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# OAR Box 1846

Prepped by Ollie Stewart



### Document

Number: 

# 66 ) ll-J- 9

Docket Number: 

# A-90-0 7

Printed 11/18/20087:30:16

AM Sheet 66 of 93P. 2

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XBSTMf l FACILIT Y
Toxicologica l Sclenet a Laborator y Htalt han

dEnvironmen t Laboratorie a Baatma nKoda k Conpany 110 0 Bldtevay

Avenu e Koda k Par k (Bids . 920 ) locateter , IT 14631-361 5

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BITO T sronsQ i
Ketone o Pane l Chemica l Menufecturer a Aaaoclatio a 250 1 M Street , B V Vaahlnfton, D C 2002 7

Decembe r 7 , 199 0P. 3

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HARL-MT621S T Pag e 2 o f 1 1

STUP V TITL E Meaity l Oxide i Combine dRepea t Doe e an d Reproductive/Developmenta l Toxicit y Screenin s Tes t i n th e Ra t

____ Th e purpos e o f th e screenin g tes t l a 1 ) t o determin e th e toxi c effect a o f meelty l oxid e i n mal e an d femal e rata , and 2 ) t o detarmln e th e potentia l fo r meaity l oxid e t o affec t mal e an d femal e reproductiv e performanc e followin g repeate dexpoeurc a b y inhalation . 

## Tgsxin s TMlhin

_s__i Toxicologica l Sclence a Laborator y

Healt han

d Environmen t Laboratoria a (BAIL ) Eastma nKoda k Compan

y 110 0 Rldgeva y

Avenu e Koda k Par k (Bldg . 320 ) Rochaster , I T 14652-361 5

Ketone s Pane l Chemica l Manufacturer s Aeeociatlon 250 1 M Street , M

W Washington , D C 2003 7 Sponsor' s Repreeentatlve t Barbar e 0 . Franel a


### BTUP I PATE S Initiatio nDat a

Experimen t Star t Dat a Treatmen t Perio d Experimen t Completio nDat e Propose dRepor t Completio nDat a T o B e Adde d T o B e Adde d T o B e Adde d T o B e Adde d T o B e Adde d

BfiCULATOB

YCOMPLIAMC K 

### Tes t Standard ! Thi a etudy

vil l b e conducte daccordin g t o th e propoee dOBC D Guidelin e fo r a Combine dRepea t Doe e and Reproductive/Developmenta l Toxicit y Screenin g Study .P. 4

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HABL-+H6213 T Pag e 3 o f 1 1

Thi a etud

y vil l b e conducte daccordin g t o Goo dLaborator y Practic e fo r Nonclinica l Laborator y Studie e a e promulgate db y th e U . 8 . Environmenta l Protectio nAgenc y

Goo dLaborator y

Practic e Standar d4 0 CF RPar t 79 2 and Anne x 2 o f the OEC D Guidellne a fo r Teetln g o f Chemical a (C(81)3 0 (Final) ) a a require db

y Counci l Directiv e 87/18/BB C o f Decembe r IS , 1986 . Inapectlon a vil l b e performe db

y Qualit y Aeeuranc e Unit e o f Baatma nKoda k Compan y t o determin e complianc e o f al l phaae a o f th e etud y wit hgoo dlaboratory

practice .

TES T ARTICL E CHARACTERIEATIO H

Genera l Descriptio n

Chemica l lame t CA S lumber t HAELlo. l KA N lo . 8RI D Ko. t Experimen t lo. t Physica l Deecription t Sourc e
IBBXUA I Vepo r Pressur e (m

m Rg ) Flas hPoin t (*

C close d cup ) Boilin g Poin t < # C ) Specifi c Gravit y

(20/20*C ) Molecula r Weigh t Meaity l Oxld s 141-79- 7 T o B s Adds d T o B s Adde d T o B a Adde d T o B e Adde d elas r liqui d T o B t Adde d



