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# 138)11-1-1 8 Docket Number: 

# A-83-2 2

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Sheet 138 of 162

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OI LADDITIVE S \\. \\. BALDWIN . C.l . n'NXINCHA. M AN D I) . I'HAT T From tin- ('itncir l.'i'xitinh

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('iillrijr af Suri/ttiii.s. Lanihiu KI'I'I-JVIM I I' i i r|Hll.li.-a t LH , .In k -.1 . Mifi l PKKVK M si. vi twa s reporte d tha ta proprietar yengin e ni l additiv e wa s carci iTiit'ciii' - followin g ri'|M-atri l ski n pain t ini : i n i n in - ( I l a I d win . ('unninghai n an d I'ra t I . Iiiili) . T h i s additiv e whic h i s utilize d a s a hig h pressure . hig h temperatur e lulirii-aiit . contain s a formulatio n consistin g mainl vnl'lea d naphthenat e togethe r wit h siiii'l l ainiiunt s c l chlorinate d hydrocarlion s suc h a s earho n tetraehlorid e o r \ | : I -triehlnre t h.-in e disperse d i n a ininera l oi l hase . Th e variou s eoinponent s ,i vthemselve s highl yhelerngeiieiui s mixture s withou t an ywel l define d eharac i.-ri.-ties . Thu s th e lea d naphthenat e fractio n i s a sulisiiliar yoi l produc t ..i.iaiiiei l durin g th e 11: ; 111111".- 1 < -1 ur e o fhyilrocarhoi i distillates . Thi s fraction . , T:;:<•1 1 i s o l varyin g co m po s i tio n dependin g upo n th e sourc e o fcrud e oil . contain s •.-tt i salt s o fa comple xmixtur e o faromati can d aliphati ccarhoxyli cacid s Kiiniiici'iis . I!i"i7) . '!car! ytherefor e isolatio n an d chemiea l characterizatio n o f ;:; rcarcinogeni ceon , j.niien i ( s ! i n th e proprietar yoi l add i I i \ es . al t houg h desirahle .

. n.i t practica l a tthi s time . Howeve ri twa s considere d essentia l t o ascertai n •,i-i.-llie ri ii e carcinogeni cac t ivi l vwa s associate d wit h an von e o fth e crud e pro - -„•:.- . par t ic i i la rI vi n vie wo | th e varie tvo l uses . e.g . pain t driers , woo d preservative s • ; , | u i- t 1 in g agents , o fI h e n a ph i hem e acids . Accordingly . \ ali o u s component s o f • •• •ni l ad d i t ive . supplie d h vth e m a n u la d urcr . h a \ e hee n assesse d lo rcarcinogeni c • : \il vfollowin g ski n pain t IIIL ' i n mice . I n addition , a secon d proprietar v : .|jtjvi •utilize d inaini va - a n uppe rcylinde rluhrican t ha s hee n teste d fo r •I . iiingenii - ac l i \

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< _\'lililin I. ('uiilpoiieii l fraction s o fth e additiv e previoiisl vshow n t o li e .T.-iimgciii cfo rmous e ski n (|!al,l win . ('uuningha m an d I'ratt . I !Mil ) wer e supplie d ' • 4 ih e manufacturer . •! •Has e oi l int o whic h th e additiv e i s dispersed . •ii ) Additiv e formulatio n •'flu - proprietar yadditiv e contain s | u pe rcen t oi ' ••. formulatio n i n has e oil . fo rcarcinogeni cassay , th e formulatio n wa s ski n ...:i,ici l a s a - 1 1 pe rcen tvvsolutio n i n doiilil e distille d Al ! Iienzene . •jii ) Lea d naphthenate . Thi s material , supplie d a s a dar k drow n oil vliipiid . ..!,. •n l t h e majo reoinponent s o l th e additiv e formulation . Lo rcarcinogeni c

.. ,-, . th e materia l wa s ski n painte d a s a i' n percen t vvsolutio n i n Iienzene . .\ii'lili''' II - Aproprietar yadditiv e agen tuse d mainl ya s a n uppe rcylinde r .'Mi-ant . Thi s wa s ohtaine d commerciall yi n seale d cans . :' l 

