. of SZ , spl~lne!*towi~.;pt1.8988 rax.:~st~tais TSCA SANITIZED Appendix L. MB`0.716961,26 STUDY'.Tit"TLE: .itocal .Lymph Mode Asiaa' y. tn:Nltca ~4LlVA). .Ma!"EWH Lass PR No, SeSQNi i~~~E'~~ 9 of 41 11 :.2,2: _Sna1 iteoor~C Poilaviiiiig apprnval .b~r'ii~eaponsor o(ti~e d~altxepor~; the-;fi~si reportw~ll:b~. submitted:and will.i'rtictticte; bUt not be Ifmfted to:. :; Spec, ies s, fratn, sex, nuimber.,.e9e and source,of:it :ankno(s,:. .- i:guitibration, housing. conditi,ons .during exposure -and post.exposcrre; bedding materTai ; roolrr tamperature arid humidity, f'tght%dark .cyrckk :diet~andwater Method--of-random -asilgn%ept ~. hysicai:nature, pu~ify, .stsbiq.ty,:~reti..iat number of test:articte_ JusIffr.catio~i- fqr:dio.ic...e. .:.a. f. .s..o. h..r.e.nrlveFticle: indiviiiy~f and:test group;data i;t.e , mean and stct .dev:y present6d in tat~ulaa~ form each .onnup : pesc~ip~on ofi :ailvqrse 6ffe~cts:.of;teatment csri~thiQ m(ce : ansl:co~'..ipit~9 eval~ting ;f~uf_ts_. . ... . . . . . r i~e:,iNUmti~er of f~mpt~!es: th~:96.~~dta+ oeUs,and`t~t.e #. .B~t)+ :celfs f,or e. .. ..~h. a.:r.i: .ir: t. isil li :, cak::u. ta. i.~.cT .~limuCati~iail.dexfoi~,ea.d. i;9'~. ..?.. P. .` ~i. ~mP.a. .t..e.. ~. ::to its m.spec ive VehicCe .1Yontf..0i~grouP~`:wrA beprEserit!ed i~`ta3vul~fnrm 91.,3: Retentia.n~: 1131: -Raw Data:. The .original.raw,data wilt be Wat US Research by~project number, 14::a,t. Final ftaoat. Ttte originol fiha( repoitwill ;be. submitted to:the-sponsor a. nd-atrue:and certJfled copy,of fihe orlglhal report will be tiled at NIB Res.earch by sponsor name :a,ndMB.pr~ject n4r:mber. 1 1:A 3:. T'est:Aticlec. Any. .rerm~infng tesi ar#idle will be reiumed to ;he spo~rsoi wpon ..subrnissFon ofi the . ,stuay :report, . . 1 ~t:.3..4,: T.'issuesr geq. s. . ~biocks & oldes:wail, be stitiored, at.MB, Research; aii.d inde~iced by spptAw .name and:MB_:p!~Jeat.nurr~.t,aer: The;sporso.rwilf :b.e;:coe~tacted'te :~eferiit(r~e.t~at:disposifidn .ypon. submisspon,of tl)je.report.. , ._ : . :. .. . . 92A., GOG?Da.ABDRA`CQRY' g9kCTit!ES i2 ll :: "ftits.study :will be..cond~rcted i,n;,~r~ordance widb,the Ciood,'habor,alory Pieicttces .ofthe EPA, 40 :CI=R,1~0 a~ 79~, FQA21 -CFR b8, and:as :speciffed the Prlrldptss :~ab ~oOCj L,aborator~c Praaice, published by tthe Cir+gar~zation for Economlc Co.copera~ofi & Develbpri~ent. (OECD), 1997 . . . . .. . .MB Rssea.rch Wn'tLhave.on..Rie:a: c;Qpy :of,this..Wntpd. si9ned;and..da#ed by: both. the respolis~le..MB. .Sf~ly Dt+nectar;~nd i:he.Sponsor's authori~ed. ~presentaffrte. 