### 9. 5 

# n 129. 0 O.S5 7 98. 2 [MO ]

Taa t Artlcl a Purit y Purit y analysi s o f th e sampl e vil l b e conducte dprio r t o th e star t o f th e study . Th e purit y

o f tha tss t sampl e vil l b s specifie dI nth a Tastin g Consen t Order . Th e tes t saapl e vil l als o b a snslyta dfo r purit y a t th a completio no f th e etudy . fltorate Condition * Th e tee t eampl e vil l b e kep t i na chemica l atoreg e area . vil l b e maintaine di n th e BAI L Archive . Bafat v Precaution * A reaerv e eampl e

Preceutlon a vil l b e take nt o avoi dcontac t betvee a th e tea t articl e an d clothing , akin , an

d eyes . Routin e lndustrls l hygien e practice s vil l b a employe dl nhandlin g o f th e tea t article .——l* U • I i W I *

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HA2L-MT6215 T Pag e 4 o f 1 1

lEf T SYSTEM Anlmal a Sexuall y matur e mel e andfemal e (nulliparou a an dnon-pregnant ) Sprague-Devle y rat s (CD*(SD)BR ) approximatel y 8- 9 week s o f ag e vil l b s obtalns d fro m Charle e Rive r Laboratories , Kingston , I T o r othe r appropriat e source . Th e anlmal a vil l b e acclimate dfo r a t leae t fiv e day e prio r t o study start . Th e healt hetetu s o f th e animal s vil l b e evaluate dby a veterinaria nprio r t o th e ster t o f th e study . Afte r cullin g by ueue l procedures , forty-eigh t male s an d forty-eight/emale e vil l b e assigne dt o th e study . Weigh t variatio na t etudy star t ahoul dno t excee da 20 Z o f th e mea nvelgh t fo r eac haex . Animel a vil l b e e t leaa t 1 0 veek a ol da t th e beginnin g o f th e matin g phase . Th e ra t va a ehoae nfo r thi s study becaue e l t i s a commo nrepresentativ e apeele a fo r toxicit y etudiea . Thi a atrei nha a a hig hfecundit y endi s routinel y

uss d i n roden t reproductio nen ddevelopmente l toxicit y studies . Th e re t i s on e o f th e tv o primar y

epecle e recommende dfo r us e l ndevelopmenta l toxicit y atudle a by U.S . EP A

andOEC D guidellnea . Housin g Anlmal a vil l b e house dandexpose dt o th e tes t materia l i nappropriat e arsa s o f th e vivarium , HAEL . Durin g th a acclimatio nperiod , anlmal a vil l b e houee d by ae xi ngroup a o f five l neuapende datainlea a atee l vir e mes hcages . Durin g th e exposur e periods , anlmal a vil l b a house dsingl y i n multicompartmente d etelnles s stee l mes hcagea . Startin g a t etudy

initiatio nandcontinuin g throug hth e prernetin g period , animal e vil l b e houee doingl y durin g nonexpoeur e period s i nsuspende d steinles s stee l mes hcegee . Durin g th a matin g period , th a animal s vil l b e house don e mal e vit hon e femal e durin g nonexpoeur e perlod a i nauapende d etelnlee e etee l mea hcegea . Follovln g th a matin g period , mel e en dfemal e anlmal a vil l b e houee dsingl y durin g nonexposur e period s i nsuspende d atainlea a stee l mee hcages . O no r abou t th a 19t hda y o f gestation , soli d bottom pan s containin g beddin g materie l fo r nestin g wil l b s pu t i nth s nonexposur e cage a o f th a femal e rate . Targe t level a fo r expoaur e an dnonexpoeur e environment a ar e ebou t 2 2 a s 3* C end30-70 % relativ e humidity * Reletlv a humidit y level a ma y

briefl y b e outaid e o f thi e rang e durin g cleanin g procaduree . Timer e i nth e etudy room a vil l b e programme dt o provid e a photoperlo d o f 1 2 hour s fro m 6 e m - 6 pm . R o othe r animal s vil l b e houee di nth e eas e roo m vit hthi s study . Csges , recks , and feeder s vil l b e veehe d onc e pe r veek . Abaorben t pape r unde r th e cage s vil l b e change da t leas t thre e time s ps r vee k durin g th e premating , mating , an d geatetiona l periods . Beddin g materie l l nth e soli dbottom pan s vil l b a change donl y

