Document kmO0wmL2RndkZ9v4m01dEEkZD

FILE NAME: Phenolic Resins (PHR) DATE: 1945 Apr 30 DOC#: PHR035 DOCUMENT DESCRIPTION: Unpublished Report - The Carcinogenicity of Bituminous Compounds, Literature Review ft wOV*'wl >"^*''"' ^ TOI CABCINOQXSICITT 07 BITOMIHOOS C0MP0U1DS *# Litr*taro loria* April 39, 1913, tM ta lM l * M * m l D lrlalo* ! k t T n i Po m t l r Torli P i t i Za tow o f th# insana# aaooat f pabllaha ln fo sn a tlo a oa Tarlo# phaaaa o f tho acne or probi* i t ahould bo Mphaalsod th a t thla llta ra ta ra rari firn # only a rapi sarray f aralopnonta la th# f ia l o f aaaoor raaaaroh aa oppila lr a a tly to th# patrolaaa, aool tar, o l i ahola oa o lila inatrio#. I h lla l t lo far fra* baia* #onpl#tn, yot l t la ballar# that a o a t o f tho la p o rta a t oorfe la th la p o rtin o la f i al haa bona aoraro, o lth or la tho roport l t a a l f or la orno o f tho h lb llo fr n p h la a l r a fa r enaaa c lr a a l a tho appaadlz aa roforro to a t th# bottan o f pofa 1. M. P . 80M THI CARClNOQtlICm 07 BITOMICUS COMPOOll* I t baa lo baan W i n d bat tba la .ld a .c a o f abl ( U ,, r i . reatar a orbar 1 artaln lnduatriaa and " tl0Ba tba a tb jopu latlon aa b olo. A ttaatlon f t r r * diraotad 1 17*7 to tb .r y blb dMtb. rat# M u lti ncm M*M1 o f .h tM .T . . . ! t t 1 . olbt ( U H o r . M -K 1 tb M . ,, r t .r a tba In t b . ( .a r a i oublia U fc lM i, " I t a lt^ l gtataa tb . ra tio o f aaaaar h i h U U n n M ` 1* *m M * t t "' 9f tua gasara,i p op ala^atlaa^ . tm aM C tlM llr a ll aaaaa U l> tlMl . r o ta that la attaakadi th ia la ala tha a lta la o l a a p la a w V Mar diaauaaaA la ta r . arhara U othar la ia a trla a aoada U .llr a a t aoataat lt t u w , p lta ta o , ahala a lla , a ta . l i t o l a a i a high laaiAamaa a f ahfta aamaar, fa r a n a d ia , llo r a r a I* W i> hrlgaattaa, ta r roaflag aaa fraoarratiraa, r U f U w fta laaalatlag aearpeaada, ahala prohaat, ata* Pi U a gita a f tha r ta o p itta a a f tha para a g g ir a ti y tha aaiaa a f ; .; mot am til ra la U ra ly raaaatiy th at O to U lahorataiy amimi* t r t h r l h * im a itlg ata ia ta U a a a 1 (ur; ttaalarly airar*!!* rariava a f th ia M fc * 4 t v* 14.29, 3 t - , T i, *71 a f tha I a t i ornai Oamaar Zmmt&tmta aararlm# f ^r- -2 - ^ which 1A9 are T9 .orted to be carcin ogen ic^ !. L. F. Flcaer our knowledge in th in f ie ld aa f o llo w s ^ ! Aa Judged b7 e l l ^liable data fo r the production of ifcln end auboutasaoua tunora in rata and n ic e , s th y lobolanthrene probably la the coat potent o f the known ohenioal otrcinogans. Systaatatls atudiea of synthetic sod el compousda hare shown tha&.the eth y l group la o f no laportanoa to tha functioning o f the ooupoundt that much, i f not a l l o f tha e ffie a o y o f cholenthrene la retained In the analogoue hydrocarbon 5.10-dlciethyl- 1 . 2- bsazanthraeene; and th at the oat a lg n lfle a n t atruotarai feature of cholenthrene or ethyloholanthreat la tha 1,2-benzanthraoana ring ayate with a certon su b stitu en t at the aeso p o e itio a 10 IftrMethy1 -1 ,2 ben tanthree ene evokes sa r e o n a in a lee- nearly aa rapidly aa methyl shol anth r e a t, and, though i t la d ia tin a tly la sa a ffe c tiv e In tha production o f skin oanoar, tha aubstanao aonatltutea tha nearest approach in a sta p le odal eoapound to a s la a la tlo n o f tho b io lo g ic a l propo r tle e o f tho hydrooarbon o f aoro Duplicated structure A ll twelve possible ueneuethyl derivatives of tho in a o tiv e 1 , 2-bensanthraaona hero boas ayntheaiaed and tested , fo r oaralnogaalo e e t iT lt y , and o f those tho 10*tooaor la * tha oat p oten t. Tha aao^oabatltuted 9- a th y l eoapound stands next In order o f potency, followed c lo s e ly by tho 5-nethyl d e r iv e tir e , ebloh produced oarooaaa In loo lth a la te n t period abont tw ice aa lon e th a t obaorrod with 10- a t h y l - l , 2-be**anthreeene. Methyloholanthreue and benzpyrene earn be recorded aa 1,2-bansenthree anas ab ut 1tu t ad at tha noao p o sitio n s 10 and 9 , r e s p e c tiv e ly , and in w d a l eoupounde th e eowblnatlon o f ho two type* of su bstitu tion la p artian larlr favorable nulG-Diuathyl 1 . 2- baasenthreaana psodnood akin tuner* In n la a with renarkable ra p id ity and In t h is t e a t aornasaaa n e th y lcholanthrena In spoed o f a a tlo n , hooch i t la loan ...-- e ffe c tI r a whan adninlstared by anbentaneoua In je c tio n . Tha thlophana laalacn a o f th e hydrooarbon has oonparablO propertlaa* . bua tro ua attanpta have bean nadc to lo o la to tho d sfln i # oarelnogacia oanpounds In cool to r by noons o f d i s t i l l a t i o n , solvent extraction, etc?*, but c h ile very potent fraetiona have been obtained, the Individual eonpouada have bean d i f f i c u l t to coperato i naavay and Hiagap proaad tba aralnoganioity of 1 ,8 ,5 ,6 - 4 1 nnxanthpaoeno, tba f i r a t pura oaroinofanio bydoroorbon k s m . Cook, Hiaar and H aaltt 24ln 1933 ia o la ta d 1,8-banspyrana, 4,5-banpyrana and 1,2-banxanthPooana and aatlnatad th a t tba o r i* ln a l onl tir pitoh oontalnad not laaa tban 0.003* of tho potont 1,8-bana- pyrana. savaral in aaatigatora 88 , 84 , 88 bata tU a p U d t o acar- ralata oapolnoganaala t l t t fluoraaoanoa. For azanpla, tba aanaop- produolng n o ta r ia l fom ad by tba a a tlo a f A1C1# on tatrahydro- aapbtbalana abona a b lu a - t ia la t fluaraaaaana, abowia* tto o o banda, 4000. 4180 and 4400 d . ., * l a b ara a ln ila r ta tba flnaraaaanaa apaotpw of 1, 8-bannantbraoana 44 Kaananay and H iasar mgg*Mt tba p o a a ib ility of tba uaa of tba fluoraaoanoa apaatrum fo r tba ppallninary azaoainatloa of atapiala auapaotad of balas auroinogaa. An lapoptant fa a t brousbt oat by aavaral in aa a tig a to ro la tbat tba t --aaratupa to abiob a ta r , abala o l or patralaun o l baa baan aubjaotad datorminoa lt a aapolnogania a a tlT lty . la ganaral, i t would aam tb at tanparoturaa ap to 5000. aro witbout - affaet M but abara tbat tanparotura oortlnogana ara fornad, tba ______yi , u xTi M t a m a seo u l oooo. " M - S I " * lU H O tr o . u a r t a i n f u i m m *1t. t t u O f . -- m u ** oooountln* fo r T0* o f a l l aaaaa of ta r oanoor ln tba Qnltod Statoa , lis . hila tba aoka oran jrodmat aaaaaa only 04 Wblla patrolaun raalduaa r a m lt ln * fr o nodarata baat traotnant ara ln a a tira 1 ,0 , yat by parala* an la a a tlv a C aliforn ia patrolaua througb a tuba a t 880C. XOnnanay and Loltab abtalnad o aary .a t it a oaralno*an 60. - InaaUa. d la iu l p ^ affln t i l baatad to 380C. undar 50 a t a i. proaaura ..pairad aaaa aaralna*aala activ ity 101. Kennaway lik e w ise o b tain ed an a o tiv e n a t u r i a l by pas1*6 .ogrcnc through a tube f i l l e d w ith w and heated to 8XCC. 115 " * ietaon aohleved e l a ll a r r e s u lts w ith tu rp en tin e a t 650C. Aeetylene y ield s an ao tiv e produet on being passed threudh a red h o t tube 69 b u t I t a u s t be p o in ted o u t t h a t treatm en t with AICI3 a t room tem p eratu re a ls o produces an a e tiv e eoapound 61. Ou tb s o th e r head, a r a t h e t i e ln h riaa eiw * mi\m predueed by AICI3 p o ly m e risa tio n a t te m p eratu res up t o 150G. were e n t ir e ly iaaetive i t is suggested th a t the condensation products of acetylene are of a nore eoaplieated nature and probably sore unsaturated than those obtained fro a ethylene. The o areiao g en io a o t l v i t y o f t a r s depends a p p a re n tly n o t only on th e te m p eratu res at t h e i r f o r n a tio a b u t a l s o an th e o h ^ l e a l eoapound used as th e base sto ck 100. ?or example, a t a r node f r a PlAMf 350C. was f a r n o re a e tiv e th a n one f r o a tu r p e n tin e made sim ila rly , the re la tiv e potencies being 100lit* Pinoae ta rs nado a t 500, 600, 750, 050 and 950*C. had r e la tiv e p o te n cie s o f 0 , IX, 14, 100 and 04. Q & d jtlff * s y n th e tic t a r a t 100*0. reduced i t s potency fro a 100 to 65, and a t 150-160*0. i t s potency f a l l to 0 . O xidation with an aoetaue so lu tio n of O hO | reduoed the potency to 04; w ith p y rid in e as a s o lv e n t, alm ost to 0 . The a e tiv e c o n s titu e n ts o f aynthetle ta rs fo ra cry sta llin e plo ratca. the r a n a lils t f iltr a te being alm ost in a c tiv e , and the p td ra te extrem ely p o te n t. U 1* oareiaogenio, probably as a re s u lt of the high tem peratures to which o i l sh a le i s su b jected 104. However, tem peratures below 400*C. give a r e l a t i v e l y in a c tiv e p ro d u ct, 500C and above being re q u ire d -5 - Ia ngland whare high tem perature t i p i t used ia iSS m an u factu re, th e re e re men? oaaes of s k in oanoer aj*>ag th* workmen, whioh i t not the o ta e in Franoe where th e low tcmpereture product ia used. The g r e a te s t amount of in v e s tig a tio n of any type of occupational oanoer haa been c a r r ie d o u t on m J,c fp^nn era awnaey in the o o tto n mi11a o f Lanoaahlme, England. Southern and Wllaon 88 in 1982 f i r s t o a lle d a t te n t io n to th e ex c essiv e oeourrenee of oanoer in mule s p in n e rs . Women w orkers a re n o t a ffe o te d and about j 70* ot 111 n in u le spinners ia of the eerotam 84, apparently . due to the f a c t t h a t a mule sp in n e r a t work wnlka to and f r o in front of h is machine, lean in g over th e moving frame fro tin e to tin e to jo in up broken ende o f th e y arn . The base o f th e frame i s on le v e l with the g ro in end th e sp in d le e on th e frame ee th ey ra p id ly revolve throw o ff o i l ffo a th e ir bear Inga onto th e e lo th e a . In tha hot m ills th e aen p e rsp ire f re e ly and eo wash o ff th e n a tu ra l | grease of th e a k in , th u s allo w in g th e o i l cL cser o o a ta o t 18 . (' I r r i t a t i o n by th e tr o u s e r s and o v e r a lls a ls o help s th e p ro c e s s. I t la in te re s tin g to note th a t no tro u b le of t h is s o r t was ao tio ed ia i Sagland u n t i l m inoral o i l roplaood anim al and v eg e tab le o i l s as e j v m ^ l lubrioant . Henry estim a te s th a t 0.20* o f a l l ootton anile spinners in Xnglaad s u f f e r from s e r o t a l o an o er. On the o th e r hand in th a U nited S ta te s during 1984, f o r s a m p le , th e re were only 88 deatha from oanoer of the scrotum , of vhioh only th ree of the viotim e mmT* t e x t i l e w orkers and th re e were mule epinm ers; fo u r o f th e s ix j ere born in England and the o th e r two in Canada *8 , whioh tends to show t h a t mule pinner oanoer la r a r e ly c o n tra c te d i a th e U nited S ta te s . ^ woolen a l l l in th e United S ta te s employing about 800 mule no 0 of norottX o .n o .r m . fo u n i <*. s lll. . , h. M th04 of o p e re tlo . t h l . o ^ lp w n t 1. t s . n n l,, both o o u n trlo . th is o t r l i " * 0 a tr8 S t i J *t tr lb u to d bjr n o a lito a 40 to t k . fo o t th o t ^ o t t l . h *M i* o i l la uood l a th e U n o o o h lro 111, . E oooror, the U to r o tu r o it not e n t i r e l y o le o r aa to th a o r lo ln end %pe of the o i l n ee d la Lanoajhire in male pinning 70 Leitch brings out a foot of poeaible significance, to t * e f f e o t th a t oanoar i . not known in woolen a n ln n lM m n T. ttiougb the sana m aehlnes a re used a s in tb s o tto f a c t o r i e s , but points o u t t h a t tb a roon te m p eratu res in tb a o o tto n n i l l s a ra mioh bighor, possibly re s u ltin g in aura re la x a tio n of tba tlssu a s of tba sorotun and p erm ittin g en try of o i l in to tb s sabaoaous f o l l i o l a s . Brookbenk , however, s ta ta s th a t in tb a woolen in d u s try p iao in g of broken nds of yapn is dons w ith both bands w ith a forward le v a l bending o v e .e n t of tb a body and th u s t b s r s is n o t tb s Sana f r i c t i o n of tba o lo th e a on th a s o ro to a as in tb s c o tto n n i l l s . Ha a d n i ts , however, th a t tba sana o i l i s usad in both typos of n i l l s . As a r e s u l t of tb s p re lim in a ry in v e s tig a tio n o f Southan and v.iison m entioned above, tb a M anchester Canoer Commiesion, con s is tin g of nor# th a n f i f t y n e a b e rs, waa organimad in 19t s under tb a d irection of Dr, c . C. Twort to in v e s tig a te th e n in e r a l o i l s ueed in M anchester o o tto n n i l l s . L u b