Document J3JZq0Y83nr6EKvzno8kDayEe

FILE NAME: Shell (SHEL) DATE: 1950 DOC#: SHEL024 DOCUMENT DESCRIPTION: Book Excerpt - Environmental Cancer and Petroleum ARTICLE 3 Environmental Caner and Petroleum iUllKUD.jDlL*!< I'HOPhH'rn BTC. .J.IilXlMnNTS van Vk-iningon lor saleable discussions ildijke,.'Shell kahoraloimim-Amsitordiim (`i cnees. k, K. VV. ' A.1M ilnlhnR and (.rouu<;l ion 8, H5 U)4H, 44, 531 'Dili lk4{i, 13, A 101. (n'oL 01, (52. liolio. Oc<.. 1030, OS, 1. 1 ENVIRONMENTAL CANCER AND PETROLEUM.1' i By kr.-Cor,. S. J, , Acus, O J K., M 0 . ( i'ad~ri`esidt,nC., Mobkrm industrial <bs ilim tbn hits brought in its train many added dangers to mankind. Not the least of them* are tho occupational diseases resulting from exposure to conditions arising in the course of rnamdaeMmiig operations. Sometimes such iwlvmw effects come from tlio absorption of defimfco poisons. In that case steps win In; taken for the purpose of nmeliorating Uto environmental conditions. in any event Uto course oi the specific poisoning can often lie followed ami knowledge built up for the prevention and treatment of the ailment concerned. That is par ticularly the ease where the poison is recognizable and is yiiiolc in action. Where the effect is slow or a lengthy latent, period exists, culminating I in sudden and often apparently unrelated illness, recognition and control 4 oenf vtihreondmiseenatsael icanmceorre -dwifitfhicuclat.nceTrhiantdeisedgoansuma lwiyhohloew, wifhehraeptpheensinwitiitahl 4 impetus given to the uncontrolled coll growth which constitutes the disease is often unknown because of the long latent period which follows. That is regrettable, for, with few except ions, the causes of cancer so far discovered aro o f external origin. If is, unfortunately, also true that at tin* present lime only a fraction oi I per cent of all enucors can he Iraced to known causes. To be able Ln trace Uto origin of tiny cancer w, con- sci|ucully, of the greatest possible value in the building up of our defences I in what the whole world is realizing in the gran lest ImUie of all time which 'I malnl liisasfolritrfei!ntcoh wraaigseo.ns Mint the appearance in ihis field of the petroleum industry is to be whole-heartedly welcomed. The oil industry is the most higidy organized and most scientifically controlled of all the world's great f industries. The fact that its direct participation in the causation ot cancer appears to he Htimll is of little account compared with its resources for the 1 collection and recording of data; and in particular its ability to tram effects to identifiable materials, to renditions of production and in 1 mclhods of handling or application, 4 Ju order to show how the oil world is helping to-day, and largely i:i Great Britain, in establishing a link between wui.se and effect at least in f ucenpational or environmental cancer, it is necessary first to sketch in the background of proved or suspected causes of environmental cancer, i and to proceed r-heref'mrn to the particular case of the hydrocarbons and then* association with petroleum and its application. 1j sta'Tnhdeinagu. thloire'sisponsoittioan mmeudsictalliemnamn tloor caleabriotloogipstr,evaenndt ahnisy amssoiscuiantdioern i with this subject is that of an oil technologist. However, for many years ho 1ms helped to represent the petroleum industry, through the instil nit: ( of Petroleum, flu* Petroleum Board, and the Ministry of Hnel and Power, ISlflO.i An R(kli':; to tho Northern Brunch ot tho lnstituto at I'olrnleam, January t7, ft. ->! -i l>l.M . lv.\ill[U.M!l-AI U, CAiNOKH \ NO S' KJUui.M, ,ll. in 1tioi.