i f neceaaar y

durin g th s post-partu m period .P. 6

BAEL-MT6215 T Pag e 5 o f 1 1

P«« d an

d Wata r Agvay * Prolab " Anima l Die t (RM H 3200) , certifie dgroundcho v vil l b e availabl e a dlibitum , durin g nonexpoeur e perlode . Municipa l ta pvate r (Monro e Count y Vate r Authority ) vil l b e supplie di dlibitu m durin g nonexpoeur e period e throug ha n automati c vaterln g eyetem o r i nglee s bottle e vhe nthe neetin g pan e er e l n th e eagee . H o knovncontaminant s ar e expecte dt o b e preeen t i n th e fee do r vate r vhic hvould'interfer e vit hth e outcome o f th e etudy . Th e vete r l e analyse dfo r contaminant s o n a quarterl y basis . Identificatio n Al l adul t rat e vil l b o identifie dby uniquel y numbere dmote l ee r teg e en dal l adul t mal e andfemal e rat a vil l b e aesigne da etudy numbe r vithi ndoe e groups . 

### Randomizatio n Cullin g an

drandomisatio no f th e animel e vil l b e don e b y computer-generate d liat e ueln g th e Automate dAnima l Toxicology System (AAT8) . Th e mele s an d female s vil l b e eeelgne dt o th e etudy group s o n th s basi s o f body vsight a a o tha t the mea nbod y

veight e er e almila r amon g th e group a a t th e etar t o f th e etudy . Animel e receive dvit hth e initia l ehipment , bu t no t use dl n th e study , vil l b e remove dfro a tb e etudy room:a t th e star t o f th e treatmen t period . Record s vil l b a kep t documentin g th e fst s o f sl l animal s rscelve dfo r th e study .


### STUD YPESlfif

l Iriitmtn t graw i Th e animal s vil l b e assigne dt o thre e tes t group s anden s si r contro l group , eac hcontainin g 1 2 mal e an d1 2 femal e rets . Thi s grou psls e ve s chose nl n orde r t o yiel dapproximatel y sigh t pregnan t fsmsls s fo r study i nth o absene e o f a n advere e reproductiv e effec t produce db y th e tea t article .
Exooaur a Condition * Th e inhalatio nrout e va a choee nalnc e l t l a a possibl e rout s o f expoeur s fo r ma nan dve s recommende db y

th e U.S . EPA . Exposure concentration s vil l b e selecte dbese do n th e result s o f a preliminar y inhaletio nstudy

I npregnan t femal e rata . Th e concentration a vil l b a include dl n • protoco l amendment . Th e highee t concentratio nehoul dreeul t i ntoxi c effect s bu t no t produc e mortalit y

i nth e parenta l anlmala . Th e intermediet e concentretio nahoul d produc e minime l obeervabl e toxi c effecta , andtha loves t concentratio nleve l ehoul dhav e a lov

probabilit y

o f producin g toxi c effsett . Excep t fo r treatmen t vit hth e tee t substence , animal s i n th e contro l grou pvil l b e handle dl n a manne r Identica l t o th e tea t anlmala .P. 7

• uv i r- . u i

BAEL-MT6215 T Pag e 6 o f 1 1

Evpoaura Condltlon

a Cont . Exposure a vil l b e fo r ei xhour s pe r dey , seve nday e pe r veek . Bxpoeure e vil l b e conducte dl n 42 0 L etalnlee e etee l an dglae e inhalatio nchambers . Chamber s vil l b e maintaine dunde r negativ e pressur e (0. 5 Inc hvoter ) vit h1 2 t o 1 3 si r change a pe r hour . Vepor s vil l b e generate db y meterin g th e tes t materia l dropvls e Int o a glas s bead-packe dcolum

neupplle dvit hmetered , dried , oil-fre e compreess dair . Chambe r vapo r concentration s vil l b e determine da t leee t onc e pe r hou r usin g a MIRAN * IA

infrare danalyse r equippe dfo r automate dsamplin g an danalysis . I naddition , temperature , humidity , an dsirflo v

