Document GmpxO9XBKyzJ7RZBo8MbrqMqm

Castleman File: American Petroleum Institute w/c = with cover letter or memo If DATE = 0, undated CD-ROM Document #:API [q DATE published article from trade journal published advertisements newspaper article published government report government inspection results unpublished or internal report unpublished presentation from conference letter memorandum industry warning labels industry sales literature industry recommended practices meeting minutes (with attachments) membership list BC notes fa ff*-+ fi* tf^r*//*** Sjjr b~ (*fvUMS^/!' &J- *-**y T&J CARCIN00H7ICITT Of BITUftWOCS COlffOUHDS *# UtmtttM BTl*V April 30, W5, ^ YmBbImI ft IhutiI Dirltloa fh Tent Oenpotj Mm Tom 01tf t In Tiew of tho insenao nouat of pnbliahed infosnatlon on Yarioua phaaea of tho aoaoar probloa it ahould bo wphaalxed that thla literature review fivea only a rapid aurrey of derelopnanta in tho fiold of aanoor roaoarah aa applied dirootly to tho petroleum, eoal tar, oil ahale and alliod induatriea. Ihilo it la far from beinf ooaploto, yot it la baliOTod that oat of tho laportant work in thla particular fiold haa boon oororod, olthor in tho roport ltaolf or in ono of tho bibliographical referonooa ciTon in tho appendix and roforrod to at tho botton of paf ! M. P. SOM THX CAHClNOOiXlCITr 07 BITUMUICUS C0MP00106 It has long bate rooo*nlxad that tha lneldamos of afclm oaae*r ! greater among aorkara la oortain industries and osovpa- tloaa than aaoag tha popfelatloa as a ahola. Attention ana first directed la 177 to tha rar? high daath rata resulting froa sarctal #seer of ohlaner swoonsi it la eight timeo *ora ooflaom la thaaa vtrfcara than In tha tenoral public In feglamd, ad lm tho United! State* tha ratio of aaaaar aasaa Ib aUaiay sweeps to doable that af tha canoral peyalatlaa?** Zb fitattaallr all aaaoa 1% to tha arotaa that la attacked! this, la alas tha alts la Mia spiamam' aaaaar dlssasssd lotor. Rifkava la sthar industries await lati _ direst eoataet with t*ra, pitches, ahala alia# ate* lifcaoiae atw a hlh lBaldaaaa of ahAa aaair( ftv tna^la, IBoma It ylaatf Wtla biiauettas, tar roaflaf, wood preooreatlTBO, artlfld pi, Insulating eeapeaads, ahala padula, ata* fp la spite af tha mopitlaa af tha Twsa^aaam kho aaaoa af ddhaalli^ H mot matll ro&mtlTelr 1*U *rt lm laboratory amiaalo by liMl appllostlsa '' *'*' * ''/ V- . f aasoapllahed hr %' data la ayfatalatif aai ttcalarly rtlTWtUt IrtHHllMI vatlaaa af this wort, aaa hafaaaaaaa #*lft -Ma^^ H-n, 31-34# 74# b 71 particularly th**ei of tho Vatlomal Oaaeer Imotltato MVirlti dpf . r -r- - .'?ijk?*' H  .*--**( -2- which 1A9 are rs orted to ts cnrclEoganic41. L. F. Flaaer fUi04rl28 our knowledge in thin field aa follows341 Aa judged b7 ell ^>llnble data for the production of akin and auboutasaoua tuaora in rata and alee, metbyloholmthrene probably is tbs coat potent of the known ohemioal circinoeens. Systematic studies of synthetic Bodel compounds hare shows that*.the methyl group is of no importance to the functioning of the oompound) that much, if not all of the efficeoy of cholanthrene is . -retained in the analogous hydrocarbon 5.10-dinethyl- 1 2 benzanthraoena; and that tha moat algnifleant atruotnrai feetore of eholenthrene or methylsholenthreme la tha 1,2-banzanthraaana ring system with a certon substituent at the meso position 10* Jh-rllethyl-1,2bensanthraosns avokes sareamas in miss nearly as rapidly as nethylaholanthrane, and, though it la distinctly less effectIts in the production of skin cancer, the substance constitutes the nearest approesh in a simple model compound to eiauletion of the biological prop erties of the hydrocarbon of more complicated structure* "All tvelwe possible moncmstbyl deriTatiwee of tha 1meetiTa 1,2-banxanthraaeno hare baas synthesised end tested . for sarelnogsmie activity, and of those the 10-icoacr is 1 the most potsot. The meeo-subetltuted 9-methyl compound stands next in order of potency, followed closely by the 5-methyl icrlvatlve, obieh produced saroomas in mite with a latent period ebout twice ea long as that observed with 10-otthyl-l2-bcmsanthretam* Methyloholanthrees and benzpyrens oaa be regarded ss 1.2-beasanthreecneo substltuted at tha mesa positions 10 and 9, respectively, and la aodsl ssmpougds the sowhlnatlon of the two typos of substitution is partisolarly favorable* h>alO-Dimethyl1.2-boBaaathreesme produced akim burners la mis# with remarkable rapidity and la this test surpasses methylcholanthrene in speed of action, though it is less effective when administered by subcutaneous injection* The thiophene lsdscue of the hydrocarbon has comparable properties*" numerous attempts have beam made to isolate the definite carcinogenic compounds la coal tar by means of distillation, eolvant extraction, etc.73, but Chile very potent fractions have beam obtained, the individual eocqpounds have been difficult to separate# Zensavay aad Higar 16 proved the carcinogenicity of 1,2,5,6-4i- peazanthraoene, the first purs oaroinogenio hydoroarbon known* Cook, Sieger and Hewitt ^in 1933 Isolated 1,ft-benspyrene, 4,5-bens- pyrene and 1,2-benzanthraoene and estlnated that the orlclnal eoal tar pitah contained not leas than 0*009)1 of the potent 1,2-beas- pyrene. Several investigator! 22, 24, 25 have attempted to eor- relate earolnogenesis with fluoreseenoe. For exaaple, the eaaeer- produolng wsterlal formed by the aetloa of AlClg on tetrahydro- aaphthalene shows a blue-violet fluorescence, shovlac three hands* 4000, 4180 and 4400 A.U., *leh are similar to the flaoreseenee If y spectrum of 1,1-bcnsaathraoeae . leaasway and Hioger nyiit the possibility of the use of the fluoreseenee epeetram for the preliminary examination of notarials suspected of beiac eareiaoceale. An lnportant feet brought out by several investigators is that the temperature to whioh a tar, shale oil or petroleum oil has been subjected determines its earelaogenie activity* la general, it would seem that temperatures up to 500*0* are without - effect ** but above that temperature carcinogens are formed, the ssTlman yield lying between 800 and 800*0* Tar and eiteh from gas works are far mere active than that from coke evens *, accounting for f0% of all eases of tar cancer in the Baited States while the coke eves product causes only 50 While petroleum residues resulting from moderate heat treatment are inactive yet by paseiag an inactive California petroleum through a tube at 880*0. Keaaawmy and Lelteh obtained a very active carcinogen 99* 90 Ivan am inactive medicinal paraffin 11 heated to 580*C. under 50 aims, pressure acquired sene careiaogeaie *0*1*1 ty 101 . Koanawey w likewise obtained an active notarial by Posing laoprene through a tube filled with Hg and heated to S1C0C. astoon 115 aohleved duller reaulta with turpentine at 05OC. Aoetylene yielde an aotivs produet ou being paaeed through a red hot tube w but it euet be pointed out that treatuent with A1C13 at room temperature alee produeee an aetlve compound 61. On the other hand, emthetle produced hy AICI3 polymerisation at temperatures up te 180G. were entirely inactive It ia suggested that the eondeneation product# of aaatylana are of e more oonplloated naturo and probably sore unaaturatad then thoee obtained from ethylene. The eereinogenio eotlvity of tore dopoade apparently not only on the temperatures of thalr fomatlon but alee an the ohcnleal anpound uaed aa the baa# steak Par example, a tar mada from plaaae at 350C. waa far mart active than one from turpentine made lmilarly, the relative poteneleo being lOOtlt. Pinene tare made at 500, 600, 750, 050 and 950C. had relative potenelee of 0, 11, 14, 100 and 54. Oxidation of n aynthotle tar at 1000. reduced ita potency from 100 to 55, end at 150-1500. ita potency fell to 0. Oxidation with an aoetaaa solution of QtoO* reduoed the potency to 14; with pyridine ae a aolvant, almost to 0. The aotlva oonatitueats of ynthatlo tars form oryatallino plaratoa. the renal slag filtrate baing almost Inactive, and the pidrato extremely potent. Shale oil la eareiaegenie, probably aa a result of the high temperatures to whish oil shale is subjected Bowever, temperatures below 400C. give a relatively inactive protect, 000C and above being required 101 . 5- Xa England where high temperature tar it used la gnatta manufacture, there ara many eaaas of slcla oanoar among iDt workman, whioh la not the oaaa in 7raaoa where the low ^aparetitra product la used. The greatest amount of Investigation of any typa of occupational oanoar has boon oarriad out on fpjnwwrs oanoar la tha ootton nilla of Lanoashlae, Sngland* Southan and Wllaon 88 la 19S2 first oallad attantion to tha axoessive oaeuxranaa of oanoar In aula aplnnars. Vonan workars ara not affsotad and about 70i of all oanoar amoignule aplnnars Is of tha ssrotum 84, apparently \l dua to tha foot that a anla spinnar at work walks to and fra in front of his oaohlne, loaning orar tha moving frana fron tina to tina to join up brokan ands of tha yarn* Tha basa of tha frana Is on level with tha groin and tha spindlas on tha frana as thay rapidly revolve throw off oil from thair bearings onto tha alothaa* In tha hot mills tha nan par spire freely and so wash off tha natural grease of tha skin, thus allowing tha oil closer oontaet . I Irritation by tha trousers and oraralls also helps tha prooess* It i is interesting to note that no trouble of this sort was noticed in Sngland until mineral oil replaoad animal and vegetable oils as a iubrloant . Henry 43 estimates that O.SSJl of all ootton mule spinners in Sngland suffer fron serotal oanoar* On tha other hand in tha United States during 19S4, for example, there ware only SS deaths from oanoar of tha aorotun, of whioh only three of tha vletlma were textile workars and three were mule spinners} four of tha six ero born In England and tha other two in Canada 45 , whioh tends to show that mule spinnar oanoar la rarely oontraoted in tha United states* In a woolen mill in tha United States employing about S00 mule fpinner3 no oaaes of aorotal oanoer wore found Sinoo the uotbod of operating this equipment i the sane in both oountrisa this strik ing oontrast ia attributed by Hamilton ^ to the t*ot that Joottiah ibftl* oil 13 used in the lanoashlre milla. However, the literature ia aot entirely clear aa to the origin and tP* of the oil need in ^gnoaahlre in mule spinning Leitoh 70 bring* out a faot of poaaible elgnlfieanoe, to the effeot that oanoer la not mown in woolen spinning ^n. avec though the sane machines are used aa in the attorn faotor lea, but points out that the room teaperaturee in the eottoa mills are auoh highor, possibly resulting in aftre relaxation of the tiaauea of the scrotum and permitting entry of oil into the eebeoeous folliolea. Brookbank Id , however, etatee that la the woolen industry pieoing of broken and* of yarn ia done with both hand# with a forward level banding movement of the body end thus there la not the esse friotion of the olothes on the scrotum aa in the cotton mills. Re admits, however, that the earns oil is used in both types of mills. A* a result of the preliminary investigation of Southern and v.ilson mentioned above, the Manchester Canoer Commission, oonaistlng of more than fifty members, mas organised ia 19S5 under the direction of Dr. C. C. Twort to investigate the mineral oils used in Manchester ootton mills. Lubrioating oila from the various fields throughout tbs world were found to have widely varying degrees of activity. A sample of Yenemuala oil was very potent while Ruselam and V*P1samples were on an average less than one-tenth as active. Purified ftadflajay had no oaroinogmnio properties and several saponifiable oils, auoh ee