* various! jo in t diRewseious wif.i\ {Joveriimenf ami oth er boding rou rcn icd w ith th e subject. Hfu can, thorcfoie, discuss th e su b ject with Mime knowledge an d au th o rity , but m u tt em phasize th a t his specialized in terest is th a t of oil. K n o w *! O a i i s k m o n O a s u k i l The recognized ami established carcinogens an; generally either physical or chemical in nature. The physical include a-, T , y-, unci X-rays, and nltm-vidkb light. T he chemical list is a long one, and is continually being extended. lluoper 1 lias classified them approxim ately as in T able 1. TAHU5 T. Inorganic. Arsivme Chromates Niokd (KU'bcnvl Asbestos -Beryllium ',v j Organic, j Avmnatie ammo?. Aniline " Oenzoie. Polycyclic hy<t'oem-bons item.. (kubou black, T'.u- uml pitch "Paraffin oik" Stutio O.l. Militant Oils Anthracene oil, Oieoseto Aco dyes * Oeat rugous " " Conflicting evidence. These are placed in T abic IT in th eir chronology of discovery, with notes added as to the investigator, the organs affected, and the nature of exposure. !Va b l ,e I I (Alter Ifncy/n) Dale. M>fi . iT7." Armenia i K22 Vnimtfu ol1 , 1^7.5 Hliaic rT U>?6' Fi-.cH anil hn 1879 Onulo a}]? (son.n) . 1879 Mm (jilirn violer-) . 1809 At'ornatifi Kinim-h 1895 hUcohiU!`f*t{CoApmmT<y.tahematuhimu m )i urn liontgen ray;-:, radium ion Authrucftiw oil to u Betel uu&t fobi coo h)n Vh'il 101.0 Radium 1920 ImiiruniAIni? oils i 922 Creosote 1924 TtanMo 1928 Uianium 1029 Ktulioaotlve rro 1931 Chromates . 1932 .Nickel carlc;ny] 1002 Asbestos IVtdkmcfcivo Tays Tar fumes 1004 I 1904 1009 T)m'var"r. 0 not s aft'cfftad ; Nuhue oJ Ayi l<m Voilnnau'i M,m (saifMmst) KUm M?m Bed Yn ftouvr':!/ MsirKug and Tftsso Buna. Re m Von Jagicx, o d o n n u , mul Von HieiKiiruck llauhnusek Davis iWmmha:; awl Geuud M;in Skin Slcm Stem Bladder SI: in UlnddiM Bono marrow (N'tiwwm) m m Almith l,iW! b d U ij and ftoquiru HnuMiohi and WUroii Coolcson Ddore and Bergamo I,awry Mart land Alcvcna Stephens Skin skm Hkm : Bone >wmms Ck*uciml;t) ? MU5 ? l:;mu* Bang Ximd sums^, OcrAeliiimi.y sUta-ptf) Oee,, env. tUv. tlignUe and Mt/?D oil IminsDy) On*. Oec. Ore. (faimm. Or<\ five Hulmorv) (Jiv., mod, Knv. net*. (IC&'j <>D uec., sued, Dec, Habit {Imiia. Malay) l)nv. (poverty diets, African^ VliitnaaO Occ,, sued, Ore. (muii* apimter.O Oi'i% 0<v, Oec, Oca, Oft;, Wood and Oloyne Jantp Oee. N<*U/e! 3-uiig Oct;,, me-]. Kalwivate * Occ. * oceuiiaUonalj anv. --environmental; med. ^m edical. Nf'! I! livr'm s .1 Lmi'urtii'it ;uul iuU;n'-hf!m; m, f ( ,, mental (nuiacfirm, `.hnce tiikiil?!,- ) , , 1,,. mu problems ;ivr. !(>ot; pnr.Uhii , ; g , Ucnzolc, .iiithniarne oil, ,vl civocrii ,, A ttention is dimcle.'l to fho f;ici i h.,; . oils." which in ;mj' c;iou i; <i vtiym- cntl , , j tile subject of our special iulere^l, ,.'l ,.i i j chemicals are m*ugiji?nbly hhuimiIh u, ,, coriditiourt of heal which ;ne?ngc then- m j a|>jlie even to the so-eallc/l ' puMtitu . to be the cause of cancer aineiutct, industries. In gt'iu.Tal, it applies ,i|vi. j outskirts of our piovmce, like the ,.'.<>rl % 'ITio oirginal obseiwntirui.s fror -hi. h . em anate are rhoso of Un- celelji in.-d ie Ht. Bartholomew's llnspila,], .uid i m i h- His diagnosis 1ms nlrt*a<ly been quoled bis impoi'tani address to the K u rd I us!, and (ameer. If refers t,. PnU.V, tveogiuf as r. speeiJic disoaso, i-oneeiTiing whu h 'is '' It is it. disease winch ahc,i,\s m iirsf ipipiKirmtee in, the mfci'ier p,,i'i duecs a suptM'firial. p'untul, ragged rising edges, The Irad;? <"dl it so, people seems -singularly hard, m Hi. frorpicutly treateo with grei,!. Innn, cold and hanger, they nre ihrusi ehiinnies, where they are hnnscl and when tliev get t.o pnbeHy l>.?u 1 noidomc., painful and fatal disease "' Of thic last eireamst.-iiieo there i perhaps it may not have bean -mil generally known. ! " The, disease, m those people. - lodgerneui, of soot in the ruga; ot tin T'hin ti'omeudon.s'y iinpnrtant elise-vat one hundred years, RoporN then bega other forms of rnneer in workers eonne Tliose, tegofher with nnpurt.K from the i " mide-spiinners' (?aneor " ot the eottim i of ir.dustnid, or at any rain oeuip'diimah Sineo lfilfl, when Jtvpanoae wo `kei-s first . for the laboratory examination of euis'i'.i been ovor-expa.riding olwervatuai m.d ne-. ti things, frequently themical, 'amount'.