i nchamber s wil l b s monitore d andrecorde da t leas t onc e ever y hal f hour . Nomina l chambe r vapo r concentratio n(rati o o f volume o r mas s o f tee t materie l uss dan dtota l airflow ) vil l b e calculate ddally . Anima l cag e eeelgnment s vil l b e rotete d dall y vithi nthei r respectiv e chamber s t o minimis s potentia l positiona l effecte . Distributio no f th e tee t materia l vil l b e determine dinitiall y b y measuremen t fro

m numerou s position s throughou t eac hchambe r an dvil l b a compare dt o tha t o f a fixe dreferenc e pee l tio nvithi neec hchamber . 8ubeequently , el l tes t dat a vil l b s rscordo dfro m th s referenc e poaltlon . Duratio n o f Treatmen t Th e etudy

i a compose do f fou r phaeee s premetln g (1 4 daye) j matin g (upt o 1 4 days) ; pregnanc y

(21-2 2 days) * andsarl y lactatio n( 4 days) . Female s wil l b e expose donl y

unti l De y

2 0 o f geetatio n(approximatel y 55-4 8 expoeuree) . Al l mel e rat a vil l b e expoee dthroughou t th e entir e study , a perio do f epproximatel y

40-5 3 daye . Male s vil l b e expose dunti l th e de y prio r t o euthanaeie . Male s vil l b s euthanatize dafte r las t litts r ha s bea n euthanatlsed . Exposure e vil l b e conducte do n e ssve nday/vee k beela . Matin g Mele e endfemele a vil l b e mete dlt l vithi nth e eas e dos e group . Female a no t lneemlnate ddurin g th e firs t wea k o f metin g wil l b a place ddurin g a second wee k o f metin g vit ha mal a vhic hha dsuccessfull y mate dwit ha femal e durin g the flra t week . Th e ea r ta g number a o f th e mate dpair a -wil l b e recorded . Copulatio nvil l b e verifie dthroug hIdentificatio no f sperm l nvagina l smear s o r b y appearanc e o f a copulatio nplug . Th e mornin g o f th a da y a plu g o r vagina l sperm

l a obeerve dvil l b e eonsidsre dDa y 0 o f gestation . Followin g copulation , th e mele a andfemale s wil l b s sepersts dandhouse dindividuall y unti l study

termlnetlon . Bod y Walah e hataflnatlon a Th e femal e animel e wil l b e weighe do n Day e 0 , 7 , and1 4 o f th s prsmstln g period , Dey e 0 , 7 , 14 , an d2 0 o f gsststion , andDay s 0 and4 post-parturn . Th e mal e anlmal a vil l b e velghe do nDay e 0 , 7 , and1 4 o f th e premetln g period , en d veekl y thereafter . Al l anlmal a vil l b e velghe da t th e beginnin g o f th e matin g perio dan

dveekl y durin g th e cohabitatio nperiod . Al l adul t anlmal a vil l b e velghe den

dfaete dth e de y

befor e euthanaeie .P. 8

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BAEL-MT6215 T Pag e 7 o f 1 1

rea d Consumptio n
Fee dconsumptio nvil l b e determine de t leae t onc e e vee k fo r al l animel e durin g th e premetln g period . Fee dconsumptio nvil l no t b e determine dduring th e mating period . Fee dconsumptio nfo r mate dfemale s vil l b e determine da t leae t onc e a wee k durin g geatatlo nand fro m Day 0 t o Day

4 poetparturn . Resumptio no f weekl y

feedconsumptio ndeterminetion s wil l bsgl nfo r msl e animal s afte r th e 14-da y matin g perio d(efte r th e en d o f th e longee t poeeibl e matin g period) . Clinica l ObaarTatlon a Clinica l observation s vil l b e mad e e t leae t onc e deily . Obaervetlon a vil l include , bu t no t b e limite dto , examinatio no f th e heir , akin , eyee , mueou a membranea , reeplrator y eyetem , circulator y