ric a tin g o i l . from th e v a rio u s f i e l d s throughout tb s world wore found to have w idely varying d eg ress of a o tiv ity . A aanpla of Yononuela o il was very p o te n t w hile Hnaalaa ad vspj gfl sam ples were on on average l a s s th o n e -te n th as activ e. P u rifie d aS & o ln U o i j had no oarcinogenio p ro p e rtie s and a v e ra l ?ftP9ftj f l afrl f 9l l t . such as s p a m , o liv e , ro p e , oottonseed nd a e a ts fo o t o i l , f a i l e d to produoe tumora whan a p p lie d to a lo e , 7 f ven under th e most sev ere ex p erim en tal o o n d itio a e . i n g e n e ra l l i r e i , the more ea tu rn ted e re the e o a s titu e n t hydxooarbwna of th# lubr lo ttin g o i l , the le e e oapable ere t h e / of indue in Oftnoer in ex p erim en tal an im als, th e pfeysioal o h a r a o te r le tlo e being th e ssrne x . This p relim in ary re p o rt as o r itio ls e d seveM y in an d lta r ia l in the "Petroleum Times" of London * in th a t w hile various o i l oompanies ( A nglo-A aarioan, :*nglo-Praian and 3fcellgax) had c o n trib u te d 1,000 f o r two y ears f o r th e su p p o rt of th is in v e s tig a tio n , y e t the Menoheeter Saaoer Commieeion had not availed I ts e l f of the eervioee tad advioe of expert from the o il industry r e la tiv e to the o h e ra o te rie tio e end methode of t r e a t ment of petroleum o i l s . I t s I n s t i t u t e o f P etroleum T ech n o lo g ists, b ile making no d e f in ite e ritlo ia m e a t t h i s tim e of th e work of the o o m laeio n , formed a oommittee o f i t e on to fo llo w oldeely tha ork in p ro g ro ss W . In 1934 Dr. A. X. Duneta n , Dr. 7 . H. S erner and k r . James Kewley of th e I n s t i t u t e of Petroleum T ech n o lo g ists are shown as members of th e U aaohester Coemission 81 In 1933, Twort and Lyth 104 o f th e U en eh sster Sensor Committee re p o rte d th a t by means of s o lv e n ts , e n t r u s t s wore obtained of high r e f r e o tiv lty and correspondingly high oaroinoganioity. Their raoonmendations fo r the ee leo tlo n of an o il of low o a ro in o g e n io ity e ra ae fo llo w s: '\hn s e le c tin g from se v e ra l m ineral o ila w ith sim ila r g ra v ity , ep eo ify t h a t w ith th e low eet r e f r a c t i v e in d ex ; when se leo tin g from those w ith sim ila r re fra c tiv e index, epeoify that; lth the h ig h e s t g ra v ity ; hen se le o tin g from those w ith sim ila r r u fra o tlv ity , sp aeify th a t w ith the h ig h est v is c o s ity ; and hen gflotlag fro o rig in alono, ohoooe in tho follow ing o rdori gassian, Pennsylvanian, Tazas, x id co atin aat, koxioaa, C alifornian, Persian, P.ucania, Borneo, Tonozuols^ alalo. However, i t ahould bo emphasized a t t h i s p o in t th a t tbosa authors s ta te d e f in ite ly th s t "adequate rofln< a of any of tho o ils haadlod, of no n a t t e r what o r ig in , r o a u lta in a produot ......................... only a very low o aro in o g en lo lty " 104. M ao, that a ainalo o ztrao tio n of an unroflnod d ia tilla to with 80, nay profoundly lowor tho a o tlv ity of a p rev io u sly Tory dangerous o i l , hila a aooond o z tr a o tio n nay ro n d ar i t a la o a t i n a r t . Thoy a ta to that " i t la probably ooauM roially fo aalb lo to tr o a t o ila of any origin, or o lla of any dagrao of oaroinogonlo a c tiv ity , so th a t thoy nay bo lo a a dangoroua th a n o ran tho Tory b o at of th o a t r a l g h t o lla used to d a y " . Thoy o T ld o n tly aaauao th a t u n tro a to d t o z t i l o o lla aro asod in tho Lanoaahiro n i l l a . Lyth of tho S oaniaalqn f u r th e r s ta te d 71 th a t when tho re frs o t l v l t y * of an o i l woo lo a s th a n 0.3&00 i t was found to bo non to z io , h ilo ben th e value was g r e a te r thn 0.5000, tho o i l wan highly to z io . Ponnaylvaninn o lla and c e rta in m ildly tre a te d o lla were an oxo o p tio n . The lo a in o f an o i l soama to a ffo rd an indloatlon of lta to x lo lty , providing the o il has not been treated and a g a in th e h ig h er th e v a lu e , th e a o re p o te n t th e o i l . The to x lo lty ln o reaaea in th e earns o rd er aa io d in e v a lu e , sxpept f o r Peanaylvanian o i l s whloh ag a in eeeapy to o high a p o a l tle a . The pom angan ato v alu es a r e n e t reg ard ed a t of any v al a in ooanootioa with a a tin a tln g tho to x lo lty of o lio . *(K fraotivityS 1 ) I .ujfcn Bflu< th a t e x tr a c t*io n w ith a lc o h o l , oetone, t o ., c l> aau a o iJ tre a tm e n t, lead to * re u a c tio n in iha potanoy, *9. p ac ia ily in th e oas* of the more p o te n t o il but m co rresponding reduotlon in the r e f r a c tiv i ty doe no t alwaya occur here a narked reduction in the r e f r a c tiv ity doe ooour, th e re i , w ithout exception, a narked deoreaae la oaroinogenioity; w ith a narked iaareae in re - f r a e t i v i t y , a co rresponding ia o ra a a e l a potenoy. 7,h ere th e r e fra c t lv ity ia not nuch a lte r e d , th e poteney nay or nay aot be affeo ted and f u rth e r t e s t a a re neoessaxy type. Ia p ite of the eppareat d e f in ite finding and reoonnendatio n a o the M anchester Canoer C oanlselon, th e Canear R esearch Conn i t t e e of th e I n s t i t u t e ot P etrolefcn^T eehnoloalete 81 was ao t oonvlnoed th a t "th e s o - c a lle d in o ld eaoe of oaaoer i s in any sh&pe or f o r a connected * ith the uae of a p i a d e o lla " . So e la b o ra tio n of th is a ta te n a n t wee g iv en , but was p o ssib ly basad on r s f ln e d o i l s only being used as te x tile lu b rlo an ta. An e d i t o r i a l in the " P e tro le u a Tinea" o f London in 1937 onoe again attack ed the oonelualons of the Hanoheeter C p a alttee , pointing out th a t only one o il fro n eaoh of e nunber of eountrlee was e x e n in e c . - 10 In 1937 th e F ed eratio n of M aster O otton S pinners ooiation sent o at l e t t e r to l i e neafcere reoounendlng th a t ^jjfO purohasing sp in d le o i l s a g u aran tee should be obtain ed g,st the o il confom a to the ap e cifio a tio n s of th e Manoheater Caaeer Conail sa lo n , and th a t te e te bad ah earn th a t nany of th e oils la use a t th a t tin e conformed to the s p e o lflc a tio n . While throughout th e rep o rted oork of th e Manchester Caaeer (gaaisaion i t la s ta te d rep eated ly th a t aold or solvent treatm ent of , potent o i l g r e a tly re duoe a or e l in in a te a i t s a o t i v l t y 99 109* *1, y e t in 1939 T eo rt and Lyth in v estig ated aeid and slay tre a te d d i s t i l l a t e s from a Bourne e l l and found th e n to bo a o tlv o , tho a a x i- - * - - . -- gm potoney being a t a v ls e e d ity o f 100-380 op a t 180. M olecular d is tilla tio n gave a g reater_ eo n een tru tio n of tho oaroonogonla n a te r ia l t_ha-n was -- obtained ~ by ordinary d istillatio n a t fren 3 - 1 0 *. a--n-.- In o iflrn atlo n of previous findings ths niddls fractio n s of th is Borneo o i l wore n e a tly re s p o n s ib le f o r p a th o lo g ic a l changes in tbs organs* a oarelnogenle shale o i l was separated by n o le e u la r d i s tilla tio n in to fra c tio n s uhleh were subjected te abronatographis adsorption* Two a p p a re n tly pure hydrocarbons have been is o la te d and are being investigated A re c e n t r e p o r t (1941) by 0 . 0* T eo rt of tb s K aash aster Caneer Conmlssion 109 s ta te s th a t f t a are v ariab le. lsngthy and a o s tly and t h a t a more r e l i a b l e e a tln a te o f th o e a re in s g a n le lty of o ils oaa bo obtained fro n tho ro fra o tlv o index and v iso o a lty . (Tet th e d a ta on e h le h s e l e c t io n o f thooo boo p r o p e r tie s was baaed a rt obtained by naans of th is v a ria b le ak in t o s t . ) Woodhouss of th s Blsmiaghau Cancer B asearch L aboratory also sta te s th a t nouae te s ts to dotom ino saroinoganiaity are d if f ic u lt -1 1 - I %0 c o rre la te with human te n d eao ias to oanoer u n le s s th ese anim al M fta ara s tro n g ly p o s itiv e or n eg n tiv e 121 * f o r example. two o i l s *er* ta ata d (a) from a apinninc: n l l l where no oaaes of male sp in n e rs 0^ioar had bean reco rd ed , and (b) from a m ill whera s ix oanoera bid recen tly been re p o rte d . house ta a ta lad lo ated a lig h t oerolaogenla p roperties i n th e oeee of th e two o ila but a g r e a te r a c tio n on mioe 0f (a} than (b) . Dr. X. M. Brookbenk, ohairman o f the M anchester Cancer Ccamiaein . h*a b r ie f ly sunnarixed th e in v e s tig a tio n s of th e Coaoiaeiom ia re e e n t p u b lio a tio n 1 6 . Ha l i a t a th e h y g ie n ic p re c a u tio n s to be axeroiaad in mule sp inning and urg es th e adoption of th e o i l s p e o lf i- oatioe given p re v io u sly by Twort. He a ls o makes t h i s in te r e s ti n g n a ra liz n ti on: "As a g e n e ra l r u le an o i l th a t la s tro n g ly d a m a t l t l a i l l not be stro n g ly earolnoganlo and vioa v e rs a " . This la alao n titio n ed by Kannnsmy 61 who a te te a t h a t ayolohexena (which is ncm- earelaoganlo) is axtram aly ir r i ta t in g to the akin and should pro- daoa oanoar i f ohronio l t r l t a t l o m ware an a a a a n tla l f so to r i n o a ro in o gansals. | Aa m entioned p re v io u s ly , ih a la o i l s a re a e ry oero in o g sulo and in th e S o n ttia h sh a le in d u s try the oese in cid en ce o f sk in oanoer la about 0 . 1% per annum among th e e l l w orkers b u t 0 . 8% >{ th e p a ra ffin w orkers M ( t h i s is baaed on a 8 y ear r e c o r d ) . Tfcie a c tiv ity of p a ra ffin is r e s tr ic te d by Schwera and Tulipon to the crude p ro d u o t, th e r fin e d wax being in a c tiv e , whloh view i a supported by Wood who s t a t e s th a t th e a o tiv e components a r e p re s e n t only la the crude p araffin o ils . w ith re g a rd t o th e r e f in in g o f petroleum o i l s . Wood 120 ade an I n v e s tig a tio n o f r e f i n e r i e s in Pennsylvania and found no o ro to l o an o er, whloh waa confirm ed by H e lle r However, H eller -IS ***** idea o f oaroinogenio compounds in M id-C ontinent o il a r ,fin # d in p la n t in Ohio and In d ian a . Hero o i l b o il aro f a i r l y on and in some o a so . lo ad to kin oanoor. In on o a s . a j a r i f . nn-- p rlaanan in th Middlo Woat was tro a to d f o r "wax bo il f o r thr 7 ara when a oanooroua growth dosolopod on tho r i g h t foroarm *ad was romosod, but o ig h t y ea rs l a t o r a ooad s im ila r growth in tb# amo plaoo had to bo romosod. H o lla r a l o found ro o o rd . o f of akin oanoor in an othor r e f in e r y , u sin g orudo from tho fio ld ; ight oases had ooourrod in t h i s r e f in e r y and one waa f a t a l . A ll of the oaneers were preceded by w a rta . The le n g th o f exposure before mallgnanoy appeared sa rie d from four to th ir ty four y eara. The p a r t most o fte n a ffe o te d was the aerotum and a l l b u t one man worked in th e p a r a f f in d epartm ent. These eases wore oaused by un- rt I n_e<L ? H a and H a m i l t o n s t a t e s th a t ao f a r th e re is no p ro o f of th e occurrence of ak in oanoer in th e V*S. from th e use of r e fined lu b r ic a tin g and a p ln d le o i l s which have been a o id - tr e a te d . H eller bellew es th a t the r e la tiv e freedom from occu I p a tio n al oanoer in th e U .S. i s due to th e m ech an izatio n o f i n d u s t r i a l processes, p resen tin g d ire c t oontaot w ith the pito h and bar; the e rta n s is e employment o f n eg ro ea, who a re a p p a re n tly le a a su b je o t to akin i r r i t e n t e than w hitea; the use of re fin e d lu b rie a n ts from crudes whieh a re peer in eerelnogenlo p ro p e rtie s , and the use of ta r from eoke--osens in s te a d of from gaa w orks. P h illip s ^ rep o rts the p artic u lars of a study oarrisd out by the U. 3 . P u b lie H ealth S e rs ic e >aa to th e in eld en o e of oeeu- P atlo n al can cer in Texas. The re c o rd s of 1190 ln d is ld u a ls basing nioroaaopieally w erifled skin canoera were analyzed, ooserlnr, the Period 1930 to 1940. The ooeupation of th e la r g e s t group of th ese -13 p a tie n ts was outdoor work (farm ing sad ra n c h in g ); th e work of poueewifee oomaa n ax t in o rd e r, follow ad by v ario u s a e t i v i