sperm, olive, rape, oottoneeed and naatafoot oil, failed to produoo tumors whan applied to mloe. 7 9fa under the most severe experimental ooeditions. In gtnarsl term** toe aore eetureted were the constituent hydrocarbons of the lubricating oil, the less oapable were they of inducing aaiioer in experimental animals, the physioal oharaoterietloe being the same 101 This preliminary report was oritioised savory in an editorial in the "Petroleum Times" of London *9 in that while serious oil oompanies (Anglo*American, inglo-Fersian and 3fcellhex) had contributed hi,000 for two years for the eupport of this invastigallon, yet the Manoheeter Saaoer Commission had not etsiled itself of the aervlose tad advice of experts from the oil industry rslative to the ohareoterietioe end methods of treat ment of petroleum oils* The Institute of Petroleum Technologists, while making no definite orltioiams at this time of the work of the oomiaeion, formed a committee of its own to follow olhsely the work in progress W. In 1934 Dr. A. X. Dunstan, Dr. 7. H. Corner and tir. James Kewley of the Institute of Petroleum Technologists are shown as members of the Uanoheeter Commission 81 . In 1933, Twort and Lyth of the Ueneheater Senear Committee reported that by means of solvents. extraots wars obtained of high refraotivity and oorrsspondingly high oaroino- genioity. Their reooomendations for the seleotion of an oil of low oaroinogenioity were as follows: ^hen selecting from several mineral oila with similar gravity, epeoify that with the lowest refractive index; when scleoting from those with similar refractive index, epeoify that; with the highest gravity; when selecting from those with similar refraotivity, epeoify that with the highest viscosity; and when fro* origin alone, ohooae in the following orders gussion, Pennsylvanian, Texas, xidcontinsnt, Mexican, Californian, p^riian, Runania, Borneo, Venezuela* shale. However, it should bo enphaelzed at this point that these authors state definitely thst "adequate peffMas of any of ^e oils handled, of no matter whet origin, results is a produot .................. ..possessi.ng only a eery low oaroinogenleity" 104 Also, that a sinsle extraotlon of an unrefined distillate with S0g may profoundly lower the aotivity of a previously eery dangerous oil, whilo a seoond extraotlon may render it almost in*rt. They state ^ that "it la probably eommeroially feasible to treat oils of any k origin, or oils of any degree of eareinogenlo activity, so that they asy be less dangerous than even the very best of the straight oils aoed today"* They evidently assume that untreated textile oils are used in the Laneashlre mills. Lyth of ths Commission further statsd 7i that when the rsfreotlvltr* of en oil wes lose than 0.5500 it was found to bs nontoxie, while tfh*n the value was greater than 0*5400, the oil wes ' highly toxie* Pennsylvania* oila and certain Mildly treated olla were an exception* The losina iu of an oil aeama to afford an indloatlon of its toxlolty, providing the oil haa not bean treated tad again the higher tha valua, tha more potent tne oil* The toxlolty iaoreeeea in the seme order ee iodine velue, expept for Pennsylvanian olla whloh again eooupy too high n poeltiom* The pemangaaete valuee ere not regarded ae of any valua in ooaneetioa I with aatimatlag the toxlolty of oila* (Ksfraotiwity* E*i j A 6 bn ufl>*< that extraction with alcohols, tottooc, sto., oly *iii acid treatment, loads to rf raouctlo;; in ihe potanoy, aspciftlly in the oase of the core potent olio but a corresponding r#duotlon in the rel'r activity does not always occur. Ahere a narked rduutlon in the refractivity does ooour, there is, without exoeptloa, narked deorease in oaroinogenioity; with a narked laorease in refrsotivity, a corresponding increase in potenoy. there the refraetlvlty is not nuch altered, the potency nay or nay not he affeoted and further tests are neoassexy. type. In spite of the apparent definite findings and reconnenda- tions oi the Manchester Canoer Coasission, the Caneer Research Connittee of the Institute of Petroleum Technologists 51 was not convinced that "the so-called inoldenoe of oanoer is in any shape or fora connected with the use of spinale oils", ho elaboration of this statenant was given, but was possibly based on refined oils only being used as textile lubrloants. An editorial in the "Petroleum Tinea" of London in 1637 onoe again attacked the ooneluslona of tht Manchester Committee, pointing out that only one oil froa eaoh of a number of eountrles 5 was examined . -10 In 1937 the Federation of Master Ootton Spinners doolation sent oat letter to lie member* reoouraendlng that ^jjfO purohasing spindle oils a guarantee should be obtained g,st the oil conforms to the apeclfloatlons of the Manoheater Caoeer Commission, and that teate bad ahearn that many of the oils 1b use at that tine conformed to the speolfleatlon. While throughout the reported oork of the Maaehester Cancer Co0alaaion It la stated repeatedly that aold or solvent treatment of , potent oil greatly re duoea or eliminates its aotivlty 99 109* 11, yet In 1939 Teort and Lyth Investigated aeid and slay treated distillates from a Borneo ell and found them to be aetlve, the aaxi- - * - - . -- < +< m*- gm potency being at a vlseedlty of 100-380 ep at 1S0* Molecular distillation gave a greater_eoneentratIon of the eereenegenle material than was obtained by ordinary distillation at from 3-10 am. In _ - --*. ---------------- os^lrmstloa of prsvions findings ths middls freotloas of this Borneo oil were moetly responsible for pathological changes In the organs* a oarelnogenle shale oil was separated by moleenlsr dis tillation Into frsstlonn efeleh were snbjested te ebromatographis adsorption* Two apparently pure hydrocarbons have been isolated and are being Investigated A recent report (1941) by 0. 0* Teort of tbo Maaohoster Canear Commission 109 states that feta ara variable, lengthy and aoatly and that n more reliable estimate of the aarolaogomlalty of olla oan bo obtalnod from the rofraotlvo Index and vlsooslty. (Tat the data on which selection of these two properties was baaed ears obtained by naans of this variable akin tost.) loodhouso of the Birmingham Censer Besearch Laboratory also states that mouse tests to datormina oarolaofamltlty are difficult -11- t0 correlate with human tendencies to oanoer unless these animal 1 >1 Mfta ara strongly positive or negative *' Jar example, two oila tatted (a) from a apinnin_: mill where no oaaea of mule aplnnera 0gnear bad bean recorded, and (b) from a mill where alx oanoers bad recently been reported, kouae teata indicated alight carcinogenic prop**1*** ia th of ^.e oil* but a greater action on mice 0f (a) than (b) . Dr. S. M. Brookbenk, ohairman of the Mencheater Cancer Cflg*i*iion, hea briefly sunnarized the Investigations of the CoobIssIob a reeent publication He liata the hygienic precautions to be xaroiaed in mule apianlng and urgea the adoption of the oil speoifi- oatloa given previously by Twort. Re alao makes thin interesting generalization: "Aa r general rule an oil that ia atrongly darmatitle ill not be strongly earolnogenlo and vioe versa". This ia also aeitionad by Kennaway who states that oyolohexena (which is nem- earelnogenio) ia extremely irritating to the akin and should pro duct oanoer if ohronio ltrltatiom were an eatential faetor la oaroino- ganssls. Aa mentioned previously, ahale oila are very oerolnogenio and in the Senttish ahale industry the oese lnoidenee of skin oanoer ia about 0.1% per annum among the ell workers but 0.0% among the paraffin workers M (this ia baaed on e 28 year record). This activity of doraffin la restricted by Schwarz end Tullpan 64 to the crude produot, the rwfined wax being inaotive, which view ia supported by tood who states thet the eotive components are present on!y in the orude paraffin oils. \ n/| with regard to the refining of petroleun oila. Rood * aada an lnveatlgatlon of refineries in Pennsylvania and found no aerotal oanoer, which waa oonfirmed by Haller 4*. However, Heller IS- fsmnd evidence of oaroinogenlo oompounda in Mid-Continent oil* ui refined in plant* in Ohio and Indiana* Hera oil boil* are fairly aemmon and in son* aso* load to akin oanoor* In on* oaao a nara-f- n pressman in th* Kiddle Woat wee treated for "wax boil*" for thr* year* when a oanoorou* growth developed on tho right foroar tad vas removed, but olght years lator a aoooad similar growth in tba aam* plao* had zo b* removed. Hollar ala* foand rooorda of oaaos of skin oanoor in anothor refinery, using orud* from tho Lima fiold; tight oaaos had eourred in this rofinory and ono was fatal* All of thosa oanoor* wore prooodod by warts* The length of exposure before aalignanoy appeared varied from four to thirty four years* Tbs part most often affootod was the sorotun and all but one man worked in the paraffin department* These oases were oauaod by un refined oils and Hamilton states that so far there is no proof of the oeeurrenee of akin oanoor in the U*S* from tho use of re fined lubrioating and spindle oils which have been aoid-treated* AO Heller believes that the relative freedom from occu pational oanoor in the U*S* la due to the mechanization of industrial processes, preventing direct oontaot with the pltoh and bar; the extensive employment of negroes, who are apparently less subject to skin Irritants than whites; th* use of refined lubricants from erodes whlsh are poor in oarslnogenlo properties, and the use of ter from ooke-ovens Instead of from gas works* Phillips 77 reports the particulars of a study oarried out by the U* 3. Public Health Service as to th* lnoldonoe of ooou- patlonal oanoor in Texas* Th* records of 1190 individuals having mloroseopieally verified skin oanoors ware analyzed, covering the period 1930 to 1940. The occupation of the largest group of these * -13 patients was outdoor work (faming and ranching); tfca work of *ottsewif oom oaxt in order, followad by various activities requiring aoderate outdoor life. The professions wart nsxt, follo**d by laborers and oarpantara. The railroad and patroleun Industriea furnished faw cutaneous cancers. Oafafar and Sltgrssvss in a U.S. Publio Health raport iaauad in 1940 S7 analyse 70 eaaaa of oanaar reoorded for tha aala paabars of the siok benefit plan of an oil wfiniitw oaapany during the period 1933h36; there ware 46 deaths. Tha death rate was 0.76 per 1000 and a frequency of l.S par 1000 (all U.S. death rata 0.96 per 1000) Almost 70% of the deaths were related to tha digestive systea and tha rate for this site was higher than in the tool population. Deaths free aaaoer of the gonlto-urinary systen ass 6.9)1 of tha total, compered to 15.0 in the ease at the total papulation. In 1934 Campbell 41 nade laboratory tosts oa aloe with dust obtained from tarred roads. This dust caused warts anil aaaoer of the skin and in six Months 64 out of 69 aioe showed typical tar warts, half of which developed malignanoy. This finding was confirmed by Zling, Sansonow and Haros, who also spparated a substance containing the bensopyrene naolaus fran the tar. However, Hogouneg 47 is doubtful of the danger from road tar since it usually takes years of direst ooataet of seal ter to the akin to produce skin eanser. (Teutsehlaeader *1 calls attention to the fact that alsMSt all industrial oaaeers require an exposure of about ten years before growth appears, although a fow cases nay arise nuoh later). Talade 111 likewise is of the opinion that while prl- aary lung bawri can be induoed in nice painted with tar or exposed -14- to inhalstion of dust froa tar roads, yet these rasuits oannot bo & to huaaAS* Animals other