system , snd sutonoml c and centra l nervou e systems , fecss , urins , sn d genera l activity . Poot-perturn , neonata l observation s vil l b s conducte dsimllsrly . Th s dam s wil l b s observe dfo r th s beginnin g o f parturitio nand thi s dst s wil l b s uss dt o ealeulat s th a gaatatlo n period . Al l pup a wil l b e examined , withou t hendling , a a aoo na a poeeibl e efte r birt ht o determin e th e numbe r o f viebl e sA d stillbor npupa . Th a da y o n whic hth e da m

ha s completel y

finishs d deliverin g wil l b a coneidere d post-pertu

m Da y o . Lltter e wil l b e examine dfo r ebnormalltis s o n Da y o and Da y 4 poat-partum . Th e numbe r o f pup s (sliva and dead ) wil l b a counte dan d eexed . Liv e pup a wil l b e velghe de e a litte r and mea npu pvelght a vil l b e calculated . CllnlCB l EltlWlQB YIlifllnitlflD J o n HSlB S
A t nscropsy , bloo dvil l b s collecte dfro m th a poeterio r ven a cav a o f al l mal e animel e Whil e th e ret a ar e unde r CO 2 aneatheaia . Al l aaeay a wil l b a conducte db y

th e Anlme l Clinica l Analyai e Croup , Toxicologica l Scienee a Laboratory , RABL * Hematolog y

teet a wil l include 1 hematocrit , hemoglobi nconcentration , re d bloo dcel l count , and whit e bloo deel l count . Fixe dbloo damear a wil l b e prepere dand etored . Clinica l chemlotr y

teet e wil l include s aapertat e smlnotrsnofsras e (AST) , alanin e aalnotraneferae e (ALT) , glucoss , urs a nitroge n(UN) , gamm a glutamy l transpeptidas e (GGTP) , tote l bilirubi n(direc t bilirubi nma y b e measure di f tots l bilirubi ni a elevated) , creatinine , tota l protein , albumin , albumin/globuli nrati o (A/ 0 ratio) , potaaaium , chlorlda , calcium , an d phoaphorua . Urinalysi s urlnalyal s i a no t recommende do n a routin e basi s i n thi a typ s o f screenin g teet , bu t ha a bea ninclude dl n thi a protoco l baae dupo nth a knownpropertle a o f th a tea t materiel . Durin g th e wee k prio r t o necropey , mal e rat a wil l b e place dl n metebolie m cege a fo r approximatel y 1 6 hour a fo r urin e collection . Fee dend vate r vil l b e availebl e g d libitu m durin g th e collectio nperiod . Th e osmolalit y

end volum e o f th e urlne e vil l b e measured . Microscopi c examinatio n vil l b e conducte do n urinar y sedimen t fo r th e preoene e o f essta , re d bloo d cells , whit e bloo dcells , crystals , sn d bactsrla .PJ L 3 • u u n u . uu xr .0 3



### BABL-MI6215 T Pag e 8 o f 1 1

Wicropi Y Animal s tha t di e o r sr s euthanatize dbeeaue e o f morbidit y wil l b o nscropsls d a e aoo na a possible . Survivin g mal e an dfemal e enimel e wil l b e aneethetlse d wit hCO2 , andexsanguinate dby coverin g th e posterio r vsn s cava . Al l animal s vil l b s fssts dovernigh t prio r t o schedule dnseropsy , an dbloo dvil l b e collecte dfro

m mele e fo r anelyal e prio r t o exeangulnatlon . Al l adul t animel e vil l b e aubjecte dt o a ful l necropa y vhic hInclude s examinatio no f th e externa l surfac e o f th e body , al l oriflce a andth e cranial , thoraci c an d abdomina l cavitie s en

dthei r contante . Specia l attentio nwil l b e pai dt o th a organ e o f th e reproductiv e system . Femala a tha t fal l t o litte r wil l b e euthanatize dapproximatel y fiv e day s afte r thei r expeete ddeliver y dat e and th e uter i vil l b e examine dfo r implantatio naite a andcorpor a lutaa . Dam e the t litte r vil l b e examine dfo r implantatio nsita e andcorpor a luta a a t th e time o f necropsy . Dea dpup a endpup s euthanatize de t terminatio no f th e study vil l b e examine d maeroeeopieall y

fo r externe l ebnormslltlee , bu t no t nscropslsd- . Tissus a fro m th e offsprin g vil l no t b s collected . We t weight s o f th s livsr , kidneys , thymus , lungs , testes , an depididymide s vil l b e collecte de t necropsy . Palrs dorgan s vil l b s velghe dtogethsr. Organ/body weigh t ratio s wil l b s calculated . Hlatopatholoa v 