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-.5 > KNI'KKIMKNT.VI . I'K i H'Tflifl' K Youn g adul tmal e The ywer e maintaine d i i libitum. alhin o mic e (Seholiel d strain ) wer e employe d i n al l tes ' standar d ciihe d die twit h water ' i group s o fJ u o n a Dorsa l hai rwa s remove d wit h electri cclipper s a tth e lieginnin g o feac h tes tan d the n subsequen tI vw h el l lleeess a r y . < h i sample s wer e applie d dm ) ivvis e t ' t h e ski n fro m all-glas s tuhereiili n syringe s an d wher e necessar ysprea d wit h gla.- - rods . Mic e wer e tre a te d onc e o rtwie e weekl vfo rperiod s o fu p t o I '2 mou th s an 1 ' t h e tota l dos e iipplie d i s show n i n Tabl e I . Mic e wer e examine d fo rtumou r -kl vinterval s unti l th e test s •r e terminate d (I s montlis ) an d killc u whe n the vwe r e il l o rwi n n tumour s wer e considere d malignant . Al l tumour s we n take n fo rhistologica l examinatio n an d tumou rincidence s wer e assesse d fro m ti n numbe ro fn lic e survivin g (a tri.-k ) whe n tumour s wer e firs tobserve ' 

### 'I " KKSI'I.'I' S i e bas e oi l fractio n use d i n th e addi tiv e pre vioiis l vsho wn t o b e carcinogciii 1 ' (additiv e I ) prove d t o b e highl ytoxi ccausin g marke d inllaminator vchange s i n Durin g th e firs t( 1 mmi'l e ski n simila rt o thos e uliser ve d wit h th e whol e addi ti i ftreatmen twit h thi s fraction , mi , ; m painte d twie e wi 

## I I owevrl' . surviva l wa s poo r r . M i u l tin - origina l mic e (i n pe rcent ) dvui g o r bein g ki l ( fig . I ) an d ther e lor e mic e wer e I re a le d I here a Ite ron b onc e weekl ymi l i l ski n pai n tin g wa s terminate d ( I _ ' mon i h-.) . Nei l he ro fi h e o i he ri wo trac tion.. . o fl h e additiv e showe d an vtoxi cpropertie s 1 (fig . I ) despit e i h o wa n ac l tha i th e 

### I s s k i n am i surviva l o ftreate d m i c e wa. - ge m l b.-t ; v

ver e a | ipln-i l I wic e w , •l: h •' ' itration s doubl e thos e i n th e whol e addiiiv i T h e I ias e oi l Ir a e l io n pro ve d t o h e carcinogeni cfollo win g repeale d ski n p a ni l i c inducin g ski n tumour s i n M i pe rcen to l mic e a tr i s k (Tabl e |) . Althoug h tl i t i n tumou rincidenc e i > coi n par ; l o tha i iiid u wit h t i e wliol e a Mnr . ((ii i pe rcent) . th e m a jori tvo ftunio n i s wer e benig n p a p i I Ioni a l a an d squamou s cd : carcinom a t a ( f I g . -) v i er e observe i Il l onl y. i mic e I I , pe rcel l 1 I . T l n s contra- ' wit h th e hig h incidenc e o fski n earcinomat a induce d b vth e whol e additiv e l- d p e rcent) . .Neithe rth e whol e additiv e formulatio n no rth e lea d naphthenat e bactiei i produce d an ysignifican tcarcinogeni crespons e i n mous e skin . Henc e ski n

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# V I'AKCINOCENI C KNCIN KOil . ADDITIVK S ;i0: > ohillmiiat a wer e observe d i n onl y2 mic e ( 4 percent ) follo win g ski n paintin g wit h Vji d inphthciiat cwhils tonl ya singl e papillom a develope d i n mic e treate d wit h tin - whol e additiv e forniulatio n (additiv e concentrate) . However , ski n paintin g •ii - lea d naphthenat e fractio n induce d marke d kidne ydamag e an d tubula r ,.icii<iinat a wer e observe d i n 4 mic e whils tone.ha d a rena l carcinoma .