t i s s re q u irin g modarata outdoor U fa * The p ro fa aalo n a v a ra n a x t, followad by la b o re rs and o a rp a n ta rs . The r a ilr o a d and petroleum in d u etriea fu rn ish ed faw cutaneous ca n ce ra . O afafar and sltg re a v e e in a U.S. Publio H ealth re p o rt i*ued in 1940 S7 an a ly se 70 e a se s of ean aar reoorded f o r th e mala weaker of th e elo k b a n a f it p la n o f an o il anpany during the p e rio d 1933h36; th e re ware 46 d e a th s . The d ea th r a t a was 0.76 par 1000 and a frequency o f l .S p ar 1000 ( a l l U .S. death r a ta 0.96 p ar 1000) Almost 70% o f th e d ea th s ware r e l a t e d to th e digestive system and th e r a ta fo r th ia a i ta was higher than in the u h l population. Deaths from eanaar of the g an lto -u rin a ry system see t,9% of th e t o t a l , eoapared to 16.0$ in the ease of th e t o t a l papulation. In 1934 Canpbell ** nada la b o ra to ry ta a ta on miea with duet obtained from ta rre d raad n . This duet caused w arts and oaneer o f th e ak in and in a ix months 64 o u t o f 69 n io e showed tTpieal ta r w arta, h a lf of whiah developed malignanoy. This flailin g was confirm ed by X lln g , aeneonow and B eroe, 66 who a la o sp p arated a substance oo n tain in g the bensopyrene naeleus from th e t e r . However, Hogouneg 47 i a d o u b tfu l o f th e danger from road t a r ein ca i t usually takas years of d irso t ooatast of so al ta r to the akin to produce akin cancer. (T eutsehlaender c a lls s tte n tio n to th* fact th a t almost a l l In d u stria l oaoeers require an exposure of about te a y e a rs b efo re growth a p p e a rs, alth o u g h a fsw e a sa s may a r i s e anoh l a t e r ) . Y alade 111 lik e w ise i s o f th e opiniom t h a t w hile p r l - aary lung tm w n can be induoad in mice p ain ted w ith te r or exposed -14- to in h a la tio n of d u at f ro a t a r ro ad a, y e t th a t a r a a u lta oannot ba tran a fe r**4 * kUMana. n ia a la o th e r th a n a lo e ahould ba aaployed in ax p ariaan ta and an in q u iry ahould ba o a rrla d out on workere ax poaed d a ily to auoh d u a ta . Wbila tha M anufacture of b rio u a tta a in Xngland ia attandad by * bigb oan e a r r a t a , 88 a ln a a h lg h -ta a p e ra tu ro t a r ia uaad, jrat in the fa a p lan t* in th a U .3. Making b riq u a tta a oanaar la a n tir a ly ibaent, p a rtly dua to tha laak o f o ontaat w ith tha binder alnoa tha prooeaa bar la a n tir a ly naehanizad and p a rtly dua to tha uaa of p ttro leu n a a p h a lt aa a b in d e r, 88 Thia fin d in g vaa oonflm ed by vood in hia in v e stig a tio n of b riq u e tte manufacture in Pennsylvania. Iha a d d itio n o f g ly o a rld a a 89 radueaa th a oarolnogenlo potenoy of m inaral o ila but n o t to aa g re a t an e x ta n t aa ggo^jg. ipeakaan and Cham berlain 89 a t a t a th a t a h lla a le o h o la bar*not bean uaad f o r th ia purpoae th e r e aan ba l i t t l e doubt th a t auoh p o la r ooupounda w i l l re tu o e th a r i a k o f oaaoer f o r n a tio n by p ro a tin g u u la lfio a tio n , ainoo an o i l whioh la a a a lly oom plately ranorad froa tha akin m ist c a rry la a a r ia k than ona which ia d if f lo u lt to w u la ify . Tha*a in v e stig a to r* alao b a lla ta th a t p o lo r eonpound* in n ix tu ra w ith M inaral o i l nay, however, fu n e tia a in y et another way. I t la known th a t th a o arain o g an lo agan ta o f M ineral o i l * ie n a a so o la ta d with u n aatu ratad ooupounda era fro a to ooneontrato a t any aurfaoa to *iioh tha o il la ap p lied , the noa-polar p a r a f f la nolaaulaa o ffe riag l i t t l a a r no r a a ia ta n o o . However, whan o il- a o lu b lo p o la r oompounda, auah aa o la y l alao h o l or w o o l-fat a th a r, a ra Mixed with Mineral o il thay aonoantrata a t th a aurfaoa, axoluding tha laaa polar oaroinogaaie hydrooarbona -1 5 .,u .lr r a tr a .... tb. ,, ,, ,, U y ar rtl0 lu t< 0f body d c lo th in , tho . p p i m t l o n o f w t t o r a l l 5 to anpooid ourfi ~ - l t l . . t i o n . T tr7 th r . . KJnth. < p ro iib M k l5 ' I l l t u r * of i a a u . . - t u m oU . w l l .d to tb . ..V h tdTOOat. t h . . . o f a U . ,, l m t a l ( m ,, r , 1^ 1 to t h . . t h . r u ..d U h o .o lt.1. ln o rd .r to r o T . , u of tb* lu b r ic a n t f r : * tb* 3o r* * 3 , In nn of th . *u*at,d of lanolin th . fo llo ,!. Oonld b . Of p a r t i ! . , l . t . r , . ,, Dr, . T. C * m . o f t h . ..hln*ton O n ir .r.lty sohool o f .d m ., s t . t a l l i J<ljt aanoua..d ( . , Harald T ribun. A pril 19A5 t h a t . . U . . , .ltl l to . . . cana.r u , b , tr.a tln * t h . tth , N b ||n |f loh do., not . . . . and hlah will ,, m ?r,, m t u .w p ro d u .la i M o t H fro arh lb ttln g th a t prhparty. for .ia .p l., a * h. p m m ..,, I n o * . ..th y lr to l.th r . U a lx ^ lth la n o lin I t la lthout a a t l h u a p p u n t a th . hin . f * . although , 1 . . l t a l waya r . a u l t . U a,, ,, ,, ( ^ th ... I o . t h tr a d with . t h y m o l . a . 1 , . . . . . ^ d .lo p l s . a . . r . aon <ra!tlf and t a . r o o f am atar r l r l l l t y than 1. . h i. had o t I n i t * . w a a . p r m . t l n * t m ( WTl DVS  . -IfRFAR.MICZg 1. Anon., Caneer fro a Spindle O il. o i l and Color Tradaa 7 . . Xfely 2, 1937, 38. 9 A la tte r cent out b j the General Comrlttee of the Federation of Msater Cotton Spinner** A ssociation reooenends th a t when p u rch asin g a n in d ie o i l aen b ers should obtain a guarantee th a t th e o il conforms to a s p e c ific a tio n o f th e H aneheater Cancer Committee which rece n tly issued a formula elalned to minimis# the so- called oaneer-produelng eleaients of n in e ra l o il. Teats showed th a t many o f th e o i l s in u se a t p re s e n t conform to th is s p e c ific a tio n and a re obtained a t re g u la r p rlo e s . 2. Anon*. Cancer and M ineral O ils* O il and Color Trades 7 . , 102. 695 (1942) The report vojf twhe M--aiinacuhcees^tecr CMeawmniteteee on Cancer. i Issued fo r th e 1F-e--a-r-"enJdJed Octob--er, 1--9--4-1. s t a te s th at in e f f o r t s to I s o la te and ch a ra cterise ln d lrld a n l carcinogenic hydrocarbons from sh ale o i l , recen tly appreciable quantities o f sr y sta llln e material bare beam ob tain ed , but i t I s to e ea rly t e d iscu ss r e s u lts i s d e t a il. As fa r as asm be Judged, e l l fraetlom e * obtained from Tsnesnelen O il by chromatographic ad* sorption are aetlT c. Froprlstary oolloid s here earyiug e f f e o t a , depending an the con d ition s o f th e experiment. A c o llo id containing e ehlor-eompound one foaad le e e e ffle e e io u a then an o l l r e o ll* la n o llm e Mixture as protection against the earelnogsnls eetian of shale o i l , fells the rererse appeared to be the ease Oban th e csroln egan le agent used wee bennpyrene. 3. Anon., The Froblen o f Cancer. Petroleum Times, 23. 99, >X> (1930) (e) The fe lle w in g appeared la a re ee et laana o f th e B r itis h Medical Journal in eoatncation with th e t i e at mlnornl lu b ricatin g o i l s in the lamocahire cotton m lllst "The Manch eater Onmeer Ccnm ittee, c h ile etndyiag the pert played la the produetle a o f Malignant growths hy the lnbrleetlm g o i l s need in cotton m ills , has obtained inform ation about th e ea reln o g a n etle power o f wnrlone o l i o and th e eonaantratlon w ithin them o f a cancer psodnelsg p r in c ip le . Za th e course o f t h is research , two pare compounds at knoen ehsmleal sem p ssltlen ham bean prowed capable o f producing tumors, and e study has bean made of th e fa c to r s which change e tos-eeiu lib ogenle la t e am e e t l m eereln ogen le eubstanee. Already -19- 0 * th e m ethods f o r i e a t r e 1zut th 9= .r c f c e r t a i n o i l . h ,t . c r o i . f J be t\:ra\ZV^ im a o n with th crude u n treated a i l h>vi ++ ? C oom^mnittet ien f1?thwe re fio*r " aiib>l>e "toS ihro.lsds otuSt th e hooa th a t u * if oi i l 0w! ?hio1h? " !f*u,1l 4f i.*l * 7 t b# ha naada of to put on th a m arket an industry without being a ajuroe of danger to tha workers." ^ Assuming th a t th a uaa o f sp in d le o i l s bs sush a sourea rlly follows th a t other "h 1011 ** i* to c lo s e r p h y sic a l o o n taet with the worker m a t bs souraas o f higher p o ten tial 2h S * ? TM hai\.*?w l i *h t lu b ric a tin g o ils used in hi f th ? *" ?**** Otton I n d u s try . I t n ig h t be proved uoon In v sa tig a tio a th a t l i t t l e d if f i c u lt ie s thansalvas In the production of a spIndia S! ' S e e .lS 1!? 1* ad l a s t th a p rasan t a tta c k widens l t a a l f to in slu d a th a whole ranee o f m laam i i.b rt ti , o n ., u id . .d r t ..b T .i o ^ ; v sstlg stlo n o f the most enbraelng ch a ra ata r. Anon^j A Dengaroue R eport on L a b ria a n ts and C aaaar. P at T ins*, 22, 319*320 (1932) wanaar. P at. C ritic !ts a tha rep o rt of the Banehester Canaar ^ th a t th a Committee has aeoapted a o a trl* S ^ r V V 10?0 f r tW 7 # t r i fTfm thP^Jnglo-A m erican. l t I a i ? i i r r i r , l a L ? nd th# a # n ** *t has not a v a il* *?*'* * sdtrlsa o f s z p e rts from th a ^ d u s tr y r a l s t i r a to th a a h a ra s ts r end Methods of treatn sn t of patrolsnn o ils . AUOni i , l^ 5 h ( l i 3 7 l CaeiBlttee * Cmn*T H**o r t * T in a s, The 1935-36 r e p o r t o f th a M anchester Committa a on Cancar a la in a th a t "w ith a kaowladge o f th a re fra c tiv e lndaz o f an o i l , and o f th a w laao sity , ona ean fo m r e l i a b l e e s tim a te o f i t a can car-p ro d u eln g power * then by tha ap p licatio n o f tha sanpla to tha sk in ." *h how iT,r th a t s im ila r so aslu sio n la 1933-3A r e p o r t was baasd on i n s n f f i s i s n t a rld e n a a and th a t sons iis s rs p a n o ia s w ith animal t e s t s wars a d m itte d , agd th a t in th a 193A-1935 re p o rt th a animal ta a ta were rm rarted to . I t la alaa painted out th a t tha above conclusion was bassd on tb s sx a n ln a tio n o f o n ly on# o i l o f a number o f c o u n trie s. ' Ib" *?2" a ^ ^ iM rcaad lo w H1 s .*StTh * * ? ' " *r t3tt osl ls. Th ok p la n t . ^ P e rio d i1 x ao ln atlo n ln 7* r i r a Ala?JH%?VCaaf t r ; Msrb1y1'PHr7lalrKo*ln*i^rya*T-rtant d0*#* * i 1* ? " 1" " * " d 1 *? * 5 , 6 ^ i b S * S t h i . grasira- r& r^ S S L S ^ S S S S S sS S ^ f - S S s ^ lonally IJO^lBOydH, w f O ^ U { S f " 1 p la n ta tio n o f tfco _____ " a liT r# .* * 7*^?**0** ** * o t " . i y . M A ^ ** *, t i T * Bachaann, . X. t a l . fro d u o tlo a o f ta n n o r w 9* ~ srra ^ S L S m STLfr? i?asjB SS a:, b.%"- ^ . `^ ^ r ^ S p ,yr4^ -If- Proo. r j P Pa r t H jd ro o ro o n .. " <- ro r U . " 4 wallowing oeanot lB* * l tio n Th* 3 ,4 -b e n z o p h e a a n th ra ie Zm 1 a T " 7 tfc* . bparnozpaenrtthi eraao, cnaanad inp otka ram-tJly; . * 1? , ffor* i*!itflv! e, , *thwaBnr tihnao**a l * Oholangiotta. end *l*l*i* tunora, ooapounda apa m o r e ^ c t l r ^ w i t h i W I - J hi 1 ** e t i t i tad Compound a a u b s m u t e d o i t S J * * " ? *" . earelnogenio than thoa2 a n b 'tU u tS Uf * ^ I 7 ro r # Aaong th a 1 ,2 -b a n z a n th p a n ia a a !? ?* J 7' 8- " * <. - m p i . 1 2 . ^ j v s s s r . p a ,i i T ,, : ^ ,, u o n . Mihfliiillflii SimSTSSS' & & ,, ! f 2`J p o a itio n ? f and*" to lli tf? i ! S a n th r ! n* ' "^ t l t u t l o n oarclnogcnic a c tio n : a o a t'o ^ th M * V ji po#J tlo n L r ! "" In 1# oronoted h V r r i ^ y br u ^ % ^ ^ w - sr* tumor? could n o t be aseri>*rf -i* v ^bU e m ultiple o f the BdEiniatfrred eomuiinda of c u ltlp lic itv oocurred *?! th * aotloB 8 trlk ilis cnsea pubrtltuted o h e n ,n ? h " ,t l ,? - 5 , 6 - d i b e n z r Cr i d i n i " ' l" ?J * 56- d i t * ff azocarb:.z r . 1>*V,n"d P ro c . ^ y I 't S o c f" l l 7 ? At l g 2 o C(?Q ?c)by P u r* ^ ^ r o c a r b o n e . p a n t a i i 2 i i BS S ; i t i i h U f l y t e t r a c y c l i c ^nd -20- 12* A gents. r te a o r p ro d o itla n br f t c t l r l t y , Xrtrr uhat,^*_5 ?*'50ua^* d a ta n rin a i t a o lo a tly a g ira n * p a ra n t" s t o t u ! ^ B tt mora o r l a s s i t * b l s a t o L t o s " t r ? " F 8! ? 