### Th e tiesus s lists dbslo v

sndtissue s fro

m terge t organ s identifie ddurin g necrope y exeminetio nvil l b e collecte dfro m al l adul t animal s andrateine din epproprlat e fixetivea . Th e tiaaue a t o b e collecte di nbuffere dneutra l 10 X formali ninclude s live r ( 2 sections) , kidney s ( 1 section/kidney) , adrena l glande , brai n( 3 aection a Includin g msdull s oblongata , pons , cerebella r » cortex , en dcerebra l cortex) , heart , epleen , thymus , lungs , naaa l paaaegea , ( k



### - xxa 

### ^' overiea , andtarge t organs . Th s tssts s sndspidldymids a wil l b s preeerve din Bouln' s fixative . Histologica l evaluatio nwil l b a conducte do a th a tieaue e Hate dabov e fro m contro l andhig hdoa a sal s andfemal e animals . I f ebnormalitie e o r equivoca l result s ar e eee nl naa y

o f thes e tissues , th a asm s tissus a fro a lows r dos s group s wil l b s examined . Rletopathology vil l alao be'performe do a th e organ e andtiaaue a Hate dabov e fo r al l adul t animel e vhic hdi e o r er e euthanatize d prio r t o study

termination . Histopathology vil l b a performe do nsignifican t gros s lesion s i a al l adul t animals . Ovarie s fro a sa y salaa l vhic hfell a t o complet e it s pregnanc y

vil l b e examined .P.1 0
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HAEL-MT6215 T Pag e 9 o f

1 1

fiTATTSTTCAL PBOCRDUBE g Mea nvalue e vil l b e calculate dfo r chambe r coneentretion , chambe r temperature , chambe r relativ e humidity , edul t bod y veight , feedconsumption , cllnice l laborator y

determlnatione , orga nweights , geetetlo nperiod , litte r else , pu p body veight , pupbody

veigh t gala , andpu p% survival . Al l mea ndata , vher e Applicable , vil l b e evaluate dusin g th e following computer-generate d etatietica l teste » Bartlett' s tee t ( p< 0.01) , one-wa y analysi s o f varianc e (ANOVA ) ( p < 0.05) , an d Duncan' s multipl e rang e tes t ( p < 0.05 ) t o indicat e etetistica l significsncs . Batlo s suc ha s Xmortalit y andXpregnanc y vil l b e compare dueln g Ch l Squar e Tebles . Transformation s t o normalis e dietributio no f th e dot s vil l b e performe dvher e appropriate . A t-tee t ma y

b s performe dvher e th e Bartlett' s tes t lndlcete e e significan t differenc e i n variance e vhic hmigh t Interfer e vit hinterpretatio no f analytica l reeults .

ftATA ZTOfUe E Th e fina l report , dat a eheets , sn del l non-perlehabl s re v dat e vil l b s stors d i nth s HAE L srchlvs s fo r a t lees t ts a years ,

REPOR T Th e fina l tss t repor t vil l includ e a deecriptlo no f th e material s andmethode , th e reeults , en

da discussio nsa dinterpretetio no f th e reeults . Th e repor t vil l ela o includ e th e epeelee/atral no f rat i abnorma l clinica l eign e (day o f observatio nandclinica l couree) } da y o f deet ho f el l animal s includin g thos e survivin g t o study

terminations , a summary o f th s numbs r o f implentetlone , litte r siz e sndaea npu pweights } toxi c offset s o n reproduction , offeprlng , an dpoetnete l grovth } body endorga nveigh t dat a o n al l parenta l animele } fee d coneumptio ndata } hematolog y en dclinica l ehemietr y