-ed olrsnrved lactfleie-e ot cmiet'C. f t e-e m gressivniy shown Unit raw far. and Simi 'I 400" C, fiontainefl the. ca-reinogei t- in.d' 'Tins was (piickh followed by the re? m ! u d 1 ns with Govern moil I. and o'her homes can, therefore, discuss the subject with 1ml must emphasize that his specialized .MMBS Oil' Ca NOOR. carcinogens are generally either pliysieal sieal include fi , y-, and X-rays, and s and is continually being extended, ipioxiinatoly as m Table I, T o m e T. Orgiodo. m.itjG ainmps, Artiimo k zolo. Polycyclic hydrucarboita t Oarlwm black. Tur and pitch iruHiu mi." iShulo Oil. Mmovftl Oils hiMcono oil. (JiGOSOt dyi'f? * trogons * doting ovidoneo. their chronology of discovery, with notes rgans affected, and the nature of exposure, T a iii.b if Alter Hui'iiei) St'OVi'l . \ OriMns \ Xdhnv ol '`Xj.asmvi.* ij Oo:. (flimm VsR(,|V) i Sk-n Oec. eov, | 1 , rtJr n W. .olmlo i Of i'U'i.d 1 W j. 1 SKm Oft1, ;/ j Bkm Oec. 4 ml U .Skin Ope. f f-Udn (>(`C. {friUTfjCK `Rdk>ir; } IHnddei Oec. (dye rtidirnii-y) HJoii Oec. mod. Bladder j'jnv , oec, i Bayvd) 'f l /, rtt ImnJ/, lit! j JkJllC IHMiT-OH Oce iued IiUUT'cL k Oec. | : Mv n ik Habit (irdif . Malay) utd Uemrd i .ive'i Jf!nv (novelf iHots, AiVica t- n .nose) i 1 Kkill Ore. .nod dm! WUv:n l Skin Off. (imiif -a auer?> I Skirt Off. i il Boiemiio 1 Unite iiinw Od. if ; (Ifiwrt-mkis *'rM ! 1.11118 Oft). 1 lkrac Oec M>K < T.mtM, Oec. if Oce. Inn*? l G!<n in* t l.nnR Oec. / ` f.Ullg oec. n:ed. : \ | -twin Oct, ' :i A ii.it : i;n \ r ' i n v i u r . T U n v a d i w o I ' M ' u o u u 'ti TT; Important and interest ing as are many ot.hor of the forms of environnient-n-l causation, those tabulated which have a particular baaing mi (.nr problems are soot; paraffin, and shale oil; pitch, tar, and tar fumes; benzole, anthracene ml, and creosote; and lubricating nils. Attention is directed to the fact that, with the exception of " lubnnitmg oils,'' which in any ease is a. vague term '-homioally spunking and is largely 1he subject of our special interest, all off hose organic materials or individual chemicals are recognizably aromatic in nature or have boon formed under eondit.inns of heat winch presage their content of such substances, This applies even to the so-called paraffin oil," shown by Volkmann in 1875 i,o be the cause of cancer amongst workers m the lignite and shale-oil industries. Tn general, it applies also to the organic chemicals on the outskirts of our province, like the azo dyestuffs and the aromatic animus. The original observations from which our prescut-day lines of enquiry emanate are those of the ce.obratod surgeon 1W iv a lt Pott, P.R.hb, of Hi Bartholomew's Hospital, and recorded by lure as far buck as 1775.2 His diagnosis has already been quoted at length by Prof. <J. W. Cook in his im portant address to the Royal restitute of Chemistry on Chemistry and Cancer 3 It refers to Polt.'s recognition of chimney-sweepers' cancer as a specific disease, concerning which he says -- " It is a disease which always makes its first attack on, ami its first- appearance in. tne inferior pari of the scrotum ; where it pro duces a superficial, painful, rugged, ill-looking sore, with hard and rising edges. The trade call it soot-wart. . . . The, fate of these people see,ms singularly hard; in their early infancy, they are most frequently treated with great brutality, and almost starved with cold and hunger; they are ilm tsl up narrow, and sometimes hot wuninies, whore they are bruised, burned and almost suffocated; ,vid when they get to puberty become peculiarly liable to a most noisome, painful and fatal disease, " Of this last circumstance there is not the least doubt, though perhaps it may not have been sufficiently attended to, to make, it, generally known. " The disease, lit those people, seems to derive its origin from a lodgement of soot in the rngaj of ilu; scrotum ." Tins tremendously im portant observation lay practically dormant- for one hundred yeans. Reports then began to appear regarding skill and other forms of cancer in workers