than aloo should bo aaployed #xprienta and an inquiry should bo oarrlod out on workers ex posed daily to suoh dusts. While tho aanufaoturo of briquottos In Kagland is attondod vy a high oanoor rate, 68 sines hlgh-teaperature tor is us ad, yot in the few plants la tho U.3. asking briquottos oanoor is ontiroly cbsont, partly duo to tho look of oontast with tho blador slaoo tho process bar* is ontiroly aoohanizod and partly duo to tho uso of pstrolsua asphalt as a bindor, ** This finding was ooafiraod by i an vood in his investigation of briqaotta aanufaoturo in Pennsylvania. Ho addition of glyooridos 89 rodnoos tho oaroinogonio potanoy of ainoral oils but not to as groat an oxtoat as lanolin, gpaakmaa and Chaabarlain 89 stata that ohila alsohols hartnot boon uJtd for this purposa tharo oan ba littlo doubt that suoh polar ooapounds will raduoa tho risk of oanoor foraation by promoting ulalfioation, sinoa an oil whioh is sasily and ooaplotoly removed from tha skin aust carry lass risk than oaa whioh is diffioalt to aulsify. Thaso investigators also boliovo that polor ooapounds in a mixturo with ainsral oil any, howovar, funstic* in yot nnofeor way. It is known that tho oaroinogonio agonta of ainaral oil *ien assoolatod with unaaturatod ooapounds aro froo to oonoontrats at any surfaoo to Whioh tho oil is applied, tho noa-polar paraffla aoloouloo offer ing littlo ar no realstanoe. however, whan oil-aolubla polar ooa pounds, suoh as olayl aleohol or wool-fat athar, ara aixod with ainaral oil thoy oonoontrats at tho surfnoo, excluding tho loss polar oaroinogonio hydrocarbons -15Se.ueir'v'*^ stresses the neoesalty of absolute cleanliness of body Md clothing, the application of castor oll&$ to acposod jurf^ces md medical inspection every three months. Brookbankl5 figgeat* a aikture of lanolin and nilvs oil ba applied to tha akin* DuaVha* advooatea tha uaa of an oil-solvent cleanser oisllar to tha ether aoap uaad in hoanltala In ordar to reaove all of tba lubricant from tha norea?. Xn view of tha suggested uaa of lanolin tha following onould ba of partiaular lntaraats Dr. JU -Cevdry, of tha fashlngton University Sehool of Medielnt, St. Louis, haa Just aanounaad (H. T. Harald Trlbuna April 29, 1945) that aalla ean ba sanaltlsad to bscene eanoar oalla by treating than with a aubatana# ahlah doaa not oauaa aaaaar and whleh will araa prevent powerful #*ncsr-produoiag ohenloals fro* exhibiting that property. For example, whan tha p--atful carcinogen aatfeylabolenthrone la alxad with lanolin It la without nation whan appliadtta tha akin *w of nloe, although alone it alwaye raaulta la oanaar. However, whan thaaa nlea ware than treated with aathylaholaathrene In banaaaa they developed eanaara worn gulafcly and tunors of greater virility than n&aa whloh had not ran*lved tha eeneer-prrvanting treatiMtfty^ VB-TL DS . -Id* Rif* ARAM C125 1. Anon., Cancer froa Spindle Oil. oil and Color Trade* Jhly 2, 1957, 3. A latter cent out bj the Central Conr-lttee of the Federation of Hester Cotton Spinners* Association reoosneads that when purchasing anIndie oil aenbera should obtain e guarantee that the oil conform* to a specification of the Haneheater Cancer Committee which recently issued a formula elalaed to nlnlmixe the so* tailed oanecr-produelng eltaunts of mineral oil. Tests showed that acny of the oils in use at present conform to this specification and are obtained at regular prioes. 2. Anon.. Cancer and Klneral Oils* Oil and Color Trades J., 102. d*5 (1942) The report of the Ihnehester Ceamittee on Cancer. Issued for the year ended October, 1941. states that in efforts to isolate end eharaeterlse individual carcinogenic hydrocarbon* from shale oil. recently appreciable quantities of sryotallino neierlal bam f been obtained, but it la too oarly to diaonaa reoalto * la detail. An far ae eea bo Judged, all fractions * ' obtained frost snssusisn Oil by chmantogrephls ad* sorption are active. Proprietary eollolda here varying effeota, depending on tbs conditions of the experiment. A colloid containing a eblor-eonpouad nos found lens sffloasloua than an oIIts oil-lanolins nixturs as protection against the eerelnogcale action of shale oil, while the rarer** appeared to ho the ease Oban the carcinogenic agent used was bcmxpyrcne. 3. Anon., The Problem of Cesser. Petroleum Times, 99, )JO U930) () The foilswing appeared in a resent Issue sf the British sdlssl Journal in eoatncation with the mac of mineral luhrlsating oils la the Lancashire sotton nlllsi "The lamehaster Osnssr Csnmittes, chile studying the pert played la the productlan of aallgnamt growths by the lubricating oils used in cotton nllle, has obtained lafemetlorn about the osreiaogsnotle power of various olio and the oomeantratlom within them of s sensorproducing principle. Xm the course of this roeearah, two pure eempounds of loocn chcnical ccaspositlen ham been proved capable of produolng tuaors, and a study hcc been ande of the factors which change n nosserein* ogsnls into am sstlm ssrslnogcnis substance. Already 19- *'*e of the methods for destroying the cmeer-pr-'duclng power of oertain oils h we proved to be efftctlve, at least in part, and on# method led to the preparation of a purified oil whioh, when subjected to vigouruus test, has failed altogether to oroduee canoerous growth#. Representatives of the cotton industry, after comparing this oil with the orude untreated oil havs Said that it* lubrioating power le unimpaired, and the Manchester Committee le therefore eble to hold out the hope that before ion* It may he possible to put on the market an oil whioh fulfils the needs of industry without being a sjuroe of danger to the workers." Assuming that the uee of spindle oils hs such a source of danger, It almost neoeasarlly follows that other lubricating oils whioh come Into closer phyeleal oontaet with the worker mast he sources of higher potentiel danger than any of the light lubricating oils used in the locm* of the Lancashire cotton industry. It might be proved uoom investigates that little difficulties would present themselves in the production of s spindle oil which is nancarcinogenic, and lest the present attack widens itself to include the whole range of mineral lnbrloetlng oils, it would he edrieehle to meke em in vestigation of the most embrssing eharester. L, Anon.. A Dangerous Report on Lubricants and Cancer* Pet. Times, 22, 319-320 (1932) Criticises the report of the Manchester Cancer Cosuiilttee in that the Committee has aeoepted contri butions of 1000 for two years from the Aaglo-Ameriean, the Anglo-Perslan and the Shell Max hut has mot availed itself of the services and advice of experts from the oil industry relative to the character and methods of treatment of petrolenn oils* Manchester Committee on Caneer Report. Pet. Times, 295 (1937) The 1935-36 report of the Manchester Committee am Cancer claims that "with a knowledge of the refractive index of ea oil, and of the viscosity, one can form a more raileble estimate of its eanoer-produelng powers than by the application of the smspls to the skin." Xt is pointed out, however, that similar conclusion in the 1933-34 report was baaed on Insufficient evidence and that some dieerepeaoias with animal tests were admitted, agd that la the 1934-1935 report the animal testa were reverted to* It is also pointed out that the above conclusion was hassd on the examination of only one oil from each of a number of countries* 1 T ear -18* Occupational eanoer of the Skin. Annual Peport, Chief Inspector of Fsotoriaa and >vork:ho:>s, Year 1937 A table shoeing distribution of epltheliomatous ulceration by Industry for each of the years 1933-107 la given In an abstract In American Journal of Cancer, 34. 613 (Deo. 1938). Tar distilling and ootton ule spinning taka tha greatest toll. The increased 1937 figures for tar distilling cases la attributable to voluntary periodical examination In some plants. ' Alaoy, H. Cancer Prophylaxis by Preliminary Treatment with Carcinogenic Polycyclic Hydrocarbons. Z. Krebs* foraoh. 3, 32-9 <193) Vioe and rats were treated with wary small doses of 3 carelnogenlc hydroeerbons (benxo-pyrene, methloholenthrene and l,?,5,6-dlbcnxanthraeene a method of protection against the implantation later of highly virulent tumors. Usually a single sub cutaneous injeetion was made of the earelnogmiie agent dissolved in sesame oil. Tbs asst efficient dose in alee was 1.5-3y and the most favorable time 40-70 days before the Implantation of the tumor emulsion. Oibensanthraeene wee somewhat the most effestive. Tbs protection la nice wns only slight. Development of the tumor mas delayed 5-6 days end for 5-6 days was slow. Growth than bsemes rapid and on the 17th or 16th day after Implantation of the turner the tumors were of the seme alee in the animals with treatment mi the control animals. Me hindrance to tumor growth was obtained in rets given l-100y doses, occasionally 150-lSOy doses 3-4-60 deft before im plantation of the tumor. A definite active protection cannot be obtained by this method. Bachmans, S. at si. Production of Csnoer hr Pare Hydroeerbons. Proe. Boy. Bos.^B123f 345-66 (1937) With respect to high carcinogenic pet may methyleholcnthrmxe *Is not surpassed by any eoapound yst tested, although it is almost spmsled by sholsnthrens. Production of carcinoma is . favored by imtroduetion of eubstitumits into the 5 pooltlam of the 1,2-bcmaamthreecmc msl.t 6-Ms-3 4-bemsophemamthreme le earelmogMle te a high degree aa are eertala hcoceeyellc fcydroeerbcme derived from the pcmtaeyelle hydrocarbon 3,4-bemsepyreme. It Badger, 0. fc. et al. Production of Canoer by Pura Hydrocarbons* Proo. Roy.'Scq. B129. 439-67 (1940) Information as tc the most effectual method for the production of any particular tumor (pair.tin/r, sub cutaneous injeotion. feeding) ie not decisive} in the two latter the fur la always contaminated, and inhalation and swallowing oennot be excluded by. any of the methodii. The 3,4-benzophenanthrene compounds poetess enrolnogsnlc properties, and apnarantly art sore active than the benzanthraocnee In the production of Miltitle tumors, oholangioaa, and tumors of the lungf the 1,2-substttuted eoapounda are more aetire with respect to gastric tumors. Compounds substituted on the l,?-elde are ueu&lly rore carclnogenio than those substituted on the 6,7,6-alde. Among the 1,2-benzanthraoeaes, ths 5-n-Bu, 5-b-Ab, and 5-n-hexyl resemble the 3,4-benzophenanthrenes in their aasoelation with e higher incidence of lung adenomas and sniltlple tumors, and a defioienoy la earoome production. Badger, 0. X. et al. Production of Cancer by Pure Hydrocarbons Pros. Roy. Soc. Bill. 170-62 (194?) In the series of 5-alkyl derivative* of 1,2-benzanthra- osne (Xe, Et, Pr, iso-Pr, Bu, CjHji, C^c) the higher members showed progress!?* diminution of carcino genic power on the skin} member with more than 3 C atoms in the side chain did not produoe asreoma. With der ivatives of 3,4-benzophenanthrene, substitution In position 7 and, to a leaser extent, in position 1, promoted carcinogenic motion; most of these compounds ware defUo&tent in power to produoe agrooms. 1.2.3*4-Tetrarethylphen5nthrene had a sight but distinct ability to produoe akin tumors, 3,1,5,6-Dlbenzofluorene had no notion on the akin and thereby differed from the 1,2,3,4-, 1,?36-, and 1,2,7, 8-oorpcunds. 1,2,$,6-Blbenzooarbazole exhibited a slight tendency to produce tumors of the llrer. While multiple tumor? could not be ascribed with oertainty to the action of the sddnisttred compounds, the moat striking cases of multiplicity occurred under the influence of 2,?,/.