reeulte } necrope y findinge } hlatopatholog y reeults ) an

detatietica l treetnea t o f th a atud y reeulte . Summer y table a include dl a th e repor t vil l preoaa t th a followin g date s Exposur e condltlon a Numbe r o f anlmal a a t th a star t o f th s tss t Fertilit y

indice s (mel e en

dfemale ) Materna l mortalit y Numbs r o f viabl e litter a (Geetetio a Index ) Mea ngeetetio a perio da B B lumbe r o f totall y

reaorba dlitter s Mea nmaterna l bod y

velght a « B D Mea nfemal e bod y

weight s s 8 0 (prio r t o pregnancy ) Msa nmal e body

weight s * 8 0 Mea nmaterna l bod y

weigh t chang e durin g geetatlo a a 8 0—. . P.1 1 KODA K 32 0 It L N O

. ab-/22-u^ y De c lU.y o 9 = 5 5 No.00 1 P. n

BAEL-MT621S

T Pag e 1 0 o f l l

Summar y table e cent . Mea n fee d consumption fo rmale sa d femal e enimel e durin g th e premetln g perio d s S

D Mea nmaterna l fee d consumptio ndurin g gestatio na S D Mea nfee d consumptio nfo r mal e enimel e durin g the poetmatin g perio d t S D Mea nnumbe r o f live pup e o n Day e 0 ea d 4 poet-partu m * 8 D Mes a litte r els e (live + dee d pups ) o a Da y 0 poat-pertu a ft 8 0 Mea nnumbe r o f dea d pup a o n Da y 0 poet-partu a a 8 D Mss a y pu p survivs l o n Da y 0 poet-partu a ft 8 0 Mea nXpu p eurviva l fro m Day e 0- 4 poet-pertu

m a S D (Viabilit y

Index ) Mea npu p body

vaight e o n Day s 0 sn d 4 post-partu

m a S D Hea a pu p body

veigh t gal a Day s 0- 4 post-partu m « 8 0 Se xrati o fo r pup e o n day s 0 sa d 4 Mea nmal e hematolog y

value e a t nserops y

a S D Mea nmal e clinica l cheaietrle s a t necrops y a 8 0 Individus l dst s vil l b s preeente d i n th e appendlce e end vil l include s Individua l femal e body veigh t - pregnan t female s Individus l femal e body veigh t - non-pregnan t feaals a Individua l mal e body

veigh t Individus l fss d consumptio n- prsgnan t feaals a Individua l fee d consumptio n- non-pregnan t fsaala s Individua l fee d consumptio n• male s Individue l reproductio nan d litte r dat a Individua l aal e hematolog y dat a Individua l mel e clinica l ehemlatr y dat a Individua l groa e pathology dat a fo r adul t animal s Individus l histopatholog y dat a fo r adul t anlmal a Individua l groe a abnormalit y dat a fo r offeprln g Chemica l purity , etebllity , an d concentratio nanalyae e repor t

PaftJKCT FAtTTCIPAHT g Study Directo r Walte r J . Kraeavage , U.S . Stud y Technician s Lle e G . Bernard , A.A.S . Beed e A . Moulto a Heaatologlat/Cllalca l Chemle t R . B . Emmons , E.g . Psthologia t Mila n8 . Vlaovle , D.V.M. , Ph.D . Laborator y

Anima l Medicin e Gordo nJ . Hankinaon , O.V.M. , M.S . Analytica l Chemis t Kennet hA . Roblllard , Ph.D .

RIOBBJU I Proposs d OEC D Guidelin e fo r Testin g o f Chemicel s (1990) . Combine d Repee t Doe e end Reproductive/Developmenta l Toxicit y Screenin g Teet .P.1 2
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### SIgBATUR E PAflB HABL-MT6215 T Peg e 1 1 o f 1 1

Study Directo r Dat e

Director , Memmelie nToxicolog y Section , BAE L Dat e

Director , Toxleologice l Science e Laboratory , BAE L Dat e

HAB L Quellt y

Aeeurenc e Uni t Dat a

Sponeor' e Repreeentetlv e Det e