connected with the coal-tar induslrv. These, together with reports from the shale-oil industry, and later the mule-spinners' eu-neet " of the cotton industry, indicated the existence of industrial, m at any rntu occupational, origin of specific- forms of cancer. Sine 1915, when Japanese workers first used modern biological technique for the laboratory exa.mina.Uon of causative agencies of cancer, there has boon over-expanding observation and recording of data connecting actual things, frequently chemical, encountered in the industries concerned with observed incidence of cancer. Tims, in the coal-tar industry it was pro grcbsivuly shown that raw t-a-r, and thou particular fractious boiling above J00 0, contained the carcinogenic materials which wen' lining -sought. 2 i A U M l . B N V IR ilX M R 'J T A L I'U l i'K R A \I > i' KTIOH.K'J.M M i 1 i:V V 1If;'.*, int.rogon and sulphur, th at the most active bodies concerned worn in fact hydrocarbons. P ( J P' > i>i h.x,;< fSf ( t , < f , , , , , B io l o g ic a l TiESTrxo. It is n well a t this stage to explain the tost procedure iw tl by the biologists in determining tim oxtwit and con run of cancerous activity. The tests ro made on living animals- chiclly mico, rats, rabbits, guinea-pigs, dogs, and monkeys. The most extensively employed are mice -partly because of thoir susceptibility, partly because of tho relative rapidity with which results can boobluiuod. The question m ust arise in the minds of oil men, or scientists in other spheres of* training and activity, whether the disease so induced in anim als is the same or similar to human cancer, and whether the effects are or are not generally otherwise comparable. Also, in respect of the repro- ? dueihility of the tests, their quantitative sulTieionoy, and the satisfaction by statistical procedure of elimination of other known or unknown , conditions which might affect tho conclusions to be drawn. All of those matters am of extreme importance in biological tests in a way much ; less known to the chemist and physicist, whoso aims to produce like results from like conditions are comparatively simple in the mutter of choosing tho conditions. In the past these points greatly comiorncd those oil technologists who ' wore drawn into consideration of the problem of carcinogenesis ; they have satisfied themselves th a t the procedure is standard ami fully accepted ; that tho standards are scientifically high--th a t is, they are fully organized in detail and understanding like those, for example, of the methods of the institute of Petroleum. This important m atter might bo summed up to the lay technical man by saying : tfoM SImlt< oil Pitch anti tnr Aiitiirnoono oil bubriculing oils Oreosoto Uonxole Tiir fumes ^NopHtliylamino HUif! \am% *SkiM limig' Skin Skin Skin Skin Bono marrow bung Bladder i: M i'irr M'W, Moir-re, ,<i Motjs-.' Mouse 1)oif * OoTfili.'tlW t y sufficiently the past history of their str.i all the natural ills to which they iiv p: required for tho tests, extrapolate>n of re when tho quantitative factor is mum! ,* os a result of starting out with inxuUiH* sumo oxporiinenfal disaster-. But am <*v for th at matter, can obviously be very do th at biological tests must bo conducted wi care in respect of such com!ilium, as ran () 'The results are generally ropontnblo and reproducible. Even if there wore nothing else to the procedure, this would constitute it n valuable observation and non-committal test. (h) The pathological effect* produced two constant and closely similar to those of spontaneous and human eaueor, ' (} Difference of susceptibility or, as wo might say, tho response, of the various animals is recognized; and in the event of cheektesting being needed animals tip to and including the primates are available (Table III). Tests on mice, as being the first, greatest, and host-organized screen, are therefore very im portant. The great laboratories use mice by tho thousand. '['hey are bred from constant, suitable, strains, and