- Fubrtituted -)hen :nthreoei-, 1,2,5,6-dibenzocarb:z . le lud 1,2- 5,6- d 1b er.c c ri d i n e. 11. Earry, G. et atl. Production of C-ncer by Purs Hydrocarbons. Proc. Roy. Soc. B117. 319-51 (1935) A large number of oompounds, ohlefly tetrscycllc '-nd pentncvollo srorstic hydrocarbons, were tested for canccr-produoinv action, \flth cios as exparimental animals. Considerable canoer-^rodueing t'ower was possessed by 1.2-benzopyrene (fror coal-tar pitch), methyloholanthrene (a deriv. of deoxyoholic acid of bile) and 3,4-banzophenantbrene. In order to be carcinogenic, derlvs. cf 1.2-benzanthrecene must contain substituents in ooritlons 5 and 6. -20- 1* Berwnann, P. Veohanlss rf Tumor Production by Chemical Admits. Canocr Re^csroh, 2j 660. (1942) Tha following principles for tumor production by chemical a*anta arc hypothetically established* 1. The form and size of a oarcinogauic hydrocarbon and of its related heteroeyolie compounds determine its activity. Jfvery substance which imitates more or less oloscly a siren parent structure resembles it also la its blastomatogeulc action* 2* In the Urine coll, the oaroinogcas arc adsorbed by an acceptor possessing s definite adsorption area* This sets an up^er limit for the dimensions of the aotlre compounds* A lower limit is given by a decrease la adsorbeblllty with decreasing else of the molecule* 3* All carcinogens are coaoelred ce parts of an "ideal eareiaoganlc structure 4* A earelnogen can be inactivated by additions which prevent ite proper adsorption. The mechanism of thin hindering effect la discussed* 13. Bonesr, 0. M* Tumors of the Shin Produced by Blast-furnace Tar. Lancet i, 775-6 (1932) The results obtained with four samples wars remark ably similar to Bersablun's and blast furnass tai ls therefore carcinogenic, though not se potent ns the gas tar employed. The reason that it has bean iamocnous for man is that tho yield is small, and it is regarded as a waste produst and is disposed of without farther handling* U. Boyland, I* and Bruce, A* M* Oertinogcale Aotlon of Dlbemstarbazoles* Pros* Boy* Sou*, 1221. 429-41 (1957) Censer of the bladder Is unduly fresusat dpdMIlib* chaedeal workers, end these dealing with |uryirtayle+ nines and ihmoldln* seem meet liable to the 'dlees*#* It has not teen demonstrated satisfactorily that naphthylamines are eerclnogcale, and It ie possible that it is met they whith are responsible,for sender of the bladder, bat Impurities formed during their manufacture, each as Alnsphthylsrines end dlbeweer- basolas* inbstehses of tale nature were therefore tasted for snrelnegcnie activity by painting on the skin of mieo and one (which proved most active Cm mouse skin) else he subcutaneous injabtlon inks rats* The meet active was 3t4t 5l6-dlbemkeurWnole bat this was toxis. Zt produced malignant'skljfturners in nice in ISO days* Of the' ether suhstausee tested. It2t5t6-dlbcnsartamole wus carcinogenic and ltt*7l 6-diabcamearbasole feebly ee* The dinaphthylasdnea> O-aminoasotoluene, known te pieduse hepatema, ami ; dianino-esobenseme (Ayneldlse) all fUilsA to pte--SS tumors on tho skin of aloe* Opted! o-ecll wareemnte, erne of Wish mi proved trcmeplactable, owe mM in rets by subset Hsus lnjcetlcaui sf a eeU eidul saspcmslcu sf I* 4* hi Mibmmrtuli* -Sl id. Brookbank, 1. M. Muln-Spinnnr'a Caaear. Brit. Mad. J., 8tS-3 * (4.S6.41) * 14. Brookbank, I. M. Mula Spinnnra Canoor. Bpithnliona of tha Skin in Cotton Spinnnra. H. C. Lnwia and Co., Ltd., London. 34 pp. (1941) Ma firat knoun eaao of aarotal aanoar In a vulo aplnnar eraa raportad In Xanahnatnr In 1867, 87 yaars aftar tha Introduction of nlnaral lubricating ollj bafora that tlna apai* oil and naatofoot oil had baan tha principal lubricanta. It io now knoun that eanaar of tha akin, Mother of tho aorotua or olooohora, la nalo aplanaro la eanood by oarclnoftnic oompounda ahlah ara praaant in nlnaral lubrloatlnc olio though not In lubrlcanta dorlrad fron --or rogotablo oonroao. Soso nlnaral olio ara nora oarolaognalo than othara, that dorlrad froa ahala being particularly daagcmue, and It haa baan loarnod by experience that aanoar la norelllkaly to bo aaaaad if tha aana lubricant la uaad aantixeouely, than If tha kind of all employed la oeeaoloeally changed. It haa baan found alaa that by mixing anlnal or rocotabia all with nlnaral oil tha earolnogcnie potency of tho lubricant nay ba abatad. 19. Burrono, I., ftlagar, I., and t--nay, I. L. Xsperlmcmte in CaralnacMtalai tha Iffaat af tho Bnbontonoomi Mi Imtraporltonoal Injection of Lard, dire 811 and tthur fatty Material In Bata and Haa. |. Bath. Baat. 41. 418-Id (It*4) " it* Cmpball, f. A. Ikparlnnital Production of Canaar by laat Obtalnad fron tarred Boado. Brit. Mai. 1.8.14. 118-4 Thla duat aaaaad vaxta and aanoar of tha akin of nice with nataataaoa aonatlnaa in tha lMgof in i nontha B4 ont of 89 nlao Moeod typlaal tv vurta, half of Ml# dtralapod ulifMMf, _ 19. Canpball, f. A. Tha iffacta of load Boot Brood" faun for Product* Upon Ma Xnaldanaa of Primary tac Tnnora of Ml to. Brit. B. MU. Both. 11, 118-84 UfBfl. It haa bom Mom Mot duttrren tarred iciti auaaaa oaaaar of Mo akin of nloo. Bond dual aim tar* at. ranted by bantana, dona not oanao aanoar of Mo Ma of mlaai It otlanlatoo tho prodnotlon of lane tannra in nlao, but not to ao great aztant aa Men tho toy In Sanpball, I. A. Carolnagnat a Manta Praaant In tho AM and Inaldanaa of .Vrlinary tMaya in Mlaa. Brit. I. Path., M, UMI UffEil* !) Ma Sllnx haa jontlnood hla Mat mlgfeO indue# lung * Bo anoloyad -St and aeot aoreped fron exhaust pipaa of anginas burning haavy oils. lata wars exposed to thaaa duata for 10 min. an hour for 6 hre., 9 days a week for 1 yr. The death rata of both froupa waa wall within tha limit# of that for tha oontrola but tha nunbar of lung tuner# waa amia Ant hlghar. Of thoaa azpoaad to azhauat pipa soot, 89* living 10 noa. or nora daralopad tiaora. fha noat active aubatanoaa taatad waa duat fron tarrad roada. Oats am alao glvna on nioa whaaa akin waa paintad with "tar* fron thaaa aubatanoaa. H. Clark, 1. Y. Canaar fron Lubrlanting Olio. 011-Colour Tradaa J., 11.9.94, 18T0-9 t. Caok, /.V., Hawatt, C. and IIagar, X. Coal-Tar Constituents and Canaar. Vatura, 190. ttl (1998) Boraral hydrooarbona wara iaolatad froa aoal tar Ai A wara motive in produaing oanoara and whiah had tha typlaal flaoraaaaaea apaatrm of aarainagania fraotiona. Tha noat active hydrocarbon iaolatad waa 1,S-bcnzepyreac whiah produced eancar in half tha tina required by 1,1,5,4-41- baaaanthraaana. Parylana and 4,9-banaopyraaa wara aloe iaolatad. IS. Cook, J. I., at al. Production of Canaar by Para Kydroaarbana. (a) (b) Proa. Proa. toy. Boy. 8oc. Boa. (London), (London), Bill. till. 458-04 405-94 t. l9tM9f)|. t t|a) Mlao wara aaad aa azptl. animala, and a atwdy waa nada of tha action af IS different polyayalla arenatie hydraaarbona, oontg. 9-4 ringa in thalr raap. nala. anti applied inaaln. ta tha intcroaapular region, uawally twiaa weakly. Of thaaa pure canpda. only l,S,8,4-4ibaaiaa threeana and aartain aloaaly related eonpda. produced eunecrj it waa aotlTo in 9 different solvents, and waa affective Aan applied in 0.009* aaln. in CB,. Of 899 nice treated with thle aonpd., 10? developed tumora, including tt oplthalianaa and 81 papillanaa. (b) Tha investigation hea bean extended ta inalmda 88 addnl. palyayalla arenatie aonpda. Tanora wara pro duced by 4-1eoprepyl-1,8-bgnaenthraaana, 5,4-ayalapantana-1,9-bMieatbrcaano, phanamthroaaeasphthane, and 8 darira. of 1,8,9,4-dlbenaaathraaanat 8*-ha, 0*-he, - -------- 9,10 (Aei.)i. . 4, Cook, 7. V., Kawott, 0.1. and Ilager, X. fha Xaeletlan af Cunear-Prodsting Bydroearbane fran Caal far* f* Chan. 8oa., 898-408 (1989) Tha preparatleaa derived fran aoal tar pltA by a variety of aalvont artraatian nathoda, tha fraatiano aaparatad by fosnatlon af pi aretea, distillation and crystallisation, and Aa hydzoeaibeng.ll l-bnt||yne, and dtB-bansyyrana, parylana and 1,9-lnwthiiani, s have proved aarolnogcnl a and hove given Aa ayna ftaoreoinaa apaatrai (bands at 4000, 4100 and 440OA ). Tha original aoal tar piteh centalaed net less than IdMI af l,t-bASpyrane. I '**.--'V-V ~ T: Cook, 7. V. Synthaala and Biological Xffaeta of Caralnogunla *** Hydrocarbons. Chan. tad lad., w, iott-3 (1935) Cartala font* of akin aanssrana to oaanpatlon eawaaa la laduatrlaa ahara ahala oil, coal tar and lubricating oil ara employed, hare bean ahoun to be daa to the bmaanthraeeoe group of hydroaarbona *iieh aloo Impart fluores cence to the oila. The axaat nature of aaaaar foxmatian la tha htaaan body baa aot beam explained although a alaliar bensanthreoene bydroaarboa baa been found to bo produced by body ahaagaa froa aabataaeaa normally present la tha human body. y Cook, 7. V. Carainogaola lydroaarboaa and fholr lalatlonahlp to tha Itarola. Chon. Veekblad, U, 969-6 (1916) , Bariev of hletorlaal derelopnemt of recognition of tho aamear-produelng constituents of aoal tar and oarllar laTaatlgatloao} tho deralopnant of flaoroaaanaa apoetroaaopy and tha ayatoaatla atody of aymthatla sarslasgomla hydrocarbons inalndiag a Muiy of tho rooulte obtalnod from tha oxoalmatlaa of a complete aarloa of totra- and pantaayalia hydroaarbona and a nodoratoly arlda raaga of benzanthracene derlretires. The speculation la adroneod that a moao I atom in a completely aromatic atrueture playa aeoa rola In tha aaralnogania process. Tho ioola- tlon of 1, t-banaopyrana from aoal tar and lta synthesis ara raaoontad and an account la glran of tho ayallsatiian1 of blla aald derlratlrea, and tho orantaal aynthoala of nethylohslamthrcno, a aaralnogania bydroaarboa rolatod to tha atarola. Zt la lnfarrod that thara la aona aaxynle faotor praaant in tho antool body *lb lo oopablo of offaatlng dahydroganatlon of tho atarol ring ayatan and that oxoeoolro aatlrlty of thla faator nay oonooirobly aontrlbato to tho prodnotlon In tIto of aaralnogania eaepeunde. tf. Cock, 7. f, , dhanlaal awpaaada 00 fanlaagnila dganto. in. 7. Connor, B9. Ht-99 (1699) *, fall omrrayio glrcn af tho aaralnogania chemicals, daallng both rith tholr ohonlooi rolotionahlpo and tha&r blalagla offsets, bringing togathar, mndar vail dbaoan headings, all tho notorial ymbllahod up to tho and of Itid. They Inolmdo not only tho hydrosaxbono of tho bannanthraaano trya, bat alao tho aao aanpaanda, ootrlnt tho atyryl galnollno derlrstlre dlooororod by Browing at al, and tho lnorganlo unyianla alma chloride and araanla. A bibliography of 164 roforonooo lo appandad. IB* Cook, 7* V. and Kamnnony, 1. I, Chaalaal Cnnpnanda on Caralneganlo Aganta. 71rat hpplmniarf Boportt Literature of 16>f* in. 7. Csnear, J * (1910) Amthoro praaant an oAmiUto mlirof thlo aubject uhiah ahomld bo of Intaraat to all industrial phyoleiaaa. Zt aontinooa tho oarllar rorloo nod tho boo roporto Wgathar hart bibliographies totaling 9f4 rafaranaaa. -24- 19. rvls, *. Charnicl Carcinogenesis, Drugs, Dyea, comedies *.n<3 Cosaatics with Particular Reference to Bladder Tumor. J. Urol, 49, 14 (1943) Author""7i senses* at considerable length the large number and variety of proved ohMical carcinogenic agents which may be introduced into the body by ingestion, in- helation, injection or cutaneous application. He strongly inclines to the theory of some ehemioal oarcinogenic agent. Many are cited such as derivatives of ooal tar, crude mineral oils, an anllin dye "intermediate", amo dyes and estrogenio substances. The aniline bladder tumor of dye factory works develops after years of exposure to what are probably extremely small dally dosas. The theory le advanced that thsrs may be many other oarcinogenic agents as yet unknown whloh are unknowingly encountered in the routine of dally Ufa, and perhaps through the use of many drugs, patent medicines and oosmetlce, vitamins, aax hormones, and tha tremendous list of anllin dyes used in the coloring of food stuffs and fabrics. 