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Additiv e II . unlik e th e lirs tpreparatio n tested , di d no t induc e ski n ulceratio n .ii- l mi.'. - tolerate d twic e weekl vtreatment . Thu s whe n tumour s wer e lirs t ,,-•..nie d ii' 4 weeks ) onl yl i mic e (I n pe rcent ) ha d die d o rbee n kille d (fig . I) . !Vi- . additiv e als o wa s carcinogeni cinducin g ski n tumour s i n L". I (i s pe rcent ) o f ii,in - a tris k

(Tabl e I) . Thes e tumour s wer e mainl ybenig n papillomat a bu t ,|ii.un.ni s cel l carcinomat a wer e observe d i n I n mic e (11 1 pe rcent) . 

### Discrssiii N Th e presen tfinding s clearl ydemonstrat e tha tth e bas e oi l componen tofthe . .,i ! additiv e previousl vteste d (Baldwin . Cunningha m an d IVatt . liMil ) i s th e onl v ji.nii. u wit h an ysignifican tcarcinogeni cactivity . Whils tth e ac tivi l ie s o fth e ',..:-.,• oi l am i whol e addi ti ve wer e almos tiden t ica l whe n assesse d fro m th e incidence s 

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"ilM i K . \\ . UAI.DWIN . r.. .1 . CI'NMNCH.W I AM ' I" . CHAI" I o ftota l ski n tumours , th e incidenc e o fski n caieinonial a wa s signiliean t I v|., m • ' i n mic e treate d wit h bas e oi l (Tabl e I) . Thi s differenc e ma ys i mp l vb e du e i, , 11, . poo rsurvi va l o fmie e I reate d wil h bas e oi l (fig . I i . althoug h th e po.-.-ihili i v' * .. i othe rcomponent s i n th e additive , e.g . halogenate d hydrocarbon-. , pus-,-.. - pi<, u • in g propertie s canno tb e e\cluded . Ilowevei- . th e findin g tha t th e whol e ; 11 ! •1 1 > i \ •• forn i uia t io n excludin g th e bas e oi l an d I h e lea d naph l henat< - I r. n tio n wen - uia<- ' i \ • implie s tha tcomponent- , i n ih e bas e oi l ar e niainl vre-pon-il,! e fo rth e ear . iu. > •• icit yo fth e aihli t i ve . I're vion- I v. th e ba- e oi l wa- , ci a s- i lie d a - a \ eieziiela n crud e ni l whic h h. e I undergon e I hernia l refor m ing . I n vie wo l l h e pre - -n i I in d nig- - lur i le r. h. u i . i" ' is tie s o fth e bas e oi l hav e bee n pro vide d bvI In - m a 1 1 ul a e t nivr « an d I le- e i:,.!; , ' : • tha i i ti s a spindl e oi l .Moreover , it - phv-i'-a l propertie s -u^' 1

. - I tha ti t !•' - withi n tin - ,| a —o | ml - whic h Iro m pn- vion - -Hide - iTwoi t an d I. vi C I''.':. . Cook . I'arru t hel - an d WIlloll- e I ••-~» —1 ma vb e expecte d l o li e e.,re| | I,| , Detail- , o fih e n>iii|i,i-i i io n o fI h e secon d addiliv e (additiv e II ) whic h !,. •I i , sho wI I t o li e e. l ni l lo g elli e (T a bl e I ) ;ll e Ho t; l V; l i I. I I li e . I lo wC Ve r1 hi. - addi ' ' Ve , d . . contain - a Iormula l io n di-per-e d i n a muicr. d oi l ba-. e an d li e po-alah l , I*.. I I h e carcinogeni c- i 1 1 •-1.111 1 , ~ o i ••c n i t a ine d i n I hi - I t ac tio n : d s l o li e , . a,-id - ; c l Clearly , a large r-ere - n\' oi l addiiive s an d ihei rcomponent - i-eipiu-' - l " '• • ev a lu a I ci l i n n i de l |„;|..,.. , I I n •| T , . - - . j I ii , po t e n I ia l hea l I i i ha/.-ir d o t tle- e -id, - i.u, , •• Moreo ver . althoug h I le- e experimen t a 1 ii i i d ing. - ar cno i din-e l I vapplicabl e i n ma: . i n con-idcrm g ti ci-llr , l - o l oi l additive - an d ai.- o lubricatin g oil - i n genera l li " v nee d t o In - eoii-idere d a - p o —ibl catmospheri cpollulan!-• . resultin g Iro m en,i--i i a s oi l particle - i n vehicl e rsh.-iu- l fume- . Whil.- I li e amoun t,,( ' oil vmati-ii 1 ' emitte d ma vonl vb e -mai l compare, ! t o tha t o l th e petroleu m ,, o , 1 1 o ; - : i..: . product.- , althoug h ihi - wil l depen d upo n th e el'ieieie yof ' th e engine , ti chi_ " eareinogenici t vo fadditiv e I an d ii s bas e oi l ,u,_.e,.s|. - tha t ,-ue h materia ! HM V represen ta -igiiilic.in i carcinogeni cfactor . Wynde ran d I lotVi n in n il'.a'il' : C v deinoii.- l rate d tha ti -1 1 •