are user!, or should be T hk Cakoisockmc H . The recognition that oxi.rm-tt. from tars wore themselves carcinogenic .stilus single chemicals capable of producing mu the pioneering work of Kir Ernest Kenm produced tars was important by diroeim. aromatic hydrocarbons, and encounuxinr causes of coal-tar cancer, Evcntiuiily. re tracked down in coal-tar pilch a .strong!; benzpyrene (Fig. 1). From 2 tons of pi 7 g of the material. used, at the same approximate ago and condition of health -and, of course, I fed, housed, and generally looker! after identically. In a modern laboratory ` they are, as test materials, approximating the standardization of chemical > test* reagents. Oho aspect of this biological test technique to which, attention newts constantly to be paid is the quantitative or statistical side. Even with tho quick-living mouse, a scries of tests requires about a year for com ;t: t iteiupvivne. ' pletion. This is a big proper! ion of a mouse's life. It is necessary, there- J Tho " tracking down " of this hvdruiau fore, la use enough mine for any test, and at the same timo to know hits more than academic interest, li : A .l. ' A n c k j ;. A N D D K T ilO I.lU 'M . iosi active bodies concerned wore in fact iio.vf. T bstjnt!, explain tho tost procedure used by tlm ; ait and i nurse. of cancerous activity. j! a n im a ls --ohiclly mice, rats, rabbits, . Tho most extensively employed are reptibility, partly because of the relative s obtained. : minds of oil men, or scientists in other vhethe.r the disease s<> induced in animals f . cancer, and whether the effects are or a parable. Also, in respect of the repro- 1 ititative .sufficiency, and the satisfaction 14 ablation of other known or unknown ; : conclusions to bo drawn. All of these icc in biological tests in ft way much physicist, whose aims to produce like comparatively simple in tho m atter of y cosieornod those oil technologists who >f the problem of eamnogonesis : they procedure is .standard and fully accepted ; iy high--that is, they are fully organised those, for example, of tho methods of important m atter might bo Hummed up g: fly repeatable and reproducible Even the procedure, this would constitute it in-roinuiitoU tost. to produced aro constant and elosoly us and human cancer. .lity or, as wo might, say, tho response, w.ogni/.od; and in tho event of cheek-- up to and including the primates are greatest., and. best-organized screen, are rat laboratories uso mice by I he thousand, able, strains, and aro used, or should bo ; and condition of health--and, of course, .fter identically. In a modern laboratory cminting the standardization of chemical est technique, to which attention needs ntitativo or statistical side. Even with of tests requires about a year for eomof a mouse's life. It. is necessary, thereV tost, and a t the same tim e to know U ' l.D TINA IF O N M U N 'M l, f , \ M ; \ m < n tn io L K iA i. `fo il T aw,is 111. Np.pi'odttniioh of Oc.ottpahontd A ',/n v , in A iu-mul^n AgcnL Son1 fthttlo oil Organ, Skin bang Kkm bur.)> specie's* i Rdhbit,^ moiio UiHIAC Mouse Mou.se Pitch and tar Authraconc oil Rubricating oils Creosofco Ben'/olo Tar fumcB j5*Nophthyianiino Skin Skill Skin Skin Bono mfmuw Lung Bladder Mouse, gout, rabbit, do# Mourns Mouyo Monso MoUsHQ * Mouse " Monkey Rabbit, goat, mou<so 14 Conflicting ovidonro. sufficiently the past history of their strain, so as to bo able to allow for fill the natural ills to which they are prone. Because of Urn long time required for the teste, extrapolation of the results must ha very tempting when tho quantitative factor is found mmiflidemt. T h ai might happen as a result of starting mil, with insufficient living subjects or because of some experimental disaster.. B ut any extrapolation, or filling up of gaps for th a t m atter, can obviously be very clangorous. I t is for those masons th at biological tests must- be conducted on u vast scale and with meticulous naro in respect of such conditions as can be