90, Downing, J. C. Industrial Dermatoses. J. Ind. Byg., 17, 138-168 (1935) A review with <08 references. A section on chemical agents including inorganio compounds, hydrocarbons and orude eoel tar products and other orgsnlo compounds} treatment and legal aapeote. SI. Pell, A. Oil Button (flalokonlosls). Press# Med., 40, 1541-t (1932) . Description of a dermatitis in industrial workers caused by heavy mineral oils, including treatment end prophylaxis. St. Pieser, L. P. Carcinogenic Activity, Structure, and Chemloal Reactivity of Polynuelear Aromatlo Hydrocarbons. Am. J. Canoer, 34, 37-114 (1930) A long review which includesi I, a crltleal evaluation and comparison of tha methods for determining careinogsnie activity} II, Information concerning the prepara tion and purification and tha oommerelal sources of tha carolnogenle hydrocarbons} III, a summary of tha work on oorrelatlon of ohamleal structure and earelnogsnlo activity, end XT, a summery of investigations on tha metabolic fata of various active hydrocarbons. Thera is e very extensive bibliography. 33. Pieser, L. T, Production of Canoer by Polynuelear Hydro carbons. Univ. Peons. Bicentennial Conf. Causa and Growth of Canoer, 1-87 (1941) A review devoted to 1-eontainlng oeroinogans, relation of earelnogenlo hydrocarbons to the starSlda, eareinogeale activity, chan, structure and ahem, re -15- activity, nature of a possibla reaction leading to carcinogenesis and of the metabolism raaction. If carcinot?ante hydrooarbona can ba produced at times In tha body by steroid metabolism, thalr most likely precursors are among tha steroids of tha adrenal cortex. Tha Initiating action of a hydrocarbon in carcinogenesis probably involves substitution in tha hydrocarbon at its most reactive center, probably a direct Interaction of the hydrocarbon with an S-S linkage of the cell protoplasm. Metabolic elimina tion of a carcinogen probably is a detoxication pro duced by a mechanism difrerant from that laadlng to cardnogenaais, and involving a diffarent point of attack in tha mol. Tha reaction of datoxioatlon and that of oarolnoganasla ara compatitiva. Detoxication may lnvolva biol. hydroxylatlon to a phanollc deriv., or oonvarsion into dariva. of meroapturlo aeid. 34. Fiaaar, L. 7. and 71estr, M. Carcinogenic Hydrooarbona. "Organic Chemistry", 1944, 814-Id Caroinogenic aotlvlty and structure; correlation with ohamioal rcaotivity; methods of synthesizing oarelnoganie hydrocarbons. 39. flrquet, J. and Malter, M. A. Pitch Cancer ae an Occupational Disease, Archive de Madeclna Socials et d'Hygiene et Revue de Pathologic et de Physiologic du Travail, II, 797-807 (1939-40) The authors report their experiences mad# in medlaal supervision of 12$ workers in the province of Liege, working with pitoh or ter. There were found two epitheliomata only, and no lung cenoera. T. Henry made a ahamloal exmalnation of various pitches et to their content In l.C bsnzeneanthracene and 3.4 banro pyrene, (the two most effective eancarogenio eubetanees in animals) and he found In the pitch 1-8$ of the first, traces up to 0.44 in tha second. The examination of tha pitch dust in the two briquette factories revealed mostly large particles: in tha workshop 80$ of a diameter . of 30-lOOu, in the storage rooms 90$ of 80-50u. Therefore it seems--according to the authors--that irubstenoes which are eanoerogenic to animals are not for men, but more research la neoesaary, (The material is much too alight for any oonalumioas in tha opinion of tha abstractor.) 87, Oefafer, V. M. and Hltgreavea, X. Disabling Morbidity and Mortality from Cancer among Male laployaea of Oil Refin ing Com3any, with Refaranoe to Age, Site and Duration, 1933-38, inclusive. U.S. Rub. Health Ropta. 55, 161715*6 8.25.40) -16- Gugllaninetti, M. Do Meoadam Roads Produce Cancer. Bull. Acad. Med., 122, 39-94 (1999) The author firat reviews the literature. He questioned various hospitals in some of Germany's large oitlea re garding the number of observed ceaaa of cencer and sent these reports to the managers of the road building system in these cities. Increase of eanoer was affirmed but without relation to macadam roads. Hamilton, Alloe. Canoer from Tar and Fetroleum. "Industrial Poisons of U.E.", 410-9 (1928) Hamilton, Alice. "Industrial Torioology", 184, 285-4 Occupational oanesr is rere in France. In the U.s. the only published oaae up to 1990 was the caee of e man who had worked for 20 yrs. at the paraffin process in a petroleum refinery. In 1928 the Health Comittee -of the League of Rations requested its msmbsrs to aid in a world-wide inquiry Into the ooourrenoe of oeoupetional oancer by undertaking a study of tho question in their own countries. Ihe Rocke feller Foundation than nada it possibls for lure Holler to make an intsuslrs investigation in this sountry, and his report was published in 1990. Heller eonflxsed tho inpresslon held by American authorities on eanosr, that those of occupational origin ere Tory Tory raro in tho United States. He found in the reoords of tho two low . York hospitals spedallting in oanoer only 97 oasos of skin cancer that oould possibly be traced to tar and tar products, 26 of these occurring among nan handling gashouse tar or pltoh, only two in eoke-OYan tar or pitoh workers. In a Cleveland plant making oarbon and dry batteries, imported feigllah gas-house pltoh was used up to 1906, when it was supplanted by American coke-oven pitch. There were 81 oases of oanoer among tha workers in this plant, only 4 of which ware in aan handling eokooven pltoh, and theca were not considered by the physician in charge to be indubitable easea. Hartwell, J. L. Survey of Compounds which have been Tested for Carolnogeiilo Activity. U. 8. Public Health Service, 371 pp. (1941) This bulletin represents s survey of tho field of ohMleal earolnogwtsls in tho higher animalst the action of oaroinogene on Isolated tissues, tissue cultures, plants, protoaoa, and baetsria is not considered, the literature is eevered to 1989, end the eompllation also inoludea experiments with 159 compounds from tho unpub lished work of Dr. M. I. Shear and Dr.'H. L. Stewert of the latlonal Oehoer Institute. The results of the test ing of 61 of theae eompeunds are newly reported, while 46 ere new to the whole osneer literature. Altogether the work comprises data refarrlng to 696 ehcancel sub-. stsneest of those, 169 are reported to be oarelnogenlo, 27- apert from 23 observed as causing paiilomas only. After *c introductory discussion, the bulletin takas the form of a tabular review on the following classi fication (figures In parentheses show the number of entries for each oategory): A. Inorganic substances \35). B. Organic compounds: I, Aliphatic (36); II, Poiyeyclic3ioyclio (26), tricyclic (47), tetracyclic (152), pentaoyolio (114), hezacyolic and higher (25)}; III, Azo-compounds (39); IV, Steroids (86); V, Hetero cyclic (59); VI, Unclassified (77). Aithin this arrangement, eoapounds are individually numbered and then grouped aooording to prototypes and alphabetically. The tablee give structural formulae, literature references, particulars of species, strain, aaz, and number of animals uaed, preparation, dosage, and routs of administration of compounds, nature of sites of tumors lndueed, mith details of duration of exoerlment and survival rates and other remarks. Tht shove conditions show the wide range of informstion ncoessary in order to assess the oarolnoganlo aotivity of m a given compound. The author draws attention to the incompleteness of the data for many of tha compounds listed, end urges the more systmsatle Investigation of compounds already studied in e preliminary fashion, and for tha filling of large gaps maong subatenoee whioh It would seem dtslrabla to teat. The review la oomplatad by a bibliography (ovar 1200 refsreneas) and aaparats indazaa to aompounda, routes of applloatlon, vahlolss, animal spades, and tumor-sites. 4t. Halier, I. Occupational Canoars (in U.S.). J. Ind. Hyg., 12, 169-197 (1930) The ohsmloal propartlaa of gas-works, eoka-ovan, produesr-furnaee and blaat-fuzmaoa tars and pitch are briefly outlined with a view to correlating theaa pro perties te center ineidanoe among workmen In the in dustries Involved. Am a result of aztanaiva surveys and health record exurns.. gas-works tar and pltah were reeponalble for 70.2m of the oases while ooke-oven tar and pitch wore held responsible for only 5.4$. Coke-oven tar is much the less Injurious especially when cognisance is tgken of the faet that eoke-ov& tar la usad much mors extensively. The presacoe of olefins in gas-works tar seems to be of particular importance and may ba a cause of oil cancer. Occupational eanoar does not oaeur in tho bripuat afg. industry. Mineral oils vary in earcinogenie aotivity aooording to thoir olefin or uasatd. hydrocarbon contact. There la no mothod for tho dotm. of tho amt. of olefins in tho various srudo oila; if sueh a mothod axleted, it would bo possible to measure the cancer-producing power of mineral oils. Censer Is not attributable to tho oseupatiem of mule aplxraer in the U.S., possibly because of the carefully refined lubricating oils usad oa the aeehlnea, thua ansurlng relative freedom from oloflns or uasatd. hydrocarbons. I -23- i. Hry A. Stufly of fatal Cases of Canear of the Serotum. ^ J. Aa. Mei. As*n., 109. 1667 (1957) 44, Hleg*r, I. ,8peotra of Cene>r-produeing Ters and Olle and of Related Substances. Bioehec. J., 24, 505-11 (1950) **, Hoffman, f. L. Mule 8pinners Cenoar. Monthly Labor lev. of U.S., 27, 457-475 (1958) 4d# Hoffnan, V. J. Industrial Caneer. Prevent. Med., 6, 7-54 (1956) One of the seven typer of Industrial cano*r"dl ecussad Is cancer of skin in worker* exposed to eoal, tar, pitch, soot, shale, petroleum snd arsenic. They nay cause en epitheliomatous form of caneer. 47. Hogouneng, L. The Caneerigenlc Hydrocarbons from Tar and the Terrlnc of Hoads. Ann. Iyt Publ. Soelale, 57, 1-7 (1959) The eeneerigenie hydrocarbons found in ooal tar produce skin oenoer in exposed workers usually only after direot contact with the ekln for lone periods of tine. It is believed that nan la such more raaistant to the setlon of these neterlals than lab. aninals. 46. Hooper, V. C. Cenoer in Feletion to Occupation end teviromient. Bull. ha. See. Control Caner, 16, Ho. 6 \/uro, 1945) Owing to industrial development, the general popula tion end feotory workers in particular, ere ezposodto nacy new environmental factors, many of uhloh are diseese producing. Occupational oanears are eauaed by numerous ohtnieal end physical scents. Among ihm are the heavy nstale, nitrates, aromatic md.no compounds, benzol, asbestos, mineral oil, soot, radio-aetivo eubstanoea, ultraviolet radiation and X-rays. The author cites etetisties taken mainly from the records of industrial coneerne, but points out thalr shortcomings. Cmieer of the urinary tract due to eoal-tar is the noat reeent addition to . the list of occupational centers. It ie moot frequent in the aniline dyo amd related induetrios, 41. Heme Offlea. Kept, of Departmental Coma. to. Consider Xvidenoe as to Oeerurrenee of ^pifKLiamatoue Uleeratlem Among ltule-Bpinaere. (London, 19td) Contains a bibliography on caneer |Mag petroleum refinere. * M. Hunt, X. 8. An Investigation into the Znoidanea of Caaearone or Praaanoerons Ban Lesions Among Tar Yorkera lm. Haw South Wales. Med, f Australia, 8.59.53, ML-S The general mmMhIm la that tar used in How South Wales for local road-eork is not a serious danger. -St* a. z. P. T. Career Beseareh Coaaittee. Carcinogenicity of Spindle Oil*. J. Inst. Pet. Tech., 13 , 805 11957) The I.P.T. Cemrittee h*s not teen eonvinced that the so-called inoidenoc of cancer is In any chape or fora ccnreetec. with the use of apindie oils. at* International Lebc'-r Office. Carclnoganielty of 011a. 9 * Ind. and Labour Information, 3, 273 (1930) Tare at varying temperatures hare been prepared to determine at what temperature oarolnoganio compounda are formed, from which experiments It would appear that suoh compounds begin to be foamed between 500* and 600*, the maximum yield lying between 900* and 900*C. Attempt la now being made to determine the conetltution of a faw apparently pure or almost pure oompounda isolated from such tars. Applying their standard test for determination of oarelnogenlelty, the staff fount that olive oil, neatsfoot oil, sperm oil were non-oeaoer producing and they hare reason to suppose that natural shin fat ia an important factor in the prevention of -eanoer. 