12.3: :Q.rra. litu!;q~SUCancer 7he...Qu81it~(~?!'ar~Ce tJnit +vil!ar~s. peCt at_le~st,p~e :aitioal phase ofafiis sttidji;.~audit:the. w data:~nd .~aud'r.t`the. reportln .as~rdar~ce wifA tlie Sfiattdard Cipersi~ng Pi?pi~~ures ot1~8:and ttirrappiicable:gouernm+ant:regulations, fi786'Yfl4'ri~2"n~ldia?_dbOX,i78:. pfionn ::(2!8):63a41.~9 PW 60.ot32. $0n061tt0wms Pa. ISO." ~i: t2fsj sa~~s~s . a , p. 51 TSCA SANITIZED Appendix -L. MS 0745961 :26 S'fUDY rtTL,-E:-_ l-iocai,[ :~ir~ph Node l~my7~ Mfcs (Lt:f~iA} or,att:F:teporr :>~~. Y. : .. w: : . . ;: o.icio . . . Rb.. p.,o. . .r: . .t_s.. ~. . .nd. .:~..n'..v.o_i_ic.a. ..s~io,be ~ai~taa : Idl~tt~idaa4tik;i+et ~13.0 $P+~NSCrR"~CuE4r: A3'1'. ~1fi~l:$poi '~,rtii~ssCo:~h~ ;lhk ;Qrolqrol.a . . :.. .~-. ,. ,. .. . . .. ~her 1~shick:(s,~s :seetons ,3:5 & 5:3 2F`..,: .'. .` , ~ MB RE8EAMH UlBB : .-. ... : PROTOCOL AO: MOM , PAGE N0 's40 ot-.1:.t,..-.. . . . -- . . ... ._ . . .:__. .:_ .. . Add::.t..~. :o.t. taLrll~h~ele ~. s.. ee.,s.e; id, ~. O.ne..3.:~a~8"5-3,~. 2)::, :. .. . .-. . . . . . . . . .. :., :.:~.. .... . . . . ;.,~_ ._. ... -... ..._. .. ....._. .._. .. ...__r...,. -..:. ', tllt(ona ... . ~ " . . . :.. d~,f!Yo.SLS . CN1;50 O'~iaiv4 Q;0 , .; Q C)ptiaiiladdBoiisaE T'r"ssiiesl_te,qrr 044.40.94 _.._.~..-.:. : - 13~2 :" Nhq.nJQOr;"D~';dWattod to a ragulstoay aqeney? d Wd " 1Kx,~- t;. '.~ t~:3: ~~,3tudv`tde~tNic~eint.F. ~rn.l.,l .b~i,!1,df~~.8te.~ .iri .thBrE.~landsu. ~.o` .r. t.,n. .t. ~n.ooEanen, +: a.. H.4a. ; +. .~s~:.:~~ - . + ..^. 13,d: : reae~k,ficle~..vyHJ. b.efd~tfAed ip~ :tttte.r*Ao.rt 8.c~d a~rpporl:t. c. ~g. .cloaxM~te. b. .on,exeqf,i! *s. U~di, ct;**lowr . t3<. d1 : -_ . . ~ . . : ~'+~~aesta~a,c;teF~s,~den.t.-lt~edssf~lbws:"~'~~~i!~Ri: bb9~s . . . .. . . . _ : . ., :W~.tk!?ie+):aPgNCSble) . .6~ ;- :~. .kotl8etch#.. _ - _ _ . _-,GAS~ 1342' ~ . .F.e. s.r..::. ..~..~..b. '. et. i. :o_..ii:~. . {... .l~.'~.'~ 9Av04 . . K~~.- . ' ._~4. :_._....I . -- ...1~ ~4dd'dforiar~coiios` ;,.,,_ .,`...._ 13,,4 '3" 4~R ~t,ovia:a~dude:idenqEX : p: r . ._ .l pWd ~i:s~n P~ dnin:c<l~ud~'Y~-dtandurf+i'~iif.qpn!nPHo!yt: .`: -f.f(iipsA_~t4tb~:etCsFcRr~wts,t60b;R~a0e4vi:saew>e~!db7j0i?lh~eQ:t8;tFudDyACi2r1e~tot CF8 .58~7D5 ;;OF:;U.~2~:: .Y~Iqs uk>bnnagon ia: . QK'o~ovlded :~~~~i~~ ;or;_ ~ Cl:; noi: avaUa~ile ~ .. a~ a. :.r_s~ ; - QS?T1~. . J_ ;.l. . ., .~., . .r: ,~na. ERA-- Jdza^d~s ~ ; Y,'iJo`: o Ya_s. : OV_ ._~. . .~.._ . ... . . . .. . ,:. . .., :. . . Cpx!liCale.`EPA: :' . , t!,Number) -..~.: .___-.__ t9 a ~: :li4~ea ~astd.