controlled. TlIJC (lARCmoftHNK! IlYDKOOAUKOtftj. The recognition th at extracts from soot and from rancer-iinnl-icing tars wore themselves carcinogenic stimulated interest m tho search for single chemicals capable oi producing malignant tumours, In tho scorch the pioneering work of Sir Ernest Konmiwny oil carcinogenic artificially produced tars wa important by dirooting attention towards the complex aroma,tic hydrocarbons, and encouraging the search for the individual causes of coal-tar cancer. Eventually, in 11)112, Cook and his co-workcrs trucked down in coal-tar pitch a strongly uaroinogouie hydrocarbon. .`1 : tbonxpyrone (Pig. 1). Prom 2 tons of pitch they woic able lo separate 7 g of the material. /\ /\ 1 \. V/ ;s : 4-H(inzj)yrnno. tin. \/ 2- (teimuithrucano. The tracking down '' of this hydranarbon was done by a method which has more than academic interest. I t may readily be brought to the T 210 ATM) K.W'lKOA'iii'A.'TU, \ X ' i I' KTRiM .KrM . attention of oil men and questions asked about it. It Ih/w orew ncc. It had been ohseivyd by Mavncord .md Hicger, who collaborated with Cook, th a t the eai emogeuio tars were all strongly fluorescent and possessed fluorescence spectrum bauds of similar position ami distribution. Horn was a possible quick oluo, without having to wait lor the results of biological tests each of which involves trinity months or years to complete. Con. r.entralion of the extracts using this means of control eventually resulted from a variety of methods, including the chromatographic, in the separation of the 3 : 4-benzpyrene described. This has a closely related si mature to 1 : 2-beDZHJdhmeene (Fig, 1) which, though itself inactive, has a similar typo of fluorescence spectrum, partly in the visible. Tins synthetic material is the parent hydrocarbon from which nearly all the highly active carcinogenic compounds of this kind are derived. I t is clear, then, that although fluorescence accompanies the general structure of the hydrocarbons belonging to this important carcinogenic grouping there is no relationship between fluorescence and carcinogenicity. First, there arc m any known caroinogwis which are not fluorescent at all. Secondly, although Iho active hydrocarbons of this kind are largely fluorescent, the reverse is not the case- m is soon from 1 ; 2-bonzanthra.eono itself, Thirdly, it is not fluorescence, in. general which is characteristic, either visible or under ultra-violet light, but the analysis of the spectrum and its classification. These arc points to be borne in mind, since as a result of Ilieger's im portant. work ill-advised generalizations have sometimes been made and suggestions offered, in respect, of oils and other materials, to use fluoresce.)]co as a classification of carcinogenicity and as a guide towards Urn use of particular irm-torials, Of the many hundred derivatives of 1 : ^-benzanthracene which have been prepared, many are inactive, others only slowly active, and others again very powerful. I t depends largely on the position of substitution and the nature of the substituting groups. Generally. the higher the substituting bowoJogue the lower the carcinogenic activity. Small differences in structure may have very big effects on carcinogenicity. The first compound of this class found to be cancer producing was 1 : 2,5 ; fi-d (benzanthracene (Tig. i). 1 ! 2,5 : C-Dibmzam.hracone. y : m -D ii ae t. h y l- 1 2bonr.anfchrucone. K:r, 2. ( 'holon throne. One of tho most powerful is 9 : 10-dimcthyl-l : 2-benzarilhraeene (Tig. 2). Others may contain nitrogen, sulphur, five-ring groupings, or incompletely dosed rings. Cholantlirone (Fig. 2) is of interest as being a powerfully active carcinogen related to cholesterol (Fig. 3), and the sex-hormones ossl.nmc and testosterone (t'iy. compononis oi the human ho."' 11 U;(C ) I / \ /\/ 1 ! 