59* International Labour Offlat. "Occupation and Health", I, 547 (1*34!; II, 837, 1154 (1934) Before mineral oils came into vogue the practice ia textile mills was to use sperm, lard and neat'e-foot oils and to some extent oaetor oil and eolsa oil. Henry states that ahala oil was introduced about 1930 and Jmarloan petroleum oil about 1344, end that, towards 1372, these oils were being used as components of spindle oil; also that Suaelan oil was first imported about 1330, Htaanlan oil about 1900 and feralan oil about 1909, and all these were used for this slats of lubricating oil before the war. Curing the war Scottish shala alls naturally earns more into use for lubrisating purposes. Oil refiners hare their own private formulae for mixings, but there it no doubt that the balk of the oil sold for lubricating spindles during the past forty yesrs has btsm principally made up of natural mlnaral oil. According to the 1929 report of the Manchester Comer Carnalttea, In the distillation of tars, the earelnogonle products begin to form ate temperature ranging from 300 to 400 C. and reaeh a at between 800 end 900 0, The addition of sulfurie eeld at the time of uae suffices to moke the oil* harmless without Injuring or modifying their luhrieating power. *4. International Labour Offloo. Occupational Tomera. 9uppl. to Oeeupatlon and Haalth, I.L.O., Qeacva (Oct. 1939) Carcinogenic substances are dlseunoed under the headings of hydrocarbon*, aon-radloaotlvc inorganic earnpounds, radioactive subatanses and radiation, and parenttea -30- and microbes. Attention is called to the absence of any ecmon physical or ohonloal characteristics chared by there vriouc oanoar-produeirg agents. It is suggest! that th canoer problem is essentially biochemical end that its solution will ooao vd th tho dlseoTery of the netur* ?nd oeus* of the intrt-eellular chemical change which follow the application of a oireinogenlc agent. . h8 Jordan, E. Experimental studios on tho Production of Cancer 9 * by Gee-works Tar. Z. Xrebcforcthung, ^9, 39-55 (1932) Author has corroborated tho work of others) in whlto aloe treeted with tar for four months or loss, 1004 showed either cancerpreoaneerous ohangea. When tho tar was dietd. at 400* tho rolctllo fraction did not produce thee changes but tho residue produced the typical proliferative ehenges in about 1/1 the tine re quired with the whole tar. lo proliferation could bo produced with anthracene oil. Different alee shewed a narked difference In the rapidity with which they developed prollferetlon with the came ant. of injury by the tar. Apparently the work was not followed to a point dip dot. just how many of tho mite with preeemcerous change a would hove developed actual eartinema* Id, Xmnewey, Z. L. Tha formation of a 0antr-prodelng Substance from Xsoprent. J. Path* last. , 235-6 (1924) *. Xawahata, X. Lung Cancer Among Generator-das lorkaro in the Steel Mills. Gann. St, 54T-68 (1936) ^ During tha past 6 years, 31 ease* ef primary log cartlaoha were observed eaeag the gensrstor-gst worker* at the Teweta Iron-Steel Mills. Thee# worker* have or. aerriee periods of 13 years. In no ethsr seetiams of the mills has sueh frequent appearenee of long eemoor been motised. The workara are ezpoeed to tho spraying of gas aontg. heavy test* The Inhaled go* eemtmlned about 0.74 of gaseous or test-like tar. Analyses showed creosote oil 34.Mll, phenols 0.314, oresols 6.074. maphthol 4.304. anthroseoo 3.604, pitah oil 68.373 sad water 9.740. The metastoses may appear v3ry early in the teals, spinal sort and lymph nodes. Tha duration of lung sender is very short, about 7 months. 17. Ksomeway, S. 1. Canaer-Preduoimg Constituents of Cool Tor* Brit. Med. 534-7 (1934) Cancer formation by tar products waa investigated by author. Only higher fraction* boiling at 890-500*6* war* found active in inducing cancer (creosote, from oil, orude entreeerne and pitch). -51- Xennaway, X. L. Cancer-Producing Tare and Tar fractions. J. Ini. Hygiana 5,, 468--J3 (1024) Sxjeriicants on aararal thousand mlee and analysis of a great mass of ollnloel records indioate that tar oancar is cnuped by a very nail quantity of an unstable compound that exists in the high-boiling fraction (880* to 500*) of a high-tanp. coal tar, i.e., creosote oil and anthreoene oil. Purified anthracene, like all other pure com pounds tried, did not produce eanoer. Splashing vith hot, crude anthracene or creosote oils seams to be the usual method of contact. 8hale oil produces cancer but is less active than gas works tar; crude petroleum is much less active; and blast-furnace tar (a low-temp, tar) does not produce oanoer. The briquetting Industry has reported more than half of the known oases of tar eanoer. Tar made by distilling ooal at a low temperature (below 550*) produces cancer very slowly or not at all. 59, Kannaway, Z. L. Zxperlments on Cancer-Producing Substances. Brit. Med. J., II, 1-4 (1985) Cancer has been produced in alee by substances obtained by heating CSB, ieoprene, yeast, human skin to temps, ranging from 700* to 980*. A petroleum which produced no tumors of any kind in mice in a prolonged experiment showed very active cancer-producing properties after exposure to 880*. 10. Xcsmaway, I. L. end Lelteh, A. The Anatcmioal Distribution of the Occupational eancer. J. Ind. Hygiene, , 69 (1985) 61. Kennaway, Z. J* further Zxperlments on Cancer-Producing Substanoes. Biochan. 1., 84, 497-504 (1950) Carelnogenie substances were obtained by the action at roam temperature of A1C1 on aoctylene, xylene, naphthalmae, naphthalene and bromobcnxane end tetrahydronaphthalcne, the last two being the most active. Two canoers were also obtained lm a series of 10 mioe painted with a sola, of l,,7,S*dibxsnthraocne. a-Phcnylnaphthalsne was prepared by action of AlCla on CaHaBr and Ct#la. The distillates up-to 548*C. eontaiming the hydrocarbon were inactive but the residue in the flask was highly earelnogsnle. Cyclohexane, cyclohexane, styrene, hydrophemanthrone, hydroehryscae, hydroretene, perylcae, naphthalene end various naphthalene derivatives all gave negative results. t. Xeaneway, X. 1. and Sieger, I. Carelnogenie Substance# end Their fluorescence Spectre. Brit. Med. I., lo. 8688, 1044-6 (1990) Thlf paper la e review of e large amount of west by the authors in am attempt to aorralata flueraeoanaa with oaralnogenaals. Tar olla, apindie and ahale oils, which ehow eareinogenie properties arc also strongly fluorescent. i i Aewley, J. Cooperation. J. Inst. Pet. Tech., IS, 242 (1332) Mention of the fozmation of a committee by the Institute of Petroleum Technologists to follow the wont of the Manchester Cancer Committee. Cling, A., Semssonow, H. and Haros, M. The Tarring of Highways aa a Possible Agent in the Causation of Pulmonary Cancer. Bull. Acad. Med. 120, 130-43 (1938) Expts. in mice showed that the tar, as used on roads, produces cutaneous tumors and malignancy in the lungs. A substance oontg. the benzo (a) pyrene nucleus of deeldedly canoerogenic properties has been eepd. from the tar. 65. Cling, A,, Samasonov, I. and Heroa, M. Possible fieletlonship between Tarring of Highways and the Znereeee of Inoldenoe of Pulmonsry Primary Cancer. Bull. Aeed. Med., 121. 784-91 (1939) Since tar eontalne benzopyrene, a recognized oanoerlgenic agent, it cannot be coneldered ae inoffensive. Ixperimente on mice definitely eonfiza this aesvmption. 66. Coalsoh, 7. Cancer end Occupation. Monataohr. Irebsbekampf. 5, 7 (1937) " The author, in the form of an abstract, presents e surrey of the relation between oenoer and occupation. Ha inoludea bone cancer eauaed by radioactive substances, kin cancer from eoot, tar, paraffin and lubrioating oil* (of which those boiling between 250-500* are of eepeeliLl importance), akin cancer from arsenie aa well as cancer and sarooma from ultraviolet end sunlight. 67. Cunze, 0. Mineral Oil and Canoer. Cha. Ztg., 59 . 407-8 (1935) A study of the map of Oexmany Indiested iEat the number of deaths from eanocr was always greatest lm regions where mineral oil wee found, refined or used. While ne definite relation is established, the author suggests the possibility of the existence of such a relationship. furthar research on this problem is indicated. It is pointed out that mineral oil by it self does not eewee canoer. It may, however, beoame one of the oontrlbutlng feotore, together with others. 98. Lane, C. 0. Occupational Dermatitis. Arch. Demutol. and Syphll. 43, 184 (1941) Describee the ease of e 48 yr. old machinist who for i 3 yre. had a dcxsatltis of the fees, ante, axillae and lower abdomen. There were soattered areas of tan-brown hyperkeratotlc folllolas and follicular plugs. Keratoses were present on the serotwn and there were keratosis areas on the mxms. Autopsy revealed carcinoma of the esophagus. Dr. Lame believaa tha akin changes to ba due i M \ i i -33to oil to which the man wma exposed in hit 40 yr. at a machinist, and that tha condition it that described by Whitt emong machinists, oil workers end mule aplnnars in Jfcxgland. It apparently la g"*mly seen in thla country, possibly becauae oils employed here are leea carcinogenic. <9, tauter, H.J., Hildebrand, X. and Behocke, H. Poaalble 6 * Therapeutlo Action of Carcinogenic Hydrocarbon! in Treatment of Cancer. Z. Gea. Xzptl. Med., IPS. 370-94 119 39) Xaaentlally leea harmful therapeutic meaaurea are available. The dangera are demonstrated on miee treated with methyloholanthrene. 0, Leitoh, A. Mule Spinners' Cancer and Mineral 011a. Brit. Med. J., X, 941-3 (19S4) Rendered an inert California oil very actire by heating it. (lo detaile aa to temperature, ate.). Crude olla from Assam, Borneo, Igypt, Burma and Badarpur produca malignant growth!. Galician, Russian, Californian and Persian samplea were negative. 71. Lyth, R. The Relation of Carcinogenicity of Mineral Olla to Certain Physical and Chemical Charaetarletloa of Theea Olla. J. of Ind. Hyg. 13, ttd-37 (1933) 7t. Lyth, R. Molecular Distillation of Lubrleatlng Oil. Batura, 139, 374 (1937) A brief report is given of the diatillatlon of e Scottleh shale oil, using e specially designed molecular atill. The moat striking result is the inversion in the change in the physical properties going up the tempera ture scale, i.e., the first fractions show higher re fractive indices and densities than the original oil, with gradually descending Taluse from fraction four as the temperature is raised. Date on the properties of the shale oil distillates are tabulated. These experiment* ere part of an lnTeetlgatlon of the in terrelation of refraotlT* index and Tlaeoalty to aotlwlty on injection, end thereby oarolnoganlolty when applied to tha skin. 73. Mi eschar, 0., Almasy, V. and Zehcnder, Z. Is There * Connection Between the Benzpyrene Content end tha Carcinogenic Iffact of Text Behwels. Med. Wehnsehr. 