1" " lao U th s o aro ln jg sn a a r t adsorbed kw *^a l i rin g s a l i , ` i i f l n l t * a d so rp tio n a r a a ^ h i ! B- * * p to r P o i M u l o | f o r th s d ia s a s io n s o f J a fS 88t8 an B 1W l i n t 11*1t la I r by . J * ! \ l7 # pounds. A lo sa r atending t u It 2 . " u * r i l l *r r 1" ra eoaoalrad as parta o f a ? J * * i ** **} oaralnogana 1 . A oarclnogan o u ha l a m i n a d h ^ a " 1* tru itu **-' p r a r a n t i t a p ro p ar a d a o ro tl . i 7 d<} tl0 M U f irn 1. S ": #f m . 13. BOn" i. * L ; .I X " 7 7 U h( l |$ 12 * " *. obt* * * with four s a la la , m m - - - - tahs t ip S E r j B"M_ S 1"tho^ugh n4ot sa patant aa l a * for b u i* tin t th i n o r T i i n 1* " * " m z ? : *>* s u - i i S u i o ^ U i ; ? s s 2 r U * . b liir U hand aal o r ta r s , and U o sa A a a l l ^ ^ t E ^ l f i E N f c f c I t " ! 1 rt S S i 1 J ! | * i y g ` Alaaaaa. naphthylaslnaa ara Sara f!tt* f ^ y ^*3 * " s r ^ H s S i & y S a ^ r t u t u f t r V ^ L , f f J * * " " > i U mo | la istto . inte s s m r s : Ba or * d i as la rata hj a' snapa u la * a f - - ---- M W IM U o m it n i > * * a la s p h tk j] !?sr lajoatlaaa a f a 1. Brookbenic, . m. (4.36.41) Mula-Spianar* Canear. B r l t . Mad. J, 6t-3 l d . a . 3* pp. ( m ) ' ***?" - >< K- t wl " **. flr tt koom eaai t aere ta l , aplanar as reportad in Maaehaatar ln 1687. 37 reara Eo i rfo rEt tsh a^ t Sti n0a* t"pe"n1 o l * alnn#d rfstul tliuf bo rolot aotllag haod lk ^m tthha. op ruin,c ip*a.l tltn. brr;i?e an tIs . I it tla S I S ' w? ? 4 of p ia str a i i cansad bjr oaroinoganle ooaponnds hloh ara presan t la a ln a ra l ln b rla a tln g o i l s thonah a o t la luhri J K L f S a 4. ! * - u rl- daS ? I tkaa o th sr s, tfaat J I 1! d rf * * ^ 4 balag p a r tla n la r ly daagareua. | * to b ^ 1? ^ arparan t t i t u t S U M i S l i k i W ah ?. -i*f kIS?f k i i J !JT! * p lo r a d la 11o s s a s lo n a lly atna i. fw a th at br aixiaft H M i r ^ r r : l n b r la a a tnni naye rbsel aobl a tathda. o a rs la a c a n ls p o ta a r f T|t a uaroiasgaasslsi X^th.a* 5BfrfKoTst ^a f! tha*B e*bantaXnsparlamants la S tt?2T I*otlon a f Lord, O llra 611 and tth ar A. Ikparlaaatal rodnstlaa a f Can w m " .f h" .* ? '" (m ta lM ik ! S " 2 I 2 E S ? *" 1" 1 * " 1. 4y bansaaa sas aot sansa soasar a f tha tfeSa **# i " btlaalataa tha paadnstloa a f l a i t o n la n laa, bnt aat ta aa graat astaat as shan tha tar la >. Caapbell, J . A. Carelasganla Aguata rasat la tha 1 Zasldaasa a f.lr ia u jr Tnaai la rit. / . P a th .t ltt-s a U vrll 1 9 ) fita nabar has aatina ai h la -SS- fro* x h au ,t ?iP o f c i n ta burnir* -5~ L4hT*- 9*-3V"2 Si"ii! jiri2^a*** ** H W ithin t h . l i m i t . et t e n t ~S s~= ~i 5TJSW JSrJi 5 j P " ? s . ' . ^ s r t i ^ . '^ n s . \ r ; 5 "mi.!a:..srasrLu9^l,*tlJ,*ou* - e ! m .4 .. ss. eook, / . W., B avatt, C. and I I car, I* Coal-Tar Conati t a n t a and Cantar. Vatnra, ISO. t f (l i s i ) * 1W* ' * W M i o la ta d f r m t o i l ta r uhi ah ja ra a o tir a In produalac onaara and adii ah had tha ty v le a l naoraaaanea apaotrm o f aaralnocania fr a e tlo a a . Tha oat a t t ir a hydraoarbm la o la ta d v ia l.t-h a n sa a rra n a ahi ah i* i!? 2 r d,5-banaopyrana vara ala C*k , i i i f f 11, ^ lydraaarbooa. f? f y * 80 (londan), B ill. 458-94 J ltM h * ^ 2 * *T* * _ i14), J 2 J , d 8 5 -td u(lSiSS)i * ) le * ad aa n y U . m in a la , and a atady v ia nada a f tha aotion a f SS d iffa r a n t p o ly a y a lia arava t i a I ? I ? xOB,,wooatd* w ** i l th a ir raap. n a ia . m A W l i d d i ^ a a l n . ta tha intaraaapular raglan, uaaally tv ia a vaakly. Of thaaa pura aanpda. on ly l,S ,5 ,$ -d ib m thraaana and to r ta la ila a a ly ralatad aanpda. praduaad em ta r; l t vaa a o tlra in d iffa r a n t aalran ta, and m a a f f i t t i r ahan appliad in O.OOfrf a a ln . in CB,. S f t?ll ina!?i UldfinNet 2TT api t h a ll ana, a* Pan<d` 8W1 p adpvirllaalnopaaad. tunora, a ! 5 L ? * hm* barn txtandad ta in alata 5S addai. p a lp a rti!! a rm a ti! aanpda. Tmora vara pso- duaad by^4-iiop rap yl-1, S-^nsanthraaana, 5,4-tyala-* b-bw ianttuaiana, phananthraaaanaphthana. m i S4. CMk, . V ., l a v a t t , 0 .1 . and i i ^ ( Canair -fr o d a ain e Kydra 8o a ., M 5-405 (19SS) Z. Tha I t a la t i ai a f O tti Tar. i; Tha praparatlana darirad fran aoal ta r p lta h br a ra ria tj o f aalrm t artraitian natoda, tha fr u ttim i aaparatad by fo r m a ti o f p if r a t t a , d i s t i l l a t i and arja t a l l i s a t ir a , and tha hydroaarbm n.li ` ' and 4 i5 -b m sp y rm a , parylm a and l,B -ia n bara prorad a a ra ln a c m li and bara Iran tha am a a m a i apaatrm (banda a t 4000, 4190 and 4400A ) . orinlnal a m i tar pitah amtainad not laaa a f l,S-banmpyrma. I .i Coolt' **** M< B iologica! I ffa o ts o f Carcinoaonia H7dS ! i P?n! - t t * * " * * * . . W | 1016-3 (1933) # 4. <- forV 07 B* to occupatian causas 2 " ? *** o i l o d t a r ami lu b r ic a tln g I h S S 2 pl07#dl 5 l * h 0 m ahom * ba dua to tha bcnmanfJ11 f hydrosarboua A i s h c ia o inpart flu o rea - obcc to tha o l l a . Sha azaat natura o f canaar f o n e t i c a f *4y i u l Bot Baca enplainad d th ough a s im ila r bensanthraosne hydroearboa has baco fouad to ba produoed by body changas fron subataneas noxnally presan t la tha hunan body. I l , Ceok, J . W. C arsinogcnlo ly d ro sa rb o n s and f h s l r la la tlo n a h lp to tha B ta ro ls . Ghsn. Vaakblad, U , 968-6 (19M) 1 IcTiaw o f h is t o r ia d dsralopuant o f reeognltlan o f tha sanoar-proiuelni c o n stitsa n ta o f c o t i t e r and a a r lla r lnrastlgatlou s} tha l a r a l c p s t o f flaarasesn spaatre- saopy and tha sy a tsn a tla atudy o f sy n th a tla aralnegcnla hydrosarboaa Includine a tamii17 o f tha r o m it e obtalnad # f aa*Piata s c r ia s a f t e t r a - ani p cu ta cy elle hydraaarbons and a nadarat a ly a l i a ranca f bcnxanthracana do ri ra t ir a s . fha sp eculatlan la adranaai JBst naao K tto a In a ooapistaly aranetl a atruatura S S -F ? V II t y tlM << ilt f f a m . tha inaila- - tio n a f 1 , 8-bcnaopyrana fren acal ta r an i i t a aynthaolla * ara raaountai and an ao cean i la giran a f tha y e l i u t l a a * t ili. Mi I n l n U T H , . tki i ^ t L l I n S i i S r f ; !-- --1 . k j * --r t a a n U M u ths s tc r o ls . x t la in fe r r a i that thara la sona m ajal t t * w l M l Body A l ah la s a p a b le a f a ffa a tin g dshydrognailon a f Iha a ta ro l rin g syatan amA c e n tr i bata ta tha I * production ii*n rito a f" eXardmn aagaclrnalabU Ooak, 7 . T m _ _ _________ ___ w I L *lt-9i Ufi?) 1 f d l aurtai la giran a f tha eamlnoncnia A m ica la h ld iS a ^ 'l? N la n n h lp itd A lr **** hrlnglng together, Atar all -tr~Tu l ^ i i l ` H . " '* * 1" f u h llA a i up ta tha u n i a f ^ 7 tha h yiraaarbona n f tha bcnnanthruacna trp a , Vut a lc a tha ana aaupom ia, c a tr n , tha s ty r y l ^ulnalin a i T ira tira d iesa r arc i by t -- V i' f * } * 1* * Ina d e r d e md A btbllagraphy f 14 rufarmaao la sppmdad. Goak, f . I . n i l a u m r , 1 . L. O haulad fnnpnmds aa Caralnaganla n r s t 9*nlamm%*TT corti 11tartura a f 198?. in . * . Canaar, 96-69 (1986) n t w i U r * rarlanaf thla anbjaat y ^ f ^ d d ba af Interest to all industriai pqrelalaae. Zt continuas tha aarllar rarlan ani A a tua ranarta ta. i**** Bara blbllacraphlas totallag 994 refarcases. -2 4 19 rvi "* * Charnicel C ercin o g an aais. Drucs n** '* ''*T:* S la iio n in c iiia * `to U* l n t th * hody by in - r cSt , n *u* P P lie a tio n . He s tr o n g ly ^afnnvy ora cSl t. a2d?*auchH01a7s d e r"ir at ir e o f c o eaal rtceinr o. getrnuidc a M t . ? i l a * an a a l l i n dya "in te rm e d ia te * , azo dyaa and a a tro g a a io cu b stan c es. Tha a n ilin e b la d d e r tumor o f dya d*T alo? a a f t a r Xra o f azpoaura to what ara probably extremely n a i l d ally doaaa. *ha th e o ry la adranoed th a t th a ra aa y ba many o th e r carc in o g en ic aganta aa y a t unknown which a r a unknowing]r ln **! rovtia9 t ^ l l j U fa , and perhapa through th a uaa o f many drug*, p a te n t n a d la ln a a and c o n a tle a , r lta n in a , aex hormone, and th a tramandoua H a t of a n ilin dyaa uaad in tha coloring of food atu ffa ana fa b ric . SO. Downing, 7 . 0 . I n d u a tr la l D arnatoaaa. 7 . In d . H yg., 17, 138-168 (1935) A ra ria w w ith 208 r e f e r e n c e s , a s e c tio n on e h n i o a l ag an ta in c lu d in g in o rg an io compounds, hydrooarbona and orude co al t a r produeta and o th e r organio compounds: treatm en t and le g a l aapaota. p 1 31. f a l l , A. O il Button ( I la lo k o n lo a la ) . P ra a a a M a d ., 40. 1541-2 (1932) . . , . ? U CKlp i lo n V * * * in in d u a t r l a l workara eauaad by heary n in a r a l o l l a , in c lu d in g trea tm en t and prophylaxia. 32. f i a s a r , L. I . C arelnoganlo A e t l r i t y , S tr u c tu r e , and Chcnloal R e a c tlr lty o f P o ly n u cle ar Aromatic H ydrocarbons. " 1a*L An. 7 . C ancer, 34, 37-1*4 (1936) A long rariaw which include! I , a c r i t i c a l a ra lu a tio n and comparison o f th a aath o d a f o r d eterm in in g e a re in o ganic a o tir lty ; I I , inform ation oonaarnlng tha prepara tio n and p u r if ic a tio n and th a commercial aourcea o f th a c a rc in o g en ic hydrocarbon} I I I , a c o w r y o f th a work ohcnieal a tru a tu ra and carelnoganlo a c t i r i t y , and IT , a a u m try o f in ra a tig a tio n a on th a m etabolic fa ta o f rarlo u a a a tlh y d r o o a r b o n a . There la a rry axtanalra bibliography. 88. P la a e r , L. 7 . P ro d u e tlo n o f Cancer by P o ly n u c le a r H rdro- carbona. U nir. Poona. B icentennial Conf. Cauaa and Orowth o f Cancer, 1- 2? (1941) . A rariaw deroted to l-ao n taln in g oarcinogana, re la tio n of eareinoganle hydrocarbons to the s te rtld a . caroinoganic a o t i r l t y , chan, a tru a tu ra and ohn. ra - -2 5 - na,tu re f p o s s ib le re a c tio n le ad in g to carcinogeneai* and of th e n e ta b o lls a r e a c tio n * i f hyipooerbom co t>. , 5 d S S d . " In th e body by s te ro id a e ta b o llsm , t h e i r n o s t lik e lv ^ i n i t i a t i n g action of a hydrocarbon in involve au b atltu tio n in the hydrocarbon at I ts Boat reao tiv e cen ter, probably a lin k a L 1^ hydrarbon w ith an S-S t i ! S i ? f . th # , 0#U P*9* ^ * - M etabolio e lim in e - AuZZa * oarcinogan probably la a d e to x ic a tio n pro- * #ohtol>a d iffe re n t fro* th a t leading to f " 4 i T0lTin d i f f e r e n t p o in t o f th it *o1, Ith* r # a o t l n o i d e to x io a tlo n and ay lInSvLo lfvlel b i o l . h y d rotxry?latioPn^ tiot l ar ep.h enDoelitco xdiecarityio n or conversion into derive. of ercapturic a d d . * 34. W ***Sn-i* ?* P le a e r, M. C arcinogenlo Hydrocarbon, Organic C healatry", 1944, 814-lS 7^ TM n a . Caroinogcnlc a c tiv ity and a tru c tu re ; c o rre la tio n with c h z io a l re a o tiv ity ; nelhoda of ayntheaizing oarclnogenlo hydrocarbona. 35. f l r q u e t , i , and M a lte r, M. A. P itc h Cancer aa an O ccupational D iaeaae. Archive de Medeclne S oclale a t d'Hygiene n . "X & ; i i 5 S 5 * " * Phjr,l0l0` 1' * ! ? th o r! ,r ??o r t t h # l r ax p arten cea node in w edleal w orki^ w r i ,r< in province o f Liege, P itc h o r t a r . There were found two fniy no lung eanoera. T. Henry wade a chcmloal exM iination o f v ario u a p ito h e a aa to th e ir content in 1 . banzeneaathracene J l ! b e n z pyrene, ( th e two moat e f f e c t iv e oaneerogenie eubatancee in an iaala) and he found in th e p itc h l-g o f th e * * P t# 0.44 in th e second. The exam ination o f th e p itc h duet in th e two b r iq u e tte f a c to r le e re v e a l4 o r JO-IOOU, in th e ato ra g e roona tO i o f 80-50u. nttataiiAM Ik u k na--according to the authora--th a t 55 1. ? * h *** cane erogenic to aniw ala a re n o t i i w S 2 , t ^ t a ? ? iia rJ**er<*h U n*" **r* (* w a te ria l oi S f . i H r l i i S ? ) # r " r ** ** 3T. O a fa fa r, W M. and 81 tg reev e a , 1 . D isa b lin g M o rb id ity and *" 2*1 " a* f c P1y** o f O il l e f l n - f i,f a r 5 10# * **9* ibe and D uratio n , s88^ U#1T- U,S# a *P* , 1B1T- """ S K i c-- r. Bun. *hi9e"f . i o r t s Ut o , ih f o !,5 ,rT ,a "* o f n e a r mi s o r t <u t0 tb# nencrs of the road building syatm w ithoSut r e zl a t i o ?n to omRcedfam ro acdans.cer wee affirm ed but Hamilton, A lloa. Cnnoer fro Tar and Fetroleum . Poisons of U .E.", 410-7 ( m s ) " In d u s tria l Hamilton, A lloa. " In d u stria l Toxicology", 154, 255-4 Occupational oanear Is re ra in Franca. In tha U s 2}? 