~, re~ ~+ .._'" (~cr.Gat. y..,'wme. sad~ n. es. st :. arl ut~ ~;~::/oo:av . ; :... - . .,o..rr- t- Cre . i~"sGru~tiorn ::(iEall :ariader'.tc:Suitfy-iriiWon iMoar~aldon-toi"costs) .~ u. . PS ~:a~o+, .e~i. . :t ternpara.~une.~no:ct.t,argal . . .'~a" .. L1 :0cpres~ :car~t.ec :~Amb~rittempe~stiue : . . . p. :.C~~!!~??t :~cI fee- A*$ ciecessary: . : : . Thkstudy:is .ay_bs<enc.~ur"~ts'rad ffirogh c>i~r of .the test;v0.irtpouW. . TOetiest.ofaiy;knpeAeit~eand ;iilpr;in:attpn;1N~~1est uiit :an unrracessa~idiplo tion :-of- ~nY:P~vicfus..~udfe~ . . 13 .5, V ::C~+~6dq. .~,p,sti,tv_: ~fiudy .i~aaWts:and ne~orf3.wi~,tis i~leasbil : to WOW t~dWduats'iiienCfied in . ~5oidsor's . .l~:a d~vu+-~o; . z,~oa. slgnsd by ;.~nm.es P . , . .. { : M. sr~r . s. .a.ae.sAtC roaa~low IBY: .~ FOR . W " . . . .8~ ReoulsE ~a' ~~,o .w .~:~~uZb~r..-/. :., ., : . .: 1Aa$T ~ . . ~ia.'-~M. 't. `'- ~- :' {~yR.ywplinYc+arris) : ~.~.... - tlMWdM~~dforef~. ~iiac~ . r~ror~~~ 'I r~sd wvoi+(z.ioaa.-pa. wuc ~7,.a -- - . , pho'wq:{3Ybt $3b;t 10 - . . . .. . < "-.~__ : ..... .... _ ~ ~-4ahooo' _ ?)' sZk+t. -., sfilntarY~iwin : Oilnet fdk:'tR16t5i6~1a16 P*. $4 of B2 TSCA SANITIZED map04n. dix . 15861 :~28 S'Y1i0Y TtFM l.oo.al:Lyrnph..Nodo. qs:,ay.ln. Mtco :(LL,NA) : MS.'RF_SEARCHlABS PROTOC~iL,;~lO: ;5B5tiM ., . , _ 14..0 :~"t.RE~~AR~Ft A+EKN4~,~: Request.for fM.Pls'metitsitliu,ti cf this p110tocod'snd receipt o~'ttt~;te~t .attic~e Is as;knowl8slgeQ:by M13ROearoh . 14 1 :rgolArtfide,.ide 140-1- Llioa-R~e(Y~=: .~~: . ,, . . . . . . :. .~~.... 14 ::1 .3: :14.i .3;1: . O:',Nat$uppli4d :bySP~nsor~ nr _ ' ,. . 14.'1 .,~:2; . : .~; ;Rec~i;Y~:~!~ . ~,riaweii,.b-y Sfu.dy Direcfor:. . ,. . ,. . . '~~ t . . :.. , Ttle Lac6rtw~USdA .anfmelsuPt?rkor~...... 74.4: : P60~ S1. udvt)e. te.ai: .. . r. _ . . 14~42:. Fw?S. Q. . .~.. i-nenCA1 .T~. 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St. ooo. r0il..lwFiaesi:iaatleg":i.it. .nl.a.di. il~c~...tr.ee. :dv. ..i.ba. e. .wl.4b.Sd-n. :t~:.f~Uif.ts. d=.l'rftoslfmlalUtiotyonfe~iRl~Jt'~adknlitalh;Gae_crceeD;raiiaibld~,il;J~,Bleav!i~idrarfudisti:;ttpbfe;'.a(icR~GltJwCvJ!:ccfe`.:~NeiBand: R.es. ea_r: c.:h. huii'iene.c~efre: '1'Ii.Iq ;1.A~l.C:m~i;?n~u!it!b!s?~:eea_n+~Ni,mIcll,r~gitdr~eedwl.ntllt~hseYp~rsoetomo}o.l~.aorii'n~uaal:^raeii~ppotirexla: o.'t~ bo:'.~+tsthPltus.droeitvdiie:owif. wiicl.'tse.1E.ie dorumer~d;:Ua-the .tJa~l9G t:. . ._. . _...~.~r . 1y6:Stis+sMi ..:r. o.ad. . .. D. . ... o~. . 6ox.aT8: . . . ptrpnr .(21S):536A.i10 ... . . . . . . . ._ ... . , __._.._. . .. . . .. : _.... . :, .. ...- ..,_.:.~.__ .. . . . . aplnnersCown. Pa 19988 tele (Z15).S3f-dfit8 Pane'62 af'0