71, 100*-7 (1941) The authors haw* tzmlned tha benspyrena content of gae tar in various towns in Bwltsarland, using e method deriaed by Almasy. Then tha tare were purified and their oarelnogenie effect determined by painting on alee. The investigators triad to evaluate tha rasulta by acans of a atatletleal method in order to overcome the difficulty offered by the fact thet many mice die in the long period needed for the experiments. They find a staple, regular relationship between the benzpyrene content and the carcinogenicity Of the tar. Murray, J. a., et al. Discussion on Aroerlmentel Production of Malignant Tumors. Proc. Boy. Soc. (London) BUS . 268-92 (1933) A symposium in which some attention is paid to oarcinogenlc ehsm. compounds, and to the innunochemistry of cancer. O'Brien, H. I. The Problem of Caneer and Oil. Petroleum Time*, 27, 462 (1932) An open letter to the editor of the Petroleum Times (London) in answer to an editorial in the issue of March 19th. The writer points out the humanitarian and scientific values derived from the cancer research of the Manchester Committee end orlticiseA the teohnologloel viewpoint of the editorial. O'Donovan, V. /. Cancer from Handling Anthnoene Coke in the Dye Industry. Br. J. Dezmat. and Syph., Three oases of cancer in a factory employing only 25 man. Phillips, C. Relationship between Skin Cancer and Occupation in Texas: Review of 1569 Yerifled Lesions Occurring in 1190 Patients. Texas Stats J. Med., 36, 613-16 (1941) Prosser-Vhite, R. "The Dezmatergosee" 195-236 (1934) . Dermatitis and canosr from patrolcus produota, shale end tars. Ixeellent rsvisw. Roffo, h. Ixperimsntsl Research on the Production of Pulmonary Tvaors by the Distillates of Pusl Oil. Press# Mad., 538 (1940) The author demonatratad an oil, taken from the stz'eets of Buenos Airee, identical to that from motor car exhaust, which sontains carolnog enic substanoes. Roffo had nifK inhalo the combmation gases of fusl oil and lstsr found s mmsber of pulmonary sanssra among ths animals. By instating a distillate of the fuel oil into the auricle of rabbits, he produced tumors in 80Jf. Roussy, 6. and Oberling, C. Can Tarring of Roads be Con sidered as a Cause of Pulmonary Cancer? Bull. Acad. Med. 120, 161-90 (1936) The danger is not considered to be of significance although ths possibility is admitted. 2ehrsus, H. T. end Zurhelle, X. Xxperimsntal Production of Tutors with Tars from Various Soureas and with Paraffin. Dout. Med. Tochaehr. 49, 633-4 (1923) Author imvestigeted the poisonous action of paraffin -5S- oil and tar constituents by painting mio* twice a week. Aft r six months a atata of malignancy aa obtained with pereffin oil. Coal tar readily develops melignant tumors. Various purified acid and baslo fractions from ooal tar give negative results. The neutral tir oil is moat effective ns a tumor inducer. Schwarts, L. Siin Diseases in Oil kaflneries. safety log., 210 {*ov. 1924) It has been found that workers in oil refineries have a percentage above the averege for oarclaame of the cheek and of the lip. An unusual prevalence of pigmented papil loma t* on the hands, forearms and legs of workers in oil refineries and among machinists in oontaot with oil and grease was also noted. About 10.< of such workers were found to have these growths. The use of totally enelosed manufacturing syatems end of protective ointments is suggested. 94, Sohwarts, L. end Tulipan, L. "Occupational Diseases of the * Skin", 1939, 514 05, Scott, A. Occupational Dome to*** of the Paraffin Workers in Scottish Shale Oils. Brit. Med. J., 3.28.21, SOl-5 86. Sequeira. J. H. Cancer end other Diseases of the Skin Caused by Mineral Oils. Kenya end 1. African Med. J., 6, 13-2 (1929) " 87. Smyth, H. P. Review of Literature for 1926-1934, ine. Report of Committee on Industrial Skin Irritants to Am. Public Realth Aten. 88. Southern and Wilson. Cancer of the Serotum. Brit. Med. J.,, 2, 971-2 (1922) 89. Spademan, J. B. and Chamberlain, I. S. Trans, fareday So*,,, 29. 387-8 (1922) In a study of the eeroinogenic potency of mineral oils, Twart has shown that the addition of glyeerldes reduoes their potency, although no oil surpeseee lanolin in thle respeot. 90* Teleky, L. Ooeupational Caneer. Aeta d. Internat. Ter. f. Krebabekampfuag, 2^ 253-75 (1928) Several isolated see as of lung eeneer ttffimg generator workers have been reported end among works exposed to ' coal dust, ter end ter distillates, but the number la small. 91. Teuteohlaender, 0. Industrial Caneer, espeelally the Types Occurring In Qermany. Z. fuer Krebsforsch. 32. 814-27 (1920) Dleousaes x-ray eanoer, oaceer of briquette worker*. 1 i -38- mule spinner*' cancer, which has not appeared ir. Germany, 2nd paraffin cenoer among thoee who work in tha petroleum industry. Tautsehlaandar, 0. Occupational Cancer, with Special Con sideration of ita Prevention and Legislation on the Subject, *ed. belt, 11, 1867-78, 1341-6 (1937) Occupations In which there is danger of development of cancer are reviewed; many data are given regarding aubatanc considered csrelnogenle, the looatlor of malignant tumors, their latent period, protective measure of an industrial-hygienic type, nueetion* of insurance, eto. There is no so. agent common to ell cerelnoger.lo substances as a promoter of oanoer growth. Teusehlaendcr, 0. Does Tar Bequlre Ultra Violet Light to Produce Skin Canoeri Klim, lohnschr., 16, 1884-5 (1937) White mice were painted with tar. Ceneers developed not only in the irradiated animals but also in those kept in a dark chamber so that not only a preparatory but also an independent caneerogenic effect must be ascribed to tar. Teuteehlaander, 0. Light and Skin Cancer. Ztsehr. f. Krebeforech, 60, 81-98 (1940) The author investigates the problaai of whether or not a photodynamic influence lcMvcssary in the genesis of tar cancer, fie eondusted experiments on tarred miee kept in a darkroom. Line* skin oaneer developed on tha painted skin, it is evident that ultra-violet light la not a requisite in tar eaneer genesis. Tha same is shown by tha development of spontaneous skin aaneers in two wild grey house miee that lived in a briquet factory. Icverthelees there is a widespread belief that both oanoer of radiant source and tar oaneer of the skin are caused by ayelle hydrocarbons. According to Boffo, both types are originated by oxidation and decomposition of cholesterol in the tissues which nay bo caused by radiation as well as by ehamleal influence-- eanoerprovoking cyclic hydrocarbons are finally generated. Prophylaxis must, therefore, guard agalnat the influence of one or both factors. Touraino, A. and Bour, H. Cancer from Lubricating Oils. Rev. Med. yranc. 80, 886-98 (1989) A very complete review of oanoor from lubricating oil*, its oeourrenoe, clinical cymptoma end the medico-legal aepeote of ouoh eecee. Twort, C.C. end lag, H.B. Mule Spinners' Cancer and Mineral Oils. Lancet 1, 758 (1988) -37 m Twort, C.C. end Pulton, J. D. Experiments on the Mature of 9 * the Carcinogenic Agents in **inerel Oils. J. Prth. end Bscteriol., 32, 149-161 (1929) From a consideration of the chemical reactions involved, the authors are of the opinion that it is to benezenoid hydrocarbons that certain mineral oils owe their cerelnogenio properties. Treatment of the oils with sulphuric sold led to almost total abolition of their oeroinogeolo properties, and similar results were obtained by the adoption of methods of oxidation and reduction. as Twort, C.C. and Twort, J. K. Studies or. the Origin oh Career. Ztschr. f. Krebsforsoh., 32, 491 (1930) This is'a general surrey of the work of the Tworts, *nd is based on experiments on 43,000 aloe, a awe Her number of rate, guinea-pigs, and rsbbits, end on the use of some hundreds of varieties of tar? end oils of various capacities to cause oaneer. There is but little pro bability that an acquired physiologioal immunity against oaneer-producing substances exists. The authors' various substances are divided according to their onnosr-fonaing capaeity in mice, to that every group has ebout ten times the power of the preceding one. 99. Twort, C. C. and Twort, J. M. flMsifioation of four Thousand Sxperlmental Oil and Tar Skin Tumours of Mice. The study from which this classification was made was based upon 9,100 animals. 100. Twort, C. C. and lulton, J. D. further Experiments on the Carcinogenicity of Synthetic Tara and Their frcotlons. J. Path. Beet. 33, 119-43 (1930) 101. ' Twort, C. C. and Twort, J M. The Cerelnogenio Potency of Mineral Oils. J. Ind. Eyg. 13. 04-Ef (1931) Pointing mice with refined sEsle oil indueee cancer more readily than painting with raflntd petrolsum well oil. The most potent frsotlon from shale oil is un finished lubricating oil from which most of thw paraffin wax has bsan removed but which had not been treated with Ha80 end filtered. The heavier grade oils are less potent than spindle oils. The oimoerpreducing property of oils appears to be related to fluoresocnoe. Oils having a blue fluoroseenee seen more active than those having s green fluoresoenoe. Chrysene dissolved In oleic sold possesses oarelnogenlo properties. 2 10S. Twort, C. C. end Twort, J. X. The Beletlve Potency, of Cerelnogenio Tara and Oils. J. Hyg., 9. 873-9 (1931) A method has been devised ediereby tKe potency of any given oerolnogenle agent can be compared with that of e standard agent. A unit of earelnogenloity- U.C.- -3H- has been established, and a concentration of 500 carcinogenic unit3 par cubic centimeter la considered to induce the maximum rale tire response in anineLs when the agent ia applied twice a waex. The c rcinogenlc oowers of oils rate as follows, in descending order: Shale, Venezuelan, Borneo, Rumanian, Persian, Californian, Mexioan, Mid-oon- tlnental, Texan, Pennsylvanian, and Russian. Hypothetical standard agent 100.0 Penn, oil 0.1 Cal. pet. oil 3.0 Oil Ho. 3 0.6 Shale Oil 48.0 Pitch 25.0 Gas tar 94.0 Plnene synthetic tar 706.0 Effect of refining Penn, oil 0.1 Methyl sulfite extreat 22.0 Oil Ho. 3 0.6 Distillate 300-380*C./lmm 12.0 Methyl sulfite extract 53.0 Shale oil 46.0 Oxidized at 150-160*C. 0.3 Plnene synthetic tar concentrate 3745.0 Oxidized at 100*C. 2369.0 Oxidized at 150-160*C. 68.0 105. : Twort, C.C. and Fulton, J. D. Concentration of the Carcinogenic Principle in Oils and Tars. J. fuer Xrebaforaeh. 35, 543-73 11932) In the attanpt to assess U.C. by physleal and chssilcal characteristics, the specific gravity, re fractive index and iodine number appeared most pro mi sing, though other features may dao ultimately prove to^f value. 'l04. 