2 j y PuJlJ h o d ease up to 1980 was th e case of a ia n rt th* ? ,r*ffla * -- 1 the H ealth C o m ltta a -of tha League of la tio n a requested i t s Bombers to a id in a w orld-w ide in q u iry In to the ooourrence of occupational oanear by undertaxing a stu d y o f th e q u e stio n in t h e i r own c o u n trie s . The Hookef e l l e r Foundation th en made i t p o s s ib le f o r Imre H e lle r to melee an i n te n s ir e in T e s tig a tio n in t h i s co u n try , and iImi iprrlelsis?io^n h; ;e?lda P2byi l Al #mhe! ?ricalBn a19u3t h0`o r iHt iteUs #orn *e0a*n^o7er*.*ththaet 0TS * in 8re T*ry T,ry rare in th Tore h o s p ita ls s. Hp#o oflawlltinlgn in oratnoeoarrdonolyf 5th7e otawsoesleowf . op rroodduuccttSs,C*22f6tt 5o fi t th!Oe sUel4opc0c*u*riri?nl yg abm# otnrgmmc#edn htoantdalirn gandgasta r house t a r o r p lte h , o n ly two in coke-oran t a r o r p i t eh worker*. In a C lereland p la n t making carbon and dry * s11*h gas-h o u se p itc h was used up l t " * !, supplented by American coke-owen P p itc h . There ware 81 oases o f oanear among th e workers Oo iraa^nipilttoehh ," a^nd0^th o7 s4e w ferWe hnioeht weo#nr*sldlneremdm byh atnhdelinpgh ycsoickiea-n ln charge to be indubitable eases. pnyeician 41. H artw ell, J . L. Surrey o f Compounds which hare been Tested 3?I P?f (lS f l) lo tlT U y * * 8- *blin Health 8erriea, ^ h i* b u lle tin represents a surrey of the fie ld of ohemleal carol nogm iesls in th e higher animalsi the action tissu es, tissue eu ltS Is* protoaoa, end b a cteria la not eonsldered. 4he lit e r a tu r e i s eerered to 1989, and the com pilation a lso wi th^ 58 ocmpoxmAB from the unpub *** ** 8hr and Dr.'H . L. Htowart o f 22 The r e s u lts o f the t o s t- iFmli M IF reported, while ii * J*1 hole oanear lit e r a t u r e . A ltogether the work comprises data r e fe rr in g to eh l e a l sub- staneest o f th e se, 169 are reported to be earelnogenlo, A *67* p e r t from ZZ observed as causing p a iilo n e s only, t h i foTM J t r o J uJ t o r j d is c u s s io n , th e b u lle tin ta k e s ?. t- b u la r review on th e fo llow ing c la s a l- f le a ion (fig u ra a In p a re n th e se s show th* number of rsi* n f0i #aCf 0fct#r f 5i A* In o rg a n ic aubatancaa ^ "n ic compounds: I , A lio h a tio (36): I I f i i i n yC l1 1oy,c l i o / ^26^ t r i c y c l i c ' i47) , te tr a c y c lic ttt* 1 P ^n tacy cllo ( l i d ) , h ex acy o lic and h ig h e r (BZp.t c y o lic (59); 71, U n c la s s i1fYie*d (t770)l.4 (96) '7 , a t r i - *Pund* in d iv id u a lly i th a rouped aooording to p ro to ty p es and **b l*e tru ctu ral formulae, feraucea, p articu lars of species, strain , sex, and number of anim als used, p re p a ra tio n , dosage, and ro u te of a d m in istra tio n o f compounds, n a tu re of s ite s o f tumors induoed, m th d e ta ils o f d u ratio n of experim ent and tu r v iv a l r a t e s and o th e r r n a r k s . The above c o n d itio n s show th e wide range o f in fo rm atio n or?*r oaroinoganlo a o tiv ity of a given compound. The a u th o r draws a t te n t io n to th e incom pleteness o f th e d a ta f o r many o f th e compounds "* "** more a y a tn sa tie in v e s tig a tio n of PS r i < t t f " 4V i u41*d in * **U*ta*rr fa sh io n , and l a r * a ** " ong su b stan ees which i t d * iro b le to t e a t . The review i s completed by a b ib lio g rap h y (over 1200 re fe re n c e s ) and se p a ra te i s s '. p U s r a 't s i S t U . * " 11" *1" - t " ioim> C" " r* (ln ' lBd- p ie ohemioal p ro p e rtie s o f gas-w orks, ooke-ovmi. pro d u eer-fu rn ace and b la st-fu x n a o e ta r s and p itc h a re b rie fly o u tlin ed w ith a view to c o rre la tin g these pro- p i r t i i # to ean eer in eld en o e among workmen in th e <d u e tr ie s In v o lv ed . As a r e s u l t o f e x te n siv e surveys and n e e lth record eiu sn a . gas-works t a r and p itah^* were reep en eib le fo r TO.rf o f th e eases w hile ooke-oven t e r and p lto h were h e ld re s p o n s ib le f o r o nly 5 . 4%. Coke-oven t a r i s much th e le s s in ju r io u s e s p e c ia lly when cognisance i s tgkmi o f th e f a e t th a t eoke-ovm& t a r i s used much more e x te n s iv e ly . 5he p resenoe o f o le f in s ^* .***"*?rlc* , *4ml to bs o f p e r t l c u l s r im portanos b* omuas o f o i l o an ear. O oeupational aanosr dost n e t ooour in the b rip u et mfg. in d u stry . M ineral i 1!TM *"7 ** iaogenio a c t i v i t y acco rd in g to t h e i r ZT *??**! ^T***** c o n te n t. There i s no method f o r th e detm. o f th e smt. o f olofim s in th e 2 *121! I f 14! l f *uoh * e x is te d , i t would cancer-producing power of m ineral o ils . Center Is not a ttrib u ta b le to the occusa- because of the te re fu lly refin ed lu b rie e tin g o ils used on the n ech in es, thus in su rin g r e la tiv e freedom from o le fin s or unaatd. hydrocarbons. 4 ` H< -23A. Study o f P e ta l Caaes o f Canear o f th e 5ero turn. J . An. Mei. A sen., 109. 1667 (1957) 44. H iag*r, I . , Bpeotra o f C eaeer-produeing T ers and O il# and o f d e la te d Subetnncec. B ioehec. J . , 24, 505-11 (1950) 4 Hoffman, f . L. Mule 8pinnera C ancer. Monthly Labor H er. o f U .S ., 27, 457-475 (1958) 46 Hoffman, W. J . I n d u s t r i a l Canoer. P re v e n t. Med., 6, 7-54 (1956) One o f th e seven ty p e r o f in d u s t r i a l canoer"~diacuesad Is cancer of skin in workers exposed to coal, ta r , pitch, s o o t, s h a le , petroleum and a r s e n ic . They may cause en epitheliom atous fore of caseer. 47. Hogouneng, L. The C eneerlgenic Hydrocarbons from T ar end th e T errin* o f Hoads. 4 m . ly * . Pubi. S o cia le, 57. 1-7 (1959) The c a n c e rig e n ia hydrocarbons found in ooal t a r produce skin censer in exposed workers u su ally only a f te r d ire o t eonta c t w ith th e skin f o r lone perio d s of tim e. I t i s b e lie v e d th a t man la mush more r s i s t e n t to the action of these m eterais than lab . animala. 4S. Hueper , * . C. Censer in P e la ti to O ccupation and Inviro m ent. B ull. da. Se. Control Casar, 16, lo . 6 v/une, 1945) Ovine to induet r i e l development, th e ce n e re i popula tio n end fa c to ry workers in p a r tic u la r , are exposed'to many new m v lr o m c n ta l f a c t o r s , many o f e h i oh a re d iseese producing. O ccupational cancers are eeuaed by numerous oham icai and phya l e s i a g e n ts . Among thm i a re th e heery m e tale, n i t r a t e s , arom atic amino com pounds, benzol, asb esto s, m ineral o i l , aoot, ra d io -ac tiv e sub stan ces, u ltr a v io le t ra d ia tio n and X -rays. B is author c lte a e t e ti tie s taken m ainly from th e records o f in d u s tria l eomeerns, but p o in ts out th e ir ahsrteom Jjvs. Cm cer of the u rinary tr a c t dua to c o a l-ta r la the moat ra se n t ad d itio n to the l i s t o f occupational c a n se ra . I t i s m eet fragm ent in th e a n i l i n a Aya and related industries. 41. Heme O rfic a . R apt. o f B a p a rta o n ta l C om . to. O m aldor I v i dnoe e> to O ccurrence o f ^ p lfK L lm ia to u s Ule a r a t i am Among M ule-B pinners. (London, 1954) Contains a b ib liography on sanasi m m g p o tro la m refnera. * Hunt, I . 8 . An I n v e s t l a s t lem I n to th e In c id e n c e o f fa n s c ro is o r Presam oeroua S kin le s io n a Among T ar Yorke re l a l e v South Y ale s. Mod* P . A u s tr a lia , S .A d.5 3 , The g e n e ra l isnM O M ai l a t h a t t a r need l a la w South Vales fo r lo c a l road-vark la n o t a sariama danger. -1 9 - X* X. p . T. C areer B eseereh C o a a itte e . C& rci&ogenielty of S pindle O il* . J . I n s t . P e t. T ech ., S3, 803 11937) The I .p .T . CcEElttfr h*s n o t te e n convinced th a t the so -ca lled inoidenoc of cancer la in any shape o r fo ra connectec w ith the uoe of spindle o ils . 5f , I n t- r n a t io n a l Labour O ffic e . C a rc in o g e n ic ity o f O il* . In d . and Labour I n f o r a a tio n , 3, 273 (1330) Tere a t varying tem peratures have teem prepared to d e te ra in e a t what tem p eratu re oarolnogenio compounds a re formed, from which experim ents i t would appeex th a t suoh compounds begin to be foamed between 900* and tOO*, th e maximum y ie ld ly in g between 800* end 900*C. Attem pt i s now being made to determ ine th e c o n s titu tio n o f e few a p p a re n tly p ure o r alm ost p u re oompounde is o la te d from such ta r e . Applying th e ir standard te a t fo r determ ination of osreinogenieity, the s ta ff fount th a t o liv a o i l , n s e ta io o t o i l , sperm o i l were non-oaaoer producing and they h ere reason to suppose th a t n a tu ra l kin f a t i t an im portant f a c to r in th e prevention of -eanoer. 58. I n te r n a tio n a l Labour Off l e a . "O ccupation end H e a lth " , Z, 547 (1834); I I , 837, U M (1934) B efore m in e ra l o i l s came in to vogue th e p r a c tic e in t e x t i l e m ills was to use sperm, lo rd and n e a t'e - fo o t o i l s snd to seme e x te n t o a s to r o i l and e o lsa o i l . Henry s ta te s th a t ahale o i l was in tro d u ced about 1890 and Amarloan petroleum o i l about 1384, end th a t, towards 1972, th ese o ils were being used as eamponants of sp in d le o i l ; a ls o th a t Bussle a o i l was f i r s t im ported about 1839. B taanlaa o i l about 1900 and P ersian o i l about 1909, and a l l theso wore used f o r th is olaos of lu b ric a tin g o il before the war. During th e war S co ttish hale a l l s n a t u r a lly earns more in to u se f o r lu b r ic a tin g p u rp o ses. O il r e f i n e r s h a re t h e i r own p r iv a te foim ulee f o r m ixings, b u t th e ro i s no doubt th a t th e bulk of th e o il sold fo r lu b ricatin g spindles during the past fo rty y e a rs has baem p r in c ip a lly made up o f n a tu r a l m in eral o il. Aaoording to th e 1929 re p o rt of th e M anehostor Com er Committee, in th e d i s t i l l a t i o n o f t a r s , th e carcinogenic p ro d u c ts b eg in to f o r a a t a tem p eratu re ran g in g from 900 to 600 C. end reac h e w l i m a t between 800 end 900 0. The a d d itio n o f s u lf u r ie e e ld e t th e tim e o f u se s u ffic e s to make th e o i l s hmxmleos w ith o u t in ju r in g o r m odifying t h e i r lu b r ic a tin g power* 34. I n te r n a tio n a l Labour O ffic e , O ccu p atio n al Tumora. Buppl. to Oeeupatlon and H aalth , I.L .O ., Qanera (Oot, 1999) Carcinogenic oubstanoea e re dlearnssad under the h eadings o f h y d ro carb o n s, a o n -ra d lo e s tiv e in o rg a n ic earn* pounds, rad io activ e substances and ra d ia tio n , and parenttoo f&L -3 0 - and m icrobes. A tten tion i s c a lle d to the absence o f any ecm on physical or ohmnioal c h a r a c te r is tic s shared by there v -rio u s oanoer-produeirg ag en ts. I t i s suggested that the cancer problem i s e s s e n tia lly biochemical sad that i t s solu tion w ill ooao with tho discovery o f the neture end osus* o f the in t r t - e e llu le r chemical changes which follow the ap plication o f s oireinogenic agent. . Jordan, E. Experimental stu d io s on tho Production o f Canoer 9 * by Gas-works Ter. Z. Xrebsfortahung, 19. 39-55 (1932) Author has corroboreted tho work o f others) in w hits a io e treeted with t s r fo r four months or lo s s , 1004 showed e ith e r c a n c e r p r o o a n c e r o u s ohanges. Whan tho ta r was fiietd . a t 400* tho v o la t ile fr a c tio n did not produce these ohsnges but tho residue produced the ty p ic a l p r o life r a tiv e ehsagot in bout 1/1 the time re quired with the whole te r . l o p r o life r a tio n could be produced w ith anthracene o i l . D iffe r e n t mice showed m narked d ifferen ce in the rap id ity with whieh they developed p r o life r a tio n with tho same emt. o f in ju ry by the t e r . Apparently th e work wes not follow ed to a p oint dip d ot. ju s t hew many o f th e miee w ith presen ceret:s changes would hove developed a ctu a l carcinoma. 