_n o e\hau- t condeii.-ale.- . prepare d s o iha l muc h o | th . ..i. v materia l via - exclude d an d - " presumabl ycontainin g mainl ypetioleiin i eomlm tio n product- , wer e carcinogeni c|,, rmous e -kin . Whils tdirec t compaii-o n •• ! thes e s i u d ie s wi th tI n •presen t finding. - i. - complicate d b vv.-iria t ion. - i n i-. xperiiueiii.i l procedure , tin - carcinogeni cre.-pons e elicite d b vadditiv e I approximate - |, , tha t o fth e mos tpoten tcondeii.-al e traction . Tha tai rpollutant - represen t a signiliean tfacto ri n environmenta l i-an-in o genesi s i s no wwel l esi.ililishe d (1 1 nepe r. / nl.. I'.MiJ . fal k

an d Ixotiu . IIHlL' . Koiii . an d falk . I'.Mi!! ) an d severa l polvcveli ch vdiocaiboi i carcinogen s hav e IM-I-I I detecte d i n urba n pollute d atmosphere.- . (Ixoti u an d falk . I'.Hi!!) . A s ve thoweve i th e significanc e o fminera l oil s a s environmenta l carcinogen s ha s no t receive d sufficien tconsideratio n althoug h numerou s .-Indie s hav e demon- l rate d ca n li e geni e activit vi n a variet yo flubricatin g an d cuttin g oil - (Shubi k an d S.illeii . Iil.il ; Cihna n an d Vcs-clino vi l ch . I'.Cili ; Kckardl . I'.CiT : Coo k .('arru tIn i - am i Woodhousc . I!I."IS ; llueperan d I'avne . I'.MiU) . I n considerin g t h e ca i einogenei t v o fpetroleu m derivatives . Huepe ran d I'avn e il'.Hiii ) hav e als o enipha-i/e d ti e poten t ia l he a I th hazar d o fre s p i ra l o rvexpo-ur e t o eo n I in g an d lubrie.i t in g oi l nn- i - KXI'I.ANATlu N <'!• ' I'I . \ ll- ! Ke . L' . Aililii m I Im - I in,In.c I -.|ii ; i s ,-T-l l .•in..in..iii.- i wit h I.T.-.-I I IIIM KI I vI- ! Ju l i .

### CAKCINOCKNI C K M : INK oil . AKMTIVK - 5 1 r, ietl i inspecia l occupationa l group s suc ha s metallurgica l worker s an dals o i nth e i.emulatio na t

large . However , evidenc eo f th e influenc eo f

occupationa l exposur e •, i nil mist s i s stil l inconclusiv e(Hendricks . Collings . Donley . Carret t an dRather , ;inij ) an dclearl y ther ei s anee dals o fo r amor ecomprehensiv eassessment , ofth e iia/.ai'd s o

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aproprietar y engin eoi l additiv e iirr v ioiislv ' show nt o b e carcinogeni c fo r mous eski nha s denions l rate dtha t th e .•;iiviiiogcni c substance s ar e containe dalmos t exclusivel y i nth e bas eoil . 2. Afurthe r

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als o in-livedt o b ecarcinogeni c fo r mous eskin . Th e significanc eo f t h efinding s ar e dis cussed , particiilarl v wit hregar dl o th e possibilit y tha t thes esubstance s ma y b e atmospheri c pollutants . Thank s ar e du e t o Mrs . ,M. I'. . Marshal l fo r skille dtechnica l assistance . Thi s Investigatio nwa s supporte db y abloc k gran t fro mTh e Urilis hK mpir eCance r Campaig nfo r

Uescaieh . 

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