1 'I Twort, C. C. and Lyth, M. The Selection of Kon-oareino- genic from Carcinogenic Oils. ? Hyg., 33, 464-73 1192(3) All the animal end vegetable oils teated by the euthors on animals have proved to he incapable of in ducing tusu>r formation during the life of their animals. On ths other hand, oleic add and linoleie acid, unsaturated fatty adds which may ba praeamt in ocomardal eaponiflabia oils, hava frequently Induced txraor foxsetloni observations which in thdr opinion ars of the highest importance in relation to many oanoara other than those of the shin, and possibly even of those of the shin itself. It has been found that the carcinogenic constituents of a given crude are not equally distributed in the various products of distillation obtdned from this crude, ?he activity of the first product# to come over -39 in ths till, th motor spirits, to., is negligible, end that or ths lamp oils, burning oils, light fusl, etc., is also of llttls accountj but when we roach ths boiling range of ths lubricating oils a definite o?roinog9ni3 -.ictivity royr become manifest. Among ths latt-sr t.ia moat active grades era, on the whole, the swindle ,'ral's, closely followed by oils of a Redwood viscosity of 500 to 1500 at 70*F., with e gradual decreae* in activity as one approechee tha internal combustion angina (motor oer) gredee. The crudo oils thamselvas, as a rule, are somewhat last ootont than the motor oer oils, but of oourec. It will necessarily depend upon the amount of refining to whioh ths latter have been subjected before being marketed. tOS. Twort, C.C. end Twort, J. II. Carolnogenlelty of Spindle Oils. * Oil end Colour Trades J., 91, 1193-4 (1937) A physical and an anlmal~test for carcinogenicity and e physical end an animal teat for dermatlelty of mineral textile oils.are described. The overage results of these testa on 64 oils (including shale oils) colleotsd 3-10 yr.ago and on 66 oils oolleoted recently are tabulated. (The animal test for oarolnogenleity is not yet completed for the reoent oils.) These results indieata thao tne original oils are definitely woree them the recent oila In both the dermatitis tests, while in the eanoer physical test there is no signifi cant difference. It is exptoted that the figures for the reoent oils in the animal teat of earolnogenlolty will, be lover than those of the original oils. It is concluded, however, that little is being done to improve mule aplndle oils from the biological stand point. There are aleo Indiaations that the average oil used in some of the codton-epinning towns is more dangerous than that used in others. Twort, C. C. and Twort, I, M. Iotas on tome of the Procedures Adopted for Assessing the Biological Activity of Mineral Oils. Oil Colour Trades J., 94, 8S1-6 (1936) Mineral oils may induce fleamtitle or eanoer ef the elcin. In detg. the carolnogenle esneet 3 essential detas. are made: .d., n and Iclnetlo viscosity (AT). The date oolleeted are based on the utilisation of formulas for assessing the Mol. activity, especially from its oaroinoganis aspect. In formula A, 1* (n-l)/d where la sp. refrectivity, xw refreotlvs Index end da density. In formula B, la n-(d/t). formula A la-used in obtaining tha eanoer refraotivity Cl from formula C which la C! BeS(d-0.900}/aD. In formula 9 tha refined eanoer re fraotivity BHUC3- (ST/SO). lesults, where these mineral oils have been employed, ere shown in tables in which mineral oils are grouped aooordlng te toxiolty and -40- aeoordlng to the n drop. The significance of d. 1b relation to the n drop among oils of similar toxioity and tha significance of viaooaity in ralatlon to tha n drop artom; oils of apparently similar toxicity are shown. Ihe real difficulty in arriving at the true biol. activity with greater accuracy la the lac*; of uniformity of the im>rt fully hydrogenated constitu ent*. niero is quite good correlation between car cinogenicity, refraetirity, n drop and toxicity. 10?. Twort, J, M. and Lyth, R. The Concentration of C*roinogenio 1 Materials in Mineral Oils by Distillation Processes, J. Hyg. SP, 161-9 (1989) Twelve acid-treated lubricating cuts of a crude, Borneo pineral oil, were tested for oercir.ogenic tirity. The whole range was biologically active, which activity had bean foreseen from nr examination of tha physical characteristic!:. The peak activity wee around a vis cosity of 800-250 Centlpolaes at 88*C. Molecular dis tillation gave a greater concentration of the carcino genic materiel than ordinary distillation, st from 5-10 am. In confirmation of previous findings, the middle fractions of a Borneo crude oil ware mostly responsible for pathological changes in the organa--fatty infiltra tion of tha liver and hyaline degeneration of tha aplsen. Lung tumors were more prevalent than is usual when this type of agent la used for testing earelnogenlty for the akin. Their incidence eaa rather higher in tha mors viscous fractions} this incidence was apparently not correlated with eareinogenlty for the skin* 106. Tmort, J. M. end Lyth, 1. Skin Cancer due to Handling Coal Tare Used for Preservation of fishing Seta. Mature, 144. 446 (1989) Several fisherman contracted oeneer of the skin after handling the tare. Mouse expte. showed that different ooel tare differed In their oaroizxogenie activity, although all produeed sane cancers. Creosote oil and anthracene oil were also oareinogenle. Only ooal tar made in vsrtleal low-tamp, retorts should be used an nets. 109. Twort, C. C. Mule-Spinners' Cenoer: The food for Using the Correct Oils. Oil-Colour Trades ?., 8.29.41, 386 The oanear-proftuoing powers of mineral olio used in the cotton industry from different fields of origin, in tha erude sad refined states, were thoroughly exmined and the results showed that there is a danger of any one producing oanoer of the skin if applied long enough but the oils from certain fields are the more likely to do so. Special attention was paid to the examination of tha physloal eharaeteristics of various mineral oils, and it was proved that e knowl edge of their refrnotive index and viscosity provides \TS* -41- a more reliable estlaete of their canoer-produoing powers than the application of the aaaple to the akin. Thit test is accurate, rapid and inexpensive, while that vith the eicir. la variable, lengthy and costly. The chief lins of inr-litigation hs been a continua tion of tuft Aori: or the molecular distillation of mineral oils *lth the object of isoletlcg the eubstenc&a respon sible for their carcinogenic activities. Animal experi ments v.itn fractional distillates fro* e Venezuelan oil are in progress, fractions obtained by moleculer dis tillation of a carcinogen! shale oil hr:ve been subjected to chromatographic absorption and two apparently pure hydrocarbons have teen isolated in small quantity} these are being Investigated chemically. Painting experiments with fractions obtained by this method have shown that many of the* are highly toxic for mice. lone of the subrtanoaa so fer tested has been shown to possess s high cercinogenlo activity. A few spindle grade oils and three oils Intended ee vehicles for inseotlcldes have teen tested for orreino- geniclty. ' A colloidal material intended ns a protective against onreinogenio oils has teen tested. There are indications that it has some protective action. The ocrcinogunlc activity of two products formed during the purification of carbonisation gas bean tested, and found to be less than that of the averege gas tar. Ullaann, K., Qppenhei*. M. and Kills, J. fi. J, Ind. Bygians, 8, 286, 364 (1926) -- The lesions caused by crude potroleu* ere the sane aa thoae caused by crude coel tar, showing the analogous substances must be present in both. The final products of distillation are tne Boat active, espeolally'paraffin oil. The carcinogenic agent la praseat in fraotiona from 20C*C. to 480*C., but it la cot oartaln that the seme substance oausea both dezsatltla end eplthelloaa. alade, P. Canoer of the Hunan Lung from Dust fro* Tarred Roade. PreeoeUad., 2.1.59, 161 an Thortsoba, 14. H. Chart eal Cnnoor. Ing. Chi*., 20, bO-5 (1936) More than twloe as many cases of oenoer due to soot were found among sweepers then saong any other occupa tion. Personal cleanliness and clothing that fits tightly around the extrart ties and around the neok are tho best prevanb^tlvea. Siailar ears will do *uoh to ward preventing cancer due to exposure to gasoline and its derivatives, paraffins, oils, and greases. Such precautions are even more necessary in cases exposed to tar, pitch, rosin or aniline dyes. Strict aedleal super vision and the use of proeesas whioh avoid ocateot of the workers with the product wttBSL further reduce the danger. -42 Waa3l*r 7. J. Oecupetionel Diseases of the Skin (by ll9, ` L. Schwarz). "Industrial Medicine", 1945, 327-9 Chimney sweep?' oer.Ccr hec been rerorted in Ireland more fr*-.:vcr.My t'r.^n in jn/ otasr country. It ia acid . tbet the incidence jT c-r.air wrong cr.lnr.ef sweepa ia cisnt tires sore common than among the general populu- tlon. Cvicor of the sorot.ia of chiamoy sweeps, however, la- on the decline in Inglend v it ie reported ss being practically non-existent in other countries, except for an Isolated caee or ta in Genany. The local irritation and rubbing in of the soot as the sweep ia oraa-pad in deeoending t.ha chiimay ia said to be tna o*ue. Ter ia used in building roado, in making roofing paper end felt. Pitch is weed for making conduits, lec'juerei insulating material, gretaes, and Minardi cementa, ar.d workers at theee occupations ore affected with camadonac, timiors, warts, keratoses, and epifche- Horn*, sostiy of the scrotum, lip, faoa and .hands. No oeaes of mule spinnero* cenoer hare bean reported from Prance, Germany, Eus'ir, or Poland. Tna author made export, nations of thouamds of mule a pinners eaoloyed in the United States and did not find any eases of sorotal cancer, although there ware many eases of folll- oulltla and ceratoees of the thighs souaad by oil- . soaked trousers. 114. lanlek, R. Melanoderma and Keratoses from the Aotion of Asphalt. Anti. 8*ohverst. Ztg., 66, 49 (1340). In the preparetlon of oork plates (heat-insulation plates of asohelt and cork) much dust devnlops under ary unfsYoreble working oonditiona. Two workers, who had been working for three months, suffered from pigmentation, infl'-uamatory changes and hyperkeratoses of the feoa, forearms and hands. Ths hyperplastis prooeseos vara intensified in the older workers. The sjenntona were aggravated by light. Iha intensive aotion of asphalt dust is considered to be the cause. 115, Vataon, A. 7. Tar Cancer In Mice. III. An Apparatus for the Preparation under Standard Conditions of a Highly Potent Carcinogenic Agent of Low Toxicity. Brit. Jour, dxper. 11, 441-7 (1951) kith an adaptation of the apparatus of H-^ua and Wheeler the author has succeeded in making from purified turpentine, et S50*C., a relatively non-torlo war which all cited tutors after 210 days in 90 of the survivor* from a group of 37 rice; most of these growths ^ara malignant. Ul. Welwnrt. Ceneer frar ?raffin Wax end Mineral Oils. r>eifena. 2tg., 62, ^92-3 (1935) Moat chemists md dermatologists believe that workers in paraffin factor!-*s G"t cenoar fron the paraffin ituelf -43- whlle Baherber and ?eutechieender claln that eancer doe# net cone fro* paraffin but fror lalnaral oil*. fljtdaue, A. eitd Kennhak, E. fsao Di*J v^tivsr of 3,4-Ben>l*f* pyrene. Z. Phyuiol. Chaa. 849. 2Se-*fi (1937) By onaioy tc x-rayo ("x-rv produce and x-r*ys cure Of-ncer* # carcinogenic hydxocarb .** should be tested for possible therapeutic T&luaa. Sug^eatiTS results hers bean obtained with 3,4-bentopyrene (IK food, ?r C, The Ion-Carcinogenic lature of Pubiflad Mineral Oils. J. Jka. Mad. Aseu., 94, 1341 (1930) The general oiinio&l erldanca that there exlata no relation between the therapeutic use of refined petroleun products and the occurrence of eanoer is eosflmaad by expsrinantal atudiss. ns. Vast, I. B. Paraffin lot Productire bf-Censer, X. Ctnser ... Bes., S, 97-108 (1929) tea, Vood, E. B. Shin lesions Among Tar Voxfesre. X. Censer Bos;. iS* **-* U989) Different types and composition of tart art 41a- eeseed. Only tar obtained free the dlstn. ef seel at fclgi tsnps. contains a substano# oarslnecsnl* to ssrtslm ' 1st. wiaais. Vorknan handling seal tar shooed tar sorts as a result, tat no other offset, VO irritant aotieo on the human shin ms found Mh low temp. ; ilstillsts ter or free petroleun ta'r. * 1U , B. 1. Cerelaagenlolty of Synthotid Imbricating Oils. X. Inst. Pet. Teeh., , 1007-43 (1434) 1SU m end lehil _ Study of ... of Carelnsna. X. Comer lea., IH,1-X1 fltlS)- In 1919 produced sen ear by the cxpcrlmnftal gjlfwllla ef ter te the mat of i laboratory animal. * v . .'i t \ i