14, Isnacwey, Z. L. The formation o f e Oaae-r-prodicing Substance from Xsoprene. J . Path* l a e t . | , 135-6 (1924) fH. Xawahata, X. Lung Cansor Among Generator-dae lorkare im the S te e l M ills . Gann. S t, S4T-68 (1938) ^ During tha peat 6 y ea rs, 31 eesee o f primary l o g cartlgoha. were observed ameng the gsm eretor-ges workers at the Taweta X r sn -fte e l M ills . These workers haw# aw. se r v ic e periods o f 13 y ea r s. In me eth er seetlam e e f the m ills has such frequent appearance o f lwmg causer been m otieed. The workers are exposed to th e sprayimg o f ges eea tg . heavy duet The Inhaled gaa eontelaed about 0.74 o f gaseous or d n e t-llk e ta r . Analyaoa showed creo so te o i l 3 4 .M ll, phenols 0 .3 1 4 , o reeo ls 0.074. aaphthol 4.004. aathreseme 3.004, pitch o i l 68.173 and water 9.744 D ie m etestaeee may appear v ir y ea r ly in the b ra in , sp in a l so r t and ljmph nodes. The duration o f lung sender i s w r y abort, about 7 months. IT. Xsmmaway, 1 . 1 . Canaer-Preduoing Comstltwemts e f Goal Tar B r it. Med. 534-7 (1034) Cancer formation by ta r products wes in v estig a ted by author. Only higher fr a c tio n s b o ilin g a t 390-500*6. ware found a c tiv e in inducing emmeer (e r e o e o te , gresm o i l , orude antraoeme end p it c h ) . -51- ie n n away, I . L. Cancer-Producing Tare and Ter f ra c tio n s . J . I n i . Hygiene , 468--J3 (1024) E xjerim ents on se v e ra l thousand ir.ioe and a n a ly s is of a g r e a t msec of o lin io e l re c o rd s in d lo a te th a t t a r oancer i s cauped by a very n a i l q u a n tity of an u n sta b le conpound th a t e x is ts in th e h ig h -b o ilin g f r a c tio n (880* to 500*) of a high-tem p, coal t a r , l . e . , creosote o i l and an th raoene o il. P u rifie d anthracene, lik e a l l o th er pure ocapounds tr ie d , did not produce eanoer. Splashing v lth h o t, crude anthracene o r creo so te o ils seems to be th e usual method of co n tact. 8hale o i l produces cancer but i s le s s a c tiv e th a n gas works t a r ; crude petroleum i s much le s s a c tiv e ; and b la st-fu rn a c e t a r (a low-temp, ta r) does not produce eanoer. The b r iq u e ttin g In d u s try has re p o rte d more th an h a l f o f th e known oases o f t a r ean o er. Tar made by d i s t i l l i n g ooal a t a low tem p eratu re (below 550*) produces cancer very slowly or not a t a l l . 59, Kennawey, Z. L. Experimenta on C encer-Produelng S ubstances. B rit. Hed. J . , I I , 1-4 (1985) Cancar has been orodueed ln mica by substances obtalned by h e a tin g C*Ht , iso p ra n o , y e a s t, human akin to tempe, ran g in g from 700* to 980*. A Petroleum whloh produeed no tumors o f any klnd ln mica in a prolongad e x p e rln c n t ahornad very e stiv a eaneer-produelng p ro p erties a fte r exposure to 880*. 10. Kmeway, 1. L. and l e i t e h , A. The A natcm ioal D is tr ib u tio n o f th e O ccupational C ancer. J . In d . Hygiene, , 69 (1985) 61. I annaway, A. J . f u r t h e r Zxperim ents on C aneer-Produelng Substanoes. Biochan. 1 ., 84, 497-504 (1950) Carelnogenie substances were obtained by th e a c tio s a t roam tem p eratu re o f A1C1 on a o c ty le n e , x y len e, n ap h th alen e, naphthalene and bronobcnxane and tetrahydronaphthalene, th e l a s t two being th e most a c tiv e . Two canoero were a lso o b tain ed in a s e r ie s o f 10 mioe p a in te d w ith a co in , of l,2,7,S*dibM sam thraocne. a-P henylnaphthalsne was prepared by a c tio n o f AlClt on CaHt Br and CA#l a . The d i s t i l l a t e s a p t o 548*C. eoa- ta in ln g the hydrocarbon were in a c tiv e but th e resid u e ln th e f la s k was h ig h ly eereln o g sn la. Cyclohexane, cyclohexane, sty ren e, hydrophmaanthrone, hydroohrysene, h y d ro reten e, p ery lc n e, naphthalsne end i various naphthalene deriv ativ es a ll gave negative re su lts . i 68. Kenneway, X. L. end H leg e r, I . C arelnogenie S ubstances and T h e ir flu o re sc e n c e S p e c tra . B r i t . Med. J . , Bo. S68I, 1044-6 (1990) T his paper i s a review o f a la rg e amount o f work by the authors in an attem pt to c o rre la te fluorescence with carcinogenesis. T ar o i l s , sp in d le and sh a le o i l s , which show carcim o- genie properties are also strongly fluorescent. J J lew ley , J. C ooperation. J. I n s t . P e t. T ech ., 13, 242 (1332) M ention of the foim etion of a committee by th e I n s t i t u t e o f Petroleum T ech n o lo g ists to fo llo w th e woric of the M anchester Cancer Committee. K llng, A ,, Samasonow, H. and fiero s, M. The T arrin g of Highways as a P o ssib le Agent in th e C ausation of Pulmonary C ancer. B u ll. Aoad. Med. 120, 130-43 (1938) Expt. in mice showed th a t th e t a r , as used on ro a d s, produoes cutaneous tumors and malignanoy in the lungs. A substance oontg. the benzo (a) pyrene nucleus of decidedly canoerogenic p ro p e rtie s has been sepd. from the ta r. g5. S lin g , A ., Samssonov, I . and H eroa, M. P o s s ib le B e la tlo n sh lp t between T arrin g of Highways and th e In c re a se o f Inoldenoe of Pulmonary Prim ary Cancer. B u ll. Aead. Med., 121. 784-91 (1939) Since ta r contains benzopyrene, a recognized oanoerlgenic agent, I t cannot be considered as inoffensive. Ixperim ente on mice d e f in ite ly confix* th is aesvmptlon. 66. S oelech, 7 . Cancer end O ccupation. M onataohr. Ire b sb e k a n p f. 5, 7 (1937) " The a u th o r, in th e form o f an a b s t r a c t , p re s e n ts e su rrey o f the r e la tio n between oenoer and occupation. Ha in o lu d a s bone cancer eauaed by r a d io a c tiv e su b sta n c e s, aJcln osneer from e o o t, t a r , p a r a f f in and lu b r lo a tln g o i l s (o f which those b o ilin g between 250-500* are of e sp ecial im portance), akin cancer from a rse n ie es w ell as oaneer and sarooma from u l t r a v i o l e t end s u n lig h t. 67. Eunze, 0 . M ineral O il and Cenoer. Cham. Z tg ., 59. 407-8 (1935) A stu d y o f th o map o f Oexmany in d ic a te d th a t th e number o f d ea th s from eanoer was always g r e a t e s t In re g io n s where m in e ra l o i l wee found, r e f in e d o r usod. While no d e f in ite r e la tio n i s e s ta b lish e d , th e author suggests the p o s s ib ility o f tho existence of aueh a re la tio n sh ip , fu rth e r research on th is problem la in d ic ated . I t is pointed out th a t m ineral o il by i t s e lf does n o t eauso eanoer. I t may, however, beocme one of tho o ontrlbutlng fa o to rs, to g eth er w ith o th e rs. M. Lane, C. 0 . O ccupational D e z m s tltls . A rch. D o a u to l. and M S y p h il. 43, 184 (1941) 4 D escribee th e e sse o f e 48 y r . o ld m a c h in ist who fo r i 3 y re . had a d c x s a tlt is o f th e fao e( a n te , a x i lla e and low er abdomen. There were s o a tte re d a re a s o f tan-brown h y p erk erato tlo f o lllo le a and f o l l i c u l a r plu g s. K eratoses war# p rese n t on tho serotwn and thoro were k e ra to tie areas on tho axma. Autopsy revealed carcinoma of tho esophagus. D r. Lama b e lie v e s th e akin changes to be due -SS to o i l to which th e man wma exposed in h la 40 y re . aa a m a c h in ist, and th a t th a c o n d itio n ia t h a t d e sc rib e d by White emong m a c h in ists, o i l w orkers end mula sp in n e rs in fcxgland. I t ap p aren tly i s m r w l y seen in th is country, p o ssib ly because o ils employed here a re le e s carcinogenic. t a u t e r , H .J ., H ild ebran d , X. and Sehocke, H. P o s s ib le Therapeutio A ction of Ceroinogenlc Hydrooarbona in Treatm ent o f C ancer. Z. Gas. X xptl. Med., IP S . STO-94 119 39) X ssentlally le ss harmful therapeutio measures are a v a ila b le . The dangers a re dem onstrated on miee tr e a te d w ith m ethyloholanthrene. a L e lto h , A. Mule p ln n e ra ' Cancer and M ineral O ils . B r it. Med. J . , X, 941-3 (19S4) B enderai an i n e r t C a lif o rn ia o i l very a c tiv e by h eatin g i t . (lo d e ta ils as to tem->*r*tur*, a t e . ) . Cruda e l l s from Assam, Borneo, Ig y p t, Bum s and Badarpur produca m alignant growths. G alician, Ausaian, C a lifo rn ian and P ersian sa a p lss wars n e g a tiv e . 71. Lyth, A. The Bel a t ion o f C arcinog a n ic i ty o f M ineral O lla to C ertain P hysical and Chemical C h a ra c te ristic s of Those O ils . J . o f In d . Hyg. 15, ttd -S T (19SS) Tt. L yth, E. M oleouler D i a t i l l e t i o n o f L u b rie s tin g O il. S a tu re , 139, S74 (1937) A b r ie f r e p o r t ie given of the d is tilla tio n of a S cottish ahals o il, using s spoolally designed molecular s t i l l . The moat s tr ik in g r e s u l t i s th e in v e rsio n in th e change in the physical p ro p e rtie s going up tho tempera tu r e s c a le , i . e . , th e f i r s t f r a c tio n s show h ig h e r r e fra c tiv e in d ic e s end d en sit ie s than th e o rig in a l o i l , w ith g rad u ally descending values from f ra c tio n four as the tem perature i s ra is e d . Bate on th e p ro p e rtie s of the sh ale o il d i s t i l l a t e s are ta b u lated . These experiment* ere p a rt of an in v e stig a tio n o f th e in te r r e la tio n o f re f ra c tiv e index and v la e o s lty to a o tlv lty on in je c tio n , end th ereb y o aro ln o g an lo lty when a p p lie d to th e s k in . 73. M issc h sr, O ., Almasy, V. and Zahondar, Z. I s Thera a Connection Between th e Benzpyrene Content end tho C eroinogenlc X ffec t o f Text ic h w e is. Med. Wohnsohr. 71, 1001-7 (1941) The au th o rs have e x n ln e d th* benzpyrene co n ten t o f gae t a r in v a rio u s towns in B w ltsarland, using s method devised by Almasy. Then th o ta r e were p u rifie d and th e ir eareinogenle e f f e c t determ ined by p ain tin g on m iee. The in v e s tig a to r s t r i e d to e v a lu a te th e r e s u lt s by means o f s s t e t l s t l e e l method in o rd e r to overcome th e d i f f i c u l t y o ffe re d by th e f a c t th e t many mice d ie in the long period needed fo r the experim ents. They fin d a s ta p le , r e g u la r r e la tio n s h ip between th e benzpyrene co n ten t and th e c a rc in o g e n ic ity Of th e t a r . ql' Murray, J. a. , e t a l . D iscussion on -Toeri&entel P roduction o f M alignant Tumors. P roc. Boy. Soc. (London) BU S . 268-92 ( 1933) A symposium in eftiich some a t te n t io n i s p aid to oarcinogenlc ehsm. compounds, and to th e immunochemistry of cancer. ^3. O 'B rien , H. I , The Problem o f Canoer and O il. Petroleum Time*, 27, 462 (1922) An open l e t t e r to th e e d i to r o f th e Petroleum Times (London) in answer to an e d ito r ia l in the issu e of March 1 9 th . The w r i te r p o in ts o u t th e h u m an itarian and s c i e n t i f i c v alu es deriv ed from th e cancer research of th e M anchester Committee end o r ltic lx e d th e teohnolo g lo el viewpoint of the e d ito ria l. 76. O'Donovan, V. J . Cancer from Handling A n th n o en e Coke in th e Dye I n d u s try . Br. J . Dezmat. and S y p h ., Three oases of cancer in a fa c to ry employing only 29 man. 77. P h i l l i p s , C. R e la tio n sh ip between Skin Cancer and O ccupation in Texas: Review o f 1569 T e r if le d L esions O ccurring in 1190 P e tle n ts . Texas S ta ts J . Med., 36. 613-16 (1941) 78. P r o s s e r - lh i te , . "The Dezmatergoees" 195-236 (1934) . D erm atitis and canosr from p e tro le u s produota, shale end ta r s . Ix e e lle n t rsvisw . 88, R offo, * . h . Ix p e rim sn ts l R esearch on th e P ro d u ctio n o f Pulmonary Tumors by th e D i s t i l l a t e s o f P ual O il. P ress# Mad., 538 (1940) The a u th o r dem onstrated an o i l , taken from th e s tr e e ts o f Buenos A iree, id e n tic a l to th a t from motor car exhaust, wfaiah sonta in s c a ro l nog en ic su b sta n c e s. Roffo had n i f K in h alo th e combustion gases o f fu e l o i l end l s t e r found e mmsber o f pulmonary sa n eers among th e an im als. By in jectin g e d is tilla te of the fuel o il into the au ric le o f r a b b i t s , he produced tumors in QOi, 81. Rousay, 0 . and O b erlin g , C. Can T a rrin g o f Roads be Con sid e re d as s Cause o f Pulmonary Caneer? B u ll. Aocd. Med. 120, 161-90 (1936) The danger i s n o t eo n sld ared to be o f s lg n iflo a n e e although the p o ssib ility is adm itted. 88, S chreue, H. T. and Z u rh e lle , X. X xperlm ental P roduotion o f Tmeors w ith Tars from Verioue ouroas and w ith P a ra ffin . D eut. Med. T ochachr. 49, 633-4 (1923) Author in v estig ated th e poisonous eetiom of p a ra ffin -3 5 - o i l and t a r c o n s titu e n ts by p ain tin g lo a tw ice a weak. A ft r six month a a ta ta of malignancy aa o btainad w ith p e re ffln o il. Coal ta r re a d ily develops m elignant tumors. Varioua p u rifia d acid and baaio fra o tio n a from ooal ta r glTe n e g a tiv e r e a u l ta . The n a a tr a l t ix o i l ! moat e f f e c tiv e na a tumor in d u o a r. 85* Sohw arts, L. Skin D iseases in O il k e f in e r ie a . efaty I n .. 210 (Bov. 1324) I t haa baan found th a t workers in o i l ra fin a ria a have a parcantaga above tha average fo r oarcinone of tha cheek and o f th a l i p . An unusual p rev alen ce o f pigmantad p a p il loma t* on th a hands, forearm and la g s o f w orkers in o i l r a f in e r ia a and among m a c h in ists in o o n tao t w ith o i l and g reaaa was a ls o n o ta d . About 10$ o f such w orkers wara found to have thasa growths. Tha usa o f t o t a l l y anelosad m anufacturing system s and of p ro teo tlra ointm ents is suggested. 84. Sohw arts, L. and T u llp an , L. O ccupational D iseases o f tha Skin f 1939, 14 85. S c o tt, A. O ccupational Dermatoses o f th a P a r a f f in d o r te r s in S c o ttis h S hale O ils . B r i t . Med. J . , 3 .2 8 .2 1 , 301-5 86. S c q u c ira , J. H. Cancer and o th e r D iseases o f th a Skin Caused U 9 2 9 )erl 0 i l ** ***** * A fric an Mad. J . , 6, 18-13 87. Smyth, H. J . Review o f L ita r a tu r a f o r 1916-1934, in e . Report of C oanlttec on In d u s tria l Skin I r r i t a n t s to Am. P u b lic H ealth Assn. 88. Southern and W ilson. Cancer o f th e Scrotum. B r i t . Med. J .,, 1, 971-3 (1911) 1 8. Speeknan, J. B. and Cham berlain, I . I . T ran s. P srsd sy So.,. 19, 367-8 (1933) * In s study o f tha eeroinogenlo potency of m ineral o ils , Twart has ahovn th a t th a ad d itio n of glyeerldea raduoaa th e ir potency, although no o i l aurpaaaea lanolin in th is respeot. 10. io lo k y , L . O oeupational C ancar. A cts d . I n t e r n a t . Te r . f . Krebsbekmpfung, 3, 133-75 (193B) S e v e ra l is o la te d aaaaa o f lung can cer among g e n e ra to r w ort ora h ero boon re p o rte d and aatong w o rts sxpoaod to coal d u st, t a r and t a r d i s t i l l a t e s , but tha number la asall. t l . T eu tao h laen d er, 0 . I n d u s t r i a l Canoe r , e s p e s la lly th e Typaa O ccurring in Germany. Z. f u s r K reb ifo raeh . 31, 614-29 (1930) --^ Dleousses x-ray aanear, oanear of b rlq u o tto workora, -35mule pinner' cancer, which h** n o t appeared in Germany, 2nd p a r a f f in cenoer among th o se who work in the petroleum in d u stry . ol. T utsohlndr, 0 . O ocupational Cancer, w ith S p e c ia l Con- 9 * s id a r e tlo n o f i t P rsv e n tio n and L e g is la tio n on th S ubject, ed. b e lt, 11, 1867-78, 1341-5 (1937) Occupation in whioh th e re 1 danger o f development o f can cer are review ed; many d ata a re given reg ard in g ubatane ' considered e a re in o g e n ie , th e lo o a tlo r of m alignant tumors, th e ir la te n t period, p ro tec tiv e measure of an in d u s tria l-h y g ie n ic ty p e , g e s t i o n s of in su ra n c e , e to . There i s no so . ag en t common to a l l cerclnoger.lo substances as a promoter of oanoer growth. g( T eusohlaender, 0 . Does Ter B aqulre U ltra V io le t L ig h t to Produce Skin Cancers K lin . Wohnsehr., 16. 1884-5 (1937) White mice were painted w ith t e r . Canoers developed not only in the irra d ia te d animals but also in those kept in a dark chamber so th a t no t only a p rep arato ry but also an independent caneerogenic e ffe c t must be ascribed to ta r. 94, T eu tseh la en d er, 0 . L ig h t and Skin Cancer. Z ts e h r. f . K rebsforsoh, 50, 81-98 (1940) The au th o r in v e s tig a te s th e p ro b lo i o f w hether o r n o t a photodynamic in flu en ce ls a p e s s e r y in the geneals o f t e r o an eer. He eondueted experim ents on ta r r e d mice k e p t in e darkroom. S inee ak in oaneer developed on th e painted kin, i t la evident th a t u ltra -v io la t lig h t la n o t a r e q u is i te in t a r oaneer g e n e a ie . The seme i s shown by th e development o f apontaneoua ak in ean eere in two wild grey house n ice th a t lived in e b riq u et faotory. lev erth eleea th ere la e widescreed b e lie f th a t both oanoer of rad ia n t soures and ta r oaneer o f th e ekln are caused by a y e lle hydrocarbons. According to B offo, both types e re o rig in a te d by o x id atio n and decom position of e h o ls s ts r o l in th a t l s s u s s which may be eaueed by ra d ia tio n as w ell ee by ehemleal in flu en c e-- eanoerprovoking oyelle hydroearbona are f la e lly generated. P rophylaxis mmst, th a re fo re , guard a g a in s t th e in flu en ce of one or both fa c to rs. 99. T o u rain e, A. end Bout, H. Cancer from L a b rio a tin g O lle . B er. Med. y ran c. 80, 885-98 (1989) A very eomplete review of eenoer from lu b ric a tin g o lla , i t e o eo u rren ee, c l i n i c a l symptoms and th e a e d lo o -la g a l ap e o te o f amah caeca. 96. Tw ort, C.C. end la g , H.B. Mula Bplnnsrs* Cancer and M ineral O lla . L anest 1 , 758 (1988) -3 7 - Twort, C.C. and F u lto n , F . B. Experim ents on th e Mature of ' th Carcinogenic Agents in * in e re l O ils. F. P rth . an4 B a c te rio l., 32, 149-161 (1929) From a c o n s id e ra tio n o f th chem ical re a c tio n involved, th authors are of th opinion th a t i t is to benezenoid hydrocarbons th a t c e r t a in m in eral o i l s ow th e ir cerelnogenio p ro p e rtie s. Treatment of th o ils with sulphuric acid ld to almost to ta l ab o litio n of th ir oeroinogenle p ro p e rtie s , and s im ila r r e s u lt s war obtained by th e adoption o f methods o f o x id atio n and reduction. 99. Twort, C.C. and Twort, F. K. S tu d ie s or. th e O rig in ot C areer. Z tsc h r. f . K re b efo ra ch ., 32, 491 (1930) This i s ' a g e n e ra l su rre y o f th e work o f th e Tw orts, *nfi i s based on experim ents on 43,000 a lo e , a sm a lle r number of r a te , g u in ea-p ig s, and r s b b its , end on the use o f some hundred o f v a r i e t i e s o f ta r ? end o i l s o f v ario u s ca p ac itie s to cause oaneer. There is but l i t t l e pro b a b ility th a t an acquired p h y sio lo g io al immunity a g a in st oaneer-producing su b stan ces e x i s t s . The a u th o rs ' v ario u s substances are divided according to th e ir osnosr-fonalng capacity in mice, to th a t every group has about ten times th e power of the preceding one. 99. Twort, C. C. and Twort, F . M. U g a s i f io a tio n o f Four Thousand Sxperlm ental O il and T ar Skin Tumours o f Mice. The stu d y from which t h i s c l a s s i f i c a t i o n was mads was bsssd upon 9,100 anim als. 100. Twort, C. C. and F u lto n , F . &. F u rth e r Experiment on th e C arcinogenicity of S ynthetic Tara and Their F rcotlons. F. Path. B eet. 33, 119-42 (1930) 101. Twort, C. C. and Twort, F . M. The C erelnogenio Potency of M ineral O ils. F. Ind. Eyg. 13. 204-22# (1931) P ain tin g miee w ith refin ed aEsle o i l indueee cancer more re a d ily than p a in tin g w ith re fin e d petroleum w ell e l l . The moet p o te n t f r s o tlo n from sh a le o i l l e un fin ish e d lu b ric a tin g o i l from which moet o f th e p a r a f f in wax hae been removed b u t which had n o t been tr e a te d w ith Ha804 end f i l t e r e d . The h e a v ie r grad e o i l s e r e le e s p o te n t th an sp in d le o i l s . The oanoer- preducing property of o ils appear to be rela ted to flu o re e c e n o e . O ils having e b lu e flu o re se e n o e eeem more a c tiv e than th o se having a green flu o reso en o e. Chrysene dissolved In o le le sold possesses oarelnogcnlo p ro p erties. Twort, C. C. and Twort, J . X. The B e la tlv e Potency, o f Cerelnogenio Tara and O ils . F. Hyg., 29, 273-9 (1931) A method has been dev ised vftiereby tKe potency of any given oerolnogenle agent can be compared w ith th a t of e standard agent. A u n it of earelnogenloity- U.C.- T 103. : 104. : '1 -3 J- has been e s ta b lis h e d , and a c o n c e n tra tio n of 600 carcinogenic u n it3 per cubic centim eter la considered to Induce the maximum r e le tlT e response in anineLa when th e agent la ap p lied tw ice a weex. The c rcin o g e n ic cowers of o i l s r a t e aa fo llo w s, in descending order: Shale, Venezuelan, Borneo, Rumanian, P araia n , C a lifo rn ia n , Mexioan, Mid-oontin e n ta l, Texan, P e n n s/Ira n ia n , and iu a a ia n . Hypothetical standard agent Penn, o il Cal. p et. o il O il Ho. 3 100.0 0.1 3.0 0.6 Shale O il 48.0 P itc h 25.0 Gas t a r 94.0 Pinene synthetic ta r Effect of refining 706.0 Penn, o il 0.1 Methyl s u l f i t e e x tra o t 22.0 O il Ho. 3 0.6 D i s t i l l a t e 300-380*C./lmm 12.0 Methyl s u l f i t e e x tra o t 53.0 Shale o il 46.0 Oxidized s t 150-160*C. 0.3 Pinene sy n th e tic t a r concentrate 3746.0 Oxidized a t 100*C. 2369.0 Oxidized a t 150-16C'C. 68.0 Twort, C.C. and F u lto n , J . 3 . C oncentration o f th e C arcinogenic P r in c ip le in O ils and T a rs. J. fu e r X rebaforseh. 36, 643-73 (1932) In th e attem pt to a s s e s s U.C. by p h y aleal and chssilcal c h a ra c te ristic s, the sp ecific g rav ity , re fra c tiv e index and io d in e number appeared most pro mi sin g , though o th e r f e a tu r e s may a ls o u ltim a te ly prove to^of value. Twort, C. C. and Iyth, K. The S e le c tio n o f K on-oareino- genic from Carcinogenic O ils . f . Hyg., 33, 464-73 (1933) A ll th e animal end veg etab le o ils te a te d by the euthors on anim ale have proved to be lnoapable o f in ducing tumor form ation during the l i f e o f th e ir an im als. On th s o th e r hand, o le ic a d d and l i n o l e i e a e ld , u n s a tu ra te d f a t t y s o ld i which may be p re s e n t in ocomerelal saponifiable o ils , have frequently Induced txraor form ation; obaervatlone which in th e ir opinion a rs o f the h ig h e s t im portance in r e l a t i o n to many oaneara o th ar than thoea o f tha akin, and possibly aven o f thosa o f th a skin i t s e l f . I t has baen found th a t tha earclnoganlo o o n stltu ccts of a given crude are not equally d istrib u ted in the various products o f d l s t l l l e t l o n obtained from th is cru d e. The a c t i v i t y o f th a f i r s t p ro d u c t! to coma over -39 in th* t i l l , th# no to r p irita , e tc ., is n e g lig ib le , end th a t o f th# lamp o il* , burning o i l s , l i g h t f u e l, e t c . , 1* a ls o o f l i t t l * account} b u t when w# roach th* boiling range of th* lu b rica tin g o il* a d e fin ite CTroinogsnio -.ictiv ity mry become m a n ife s t. Among th* l a t t e r t.i* most a c tiv e grad** e ra , on th* whole, th* sw indle ,'r a l i s , c lo s e ly follow ed by o il* o f a Redwood v is c o s ity of 500 to 1500 a t 7 0 * ?., w ith a g rad u al decreae* in a c tiv ity as on* approach** th* in te rn a l combustion engine (m otor c a r) g ra d e s. Th* crudo o il* them selves, as a r u le , ar* somewhat l* s* o o ta n t than th* motor oer o il* , but of ooura. I t w ill n*ceaaarily depend upon th* amount o f re fin in g to whioh th* l a t t e r have been subjected before being m arketed. 105* Twort, C.C. end Twort, J . M. C e ro in o g en ic ity o f S p in d le O il* . O il end Colour Xrndea J . , 9, 1193-4 (1937) A physical and an animal- t e s t f e r ca rcin o g en icity and e p h y sical *nd an animal t e s t f o r d e r a a tie ity o f m ineral t e x t i l e o il* .a r e d escrib ed . The average re s u lt* o f the** t e s t s on 64 o il* ( gxeludlng *hsl* o il* ) ( c o lle c te d 5-10 y rt.a g o end on 66 o il* ooll* o t* d re c e n tly a re ta b u la te d . (Th* anim al t e s t f o r e a ro ln o g e n ie ity i s n o t y et completed fo r th e reeen t o il* .) These re su lt ia d ie a t* th a t tn* o rig in a l o il* a re d a f in lta ly wora* than tha recent o il* In both th* dazm atltl* t* * ta, w hile in th a canoar p h y sical t e s t th e re la no s ig n if i cant d ifferen ce. I t is expeoted th a t th a fig u re s fo r tha UI reoent o ils in tha animal te s t of earolnogenlolty will, ba lover than those of the o rig in a l o il . I t i s concluded, however th a t l i t t l e la being done to improve au le sp in d le o il* from th a b io lo g ic a l stand p o in t. zfcare aro also in d ic a tio n s th a t th a average o il uaod in some o f th e codton*#pin n in g town* i s more dangerous than th a t used In e th e rs. \06* 01 T e o rt, C. C. and Twort, J . M. lo t a a on Soma o f th o Procedures Adopted fo r A ssessing th e B io lo g ical A o tiv ity of M ineral O ils. O il Colour Tredoa J . , 94, 861-6 (1930) M in eral o i l s may induce d e r m a title o r cancer o f tho kin. In dotg. tho carolnogenle aenaet 3 e sse n tia l data*, ar* mads: d . , n and k ln e tlo v ia o o s lty ( iT ) . The d a ta ooU eeted ar* based on tho u tilis a tio n o f form ulas fo r a s s e s s in g th * M o l. a c t i v i t y , o a p a a la lly from i t s oar** oinogania s a p a e t. I n form ula A, ! ( n - l ) / d e h a ra Mm sp. r * f r a c t i v i t y , xw r e f r e o tiv a index and d d e n s ity . In Formula B, 1 n - ( d / f ) . form ula A I s used in o b t a i n ! ^ th a aanoor r a f r a e tlv l ty Cl from form ula C which la Cl B*S( d-0*900)/K ). I n form ula 9 th a r e f in e d eanoar r e - fre a tiv ity (ST/5 0 ) . B a a u lta , where th e s e m ineral o i l s have been employed, a ro shown in ta b le * in which m in e ra l o il* ar* grouped aooordlng to t o x i c i t y and A \T S * -4 0 - aeoording to th e n drop, The s ig n ific a n c e o f d . in r e la tio n to th n drop among o i l s o f lm l lir to x io ity and th sig n ifie e n o e o f v ie o o e ity in r e l a t i o n to th n drop among o i l s o f a p p a re n tly s im ila r to x ic ity a r ahown. Ih e r e a l d i f f i c u l t y in r r r iv in g a t th e tr u e b io l. a c t i v i t y w ith g r e a te r accuracy l a th lac*; o f uniform ity of the im rt fu lly hydrogenated co n stitu ent. E iero is q u ite good c o rre la tio n between car c in o g e n ic ity , r e f r a c t! v ity , n drop ad t o r i c i t y . joy. Twort, J. M. and L yth, R. Th C onoentretion of Ci.ro inogenio M a te ria ls in M ineral 011 by D ie t illa tio n Process. J. Hyg. S9, 161-9 (1989) Twelve a c id -tre a te d lu b ric a tin g cut o f a erud, Borneo m ineral o i l , were te s te d f o r oarcir.ogenlc o tiilty . The whole range was b io lo g ic a lly s a t i r e , which a c t i v i t y had bon fo reseen from a r exam ination o f th p h y sical c h a r a c te r is tic ! :. The peak a c t l r l t y was around a v is c o s ity o f 800-250 C an tlp o lses a t 88*C. M olecular d ia t l l la t lo n gave a g re a te r concentration o f the carcino genic m a te rie l than o rd in ary d is t illa tio n * a t from 5-10 am. In co nfirm ation o f previous fin d in g , th e m iddle fra c tio n o f e Borneo crude o i l ware m ostly resp o n sib le fo r pathological changes in the organa-- fa tty in f ilt r a tio n of the liv e r and hyaline degeneration of the spleen. Lung tumors were more p re v a le n t th en i s u s u a l when t h i s type o f agent ia used fo r te stin g earelnogealty fo r the k in . T h eir in e id e n e e was r a t h e r h ig h e r in th e more v isc o u s fra c tio n s } t h i s in cid en ce was a p p a re n tly n o t co rre la te d with eareinogenity fo r the skin* 106. T v o rt, J . M. end L yth, S. Skin Cancer due to H andling Coal T ars C6d f o r P re s e rv a tio n o f P ish in g 1 s t . M ature, 144. 446 (1989) S everal fishexmen contracted osneer o f th e akin a f te r h an d lin g th e t a r s . Mouse e x p ts. showed t h a t d if f e r e n t oosl ta rs d iffe re d in th e ir oaroizxogenie a c tiv ity , although a l l produeed eons eaneera. C reosote o i l and anthracene o i l were a lso oareinogenlc. Only ooal t a r made i n v e r t l e a l l o w - t a p . r e t o r t s should be used on n e t s . Twort, c . C. M ule-Bpixmere' Canoa r: The food f o r Using th e C orreot O ils . O il-C o lo u r Trades ? . , 8 .2 9 .4 1 , 386 The oanoer-prodnoing powers o f m inorai o lio used in th a co tto n in d u stry from d if f e r e n t f ie ld s o f o r ig in , in th e orude and re fin e d s ta te s , were thoroughly exanlned and th e r e s u l t s showed th a t th e r e l a a danger of any one producing oar-car of th e skin i f applied long enough but th e o i l s from c e rta in f ie ld s a re the more l i k e l y to do so . S p e c ia l a tte n tio n was p aid to the examination of tha physloal eh araete r i tie s of v a rio u s m in e ra l o l l a , and i t was proved t h a t e knowl edge of th e ir re frn o tiv o index and v is c o s ity provides T -41- a more r e lia b le estim ate o f th e ir canoer-produolng powers then the a p p lic a tio n of the sample to the akin. Thie te s t is accu rate, rapid and inexpensive, while th a t v-ith the eicir. la v a r ia b le , len g th y and c o s tly . h e c h ie f iin a of in v ^ tlg a tlo n hs been a continua tio n of t t a Aork o r tha o l e c t l s r d i s t i l l a t i o n of m ineral o i l s Aitr. th*i o b je c t of is o l a ti n g the substenc&a respon- lb la fo r th e ir carcin o g en ic a c t i v i t i e s . Animal ex p eri ments itn f r a c tio n a l d i e t l l l a t e e fro * a Venezuelan o i l are in p ro g ress, fra c tio n obtained by m oleculer d is tilla tio n of a cerclnogenio ahele o il huve bean eubjacted to chrom atographic a b so rp tio n and two a p p a re n tly ouro hydrocarbon* have bean 1 d a te d in sn a il quantity} thaea are being in v estig ated eh caically . Painting experim ents with f ra c tio n s obtained by th is method have shown th a t many o f th e* a re h ig h ly to x ic f o r n ic e . lo n e o f th e subetanoea so f c r te s te d has been shown to possess s high cercinogenlo a c tiv ity . > few s p in d ls grad e o il* and th re e o i l s in ten d ed ss v ehicles fo r in se o tlc ld e s have been te ste d fo r oercino- g e n lc lty . A co llo id a l m aterial intended aa a p ro tectiv e against oarcinogenio o ils has been te ste d . There are indioatlona th a t i t has some p r o te c tiv e a c tio n . th e oarcinogtm lc a c t i v i t y o f two p ro d u cts formed during th e p u r if ic a tio n of c a rb o n isa tio n g as been te s te d , and found to be le a s than th a t of the averege gas ta r. 110. Ullmann, K ., Oppenheim, M. and K i l l s , J . fi. J . In d . Hygiene, 8, *88, 304 11926) th e le sio n * caused by crude petroleum e re th e s u e as those oaused by erude ooel t a r , showing the analogous substances must be p re se n t in bo th . The f in a l oroduots of d is tilla tio n are tne most activ o , e sp e o la lly 'p a ra ffin o i l . The earo in o g en lc ag en t I s p re s e n t in f r a c tio n s fre e 300*C. to 4S0*C., but i t i s n e t o e r ta in th a t th e Afxc su b stan ce causes b oth d e z s a t l t l s end e p ith e lio m a . Ill T alad e, P. Canoo r o f th e Human Lung from L u st from T arred Roade. P re e o e U e d ., 2 .1 .5 9 , 161 U l. Tan Ihmaisofee, M. JL Chmoleal Cnnoo M936) Ing. C h in ., 2^, 50-5 Mors th a n tw ioe as many aasaa o f oanoer due to so o t were found among sw eepers th en among any o th e r occupa tio n . Personal claanlineaa and clothing th a t f i t s tig h tly around tha axtrami tie s and around th e neok are th o b e s t p rev an b i.tlv ea. S im ila r c a re w ill do muoh to ward preventing cancer due to exposure to g aa o lln e tad i t s d e r iv a tiv e s , p a r a f f in s , o i l s , and g re a a s s . Such p recau tio n s a re even more necessary in cases exposed to ta r , p itc h , ro sin or a n ilin e dyes. S tr ic t medloal super v is io n and th e use o f prooesees nhioh avoid o en teet of th e w orkers w ith h a product wfljffl. f u r th e r reduce th e danger. -4 2 - - Wam3l*fi * O ccupational D iseases of the Skin (by i l 5, ' L. Schtrorz). " In d u e tria l M edicine", 1343, 317-9 Chimney sweep?' o er.cir hes been r e r o r te d in Ingland more f r ^ v c n t l y t'r.^n in j n / o th e r co u n try . I t i s s ji d . t b i t th e in r i- ir n c i vT C T .oir wrong cr.lmr.ey sweep* ia e is n t time* so re common then among th e g e n e ra l popula tio n . Cvicor of tb s i;rot*a o f chiamsy sweeps, ho'.vever, la- on th e d e c lin e in Ingl-tnd w i t i* r e s o rte d ss being preotioelly non-existent in other countries, except for an Is o la te d caee or tvo in Germany. The lo c a l i r r i t a t i o n and rubbing in o f th e so o t as th e sweep i s croupe! in descending t.he chiim sy i s sa id to be ta e o*ue. Tar ia used in b u ild in g ro ad s, in making ro o fin g n sn er and f e l t . P itc h i s used f o r making o o n d u its, le c 'ju e rsi in s u la tin g m a te ria l, g re a se s, and ?d n erd l cem ents, ar.d w orkers a t th eca occu p atio n s a re a ffe c te d w ith conedonec, timiors, w crts, k e ra to se s, and epifche- lia n a , s o s t ly o f th e scrotum . l i p , fa c e and hands. No oases o f mule epinnero* canoer h a re been re p o rte d from Prance, Germany, B u s 'if , o r Poland. The auth o r made exoarinstions o f thousands o f mule sp in n e rs eaoloyed in the United S tates and did not find any oases of so T o tal ean o er, alth o u g h th e re were many e a se s o f f o l l l - o u l i t l s and k erato ses of the th ig h s eoused by o i l - - soaked tro u se rs. X14. Wanlek, H. Melanoderma and K erato ses from th e A otign o f A sp h a lt. A rx tl. 8 * o h v e rst. Z t g ., 6., 49 (1340). In the preparation of oork p lu tes (h e a t-in su la tio n p la te o f a s o h e lt and oork) much d u st develops under ery u n fay o rab le working o o n d ltio n s . Two w orkers, who had been working f o r th re e months, su ffe re d from p ig m e n ta tio n , i n f l '.tnmatory changes and h y p e rk e ra to se s o f th e fa c e , f o r e a r m and h an d s. The h y p e r p la r tie prooeaaos mere in te n s if ie d in th e o ld e r workers* The syaotona were ag g rav a te! by l i g h t . The in te n s iv e eotlom of asp h alt dust is considered to be the oause. 118. Watson, a . 7 . Tar Cnnoer In M ice. I I I . An A pparatus f o r th e P reparation under Standard Conditions of a Highly Potent C arcinogenic Agent o f Lew T o x io ity . B r i t . J o u r. ? e r . sath., 11, 441-7 (1951) With an a d a p ta tio n o f th e a p p a ra tu s o f H-.gue and Wheeler the author has suaoeeded in making from p u rifie d tu r p e n tin e , a t *50*C., e r e l a t i v e l y n o n -to rio war whiah e l i c i t e d t u t o r s a f t e r 210 days in 90jt o f th e su rv iv o rs from * group o f 37 r^ioe; most o f th e e e grow ths *?*re m alignant. W elwnrt. Ceneer f r a r ? r a f f in Wax end M in eral 011a. r>eifena. 2 tg ., 52, ^92-3 (1935) Most chem ists rnd derm ato lo g ists b e lie v e th a t workers in p a r a f f in f a c t o r ie s G'-'t cenoar fro n th e p a r a f f in l t u e l f w^ l v _ 49- a h l a S eherber and T eu teehlaender e la ln th a t oanear Aoaa n e t eene fron p a r a if it, but fror. n ix ieral e l l a . .*, Windaus, A. ei. KewJ-akt E. Tsao D e riv a tiv e r o f 3,4-Ben>- ** pyrena. 2. Phyuiol. Chan. 849. 25$-* ( i 7 ) By oneioy tc x -ra y a ( "x-rv produce and x -r* y s ir e ot.ncer*' carcinotat*ic hydxocarbju should b t e a t e i f o r paeaible thexapeutio ra lu e j. 8u*atiT* ro m ita h a rt been o b tein ed Ith 3 ,4 - boaropyrena (X). i, le o d , F r C, The Bon-Caroinogsnio l a t u r e o f P u b ifie d M ineral O lla . J . Aa. Mttd. A s m ., 94, 1541 (1930) Ihe general e l l n l o a l tvTdence th a t th are exlata no relatio n beteeen th therapeutio uaa of reflned petroleun producta and the eoeurrenca of cancar la eoztflxBod by expe r inan ta l tudies. 10. Weed, K. B. P a ra ffin l e i ProdacVir c f , Canear, f . canear B es., J 8, 97-108 (1921) 110 *** E. B. Sein lesio n a Anong Tar toxicara, f . Canear l o a ; . JS, 4-9 (1919) * D ifferen t typ es and oonpoaltian o f ta r a ara ila , eaaaed. Only t a r obtainod fron th d ia te , o f aoel e t ] ta rp a . oontaina a sbatenos oarainecan&a to #a rte l lab w in ala Mortasa Handling c o ti t a r tweed t a r e r ta ae a ro s a lt , b at no o th er affaat Bo I r r l t a s t aotion o th e hunan bin ana fotmd f h t lo te n ; d is tilla te ta r or fron petroloum tar * UU Woodh tuao, D. 1 . C aroiaoceniolty o f Bynthetle L abria tin e O lla. J . Znat P et. Tech., Q 1087-43 (1094) ltt T--agi os and I ehi Mar e . Experimental Study of o f C a r s l m . f . Conaer l a a . , m , 1-11 . ln 1919 predaaad sanear by the experimental m U t f W i i of ta r te th acr ef laboretory asinai. *V / A