1 H /N /'V ' (Jlmlcstiuol. Hi* fa, Other polycyclic hydrocarbon-, of tm- jo, have also been synthesized and shown i>, realized th a t these are also asyimm-trical in structure from the benzpyrenes and iron - Tho skin tumours produced by those compounds are truly malignant, and i; spontaneous and human eaueerri, 'That is tho real answer to the v.-rs significance of this synthetic Work ' Thai in multiplying the number or hydrocarbon of inducing cancer in experimental amm,dresults are consistent and rope,itrhie in.o in the study of the form of oecupati.a. i cancer, as well as in. throwing light on t! . of rancor in the Similar, body. Whether s', intermediates in .spontaneous human t.o relationship between thorn and body m ain . is a mutter for speculation But it is olo. must be opened wide--and everything wu 1 scrutiny. There ate, then, two grant reasons foi 1 relationship to the cancel- problem. Tim believed will be a relatively short-term p: l tho oil industry; and there is the possih- thoroughly organized reseaieh and study t It. may be reiterated that such a .sm all : etui be traced to actual cause that, it is of f clues should lie followed up inexorably I industries, petroleum is of small i m p m - t a n . m u s t, he repeated that litis relatively dyi importance. liM-mise of Ilie highly orgumV.ei. varying elieimeal nature of the crude oils , the widespiimd use of petroleum prodm-is " 1'he oil industr) has been eoneenied ii the following ways . -- (a) Occupational. (!) Amongst paraffin-wax wolfram, i ! (2) Amongst, hibrieating-oil mom ,i . (3) In the use of rutting oils. ,u , o w c r n a m i ) r H 'i'K i ' - i.' r m v< naked about it. It. is Jluoreaceiiee II. and Rieger, who collaborated with Cook, all strongly fluorescent and possessed similar position and distribution, Ilore having to wait for the results of biological upv mouths or years to complete. CJontliis means of control eventually resulted ng Ihe chromatographic, in the. separation I This has a closely related structure hich, though itself inactive,, has a similar partly m the visible. This synthetic II from which nearly all the highly active ind are derived. 'h fluorescence acoompanitw the general 'donging to this important carcinogenic between fluorescence and carcinogenicity, xnogeus which arc not fluorescent ut all. hydrocarbons of this kind are largely use,--as is seen from 1 : 2-benzanthracene cence in general which is characteristic, it light, hut the analysis of the spectrum n mind, since as a result of Rieger's itnzations have sometimes been made and ils and other materials, to use (luorescen.ee city and us a guide towards the use of ivcs of 1 : 2-bcnzanthra.emo which have -a, others only slowly active, and others s largely on the position of substitution tii.g groups. Generally, the higher the aver the carcinogenic activity. Small very big effects on carcinogenicity, lass found to ho cancer producing was 2) )-Dimethyl-1 : 2- it/,an thvnrcno. F ig. t. Oho1an Uiroiits- 10-dimethyl-1 2-bmrzar.thracene (Fig. 2), jili'ir, five-ring groupings, or incomploloiy . 2; is of interest as being a powerfully olesterol (Fig 3), and the sex-hormones u ' 1,1) F.S V rP O X M K N ' 1' V . f'W O K S i I N I ) I'l.T I'lio r.K ' IM 2*11 coKtrone and testosterone ( b y !'), all of which are, of course, normal com ponent of the human body. ;(U L lid ' < HjG J I /\ A / ` o M / \F \ /" ii.jfi .. Oil t ' / \1 7 l t 30 | ; d /\/\/" I ,, I i i. i l I \{/\/ '*/ (`hoAiorol. H ()/ V \ / Oefllrono ()A /V iristosterony. Km. :). Other polycyclic hydrocarbons of the phenanthrene and ehryseno series have also been synthesized and shown to be carcinogenic, but it will be realized th a t these are also asymmetrical ring compounds, not dissimilar f in structure from the benzpyrenes and benzanthracenes. The skin tumours produced by these synthesized or imturnl chemical compounds are truly malignant, and indistinguishable in nature from spontaneous and human cancers. That, is the real answer to the very natural question of what is the significance of this synthetic work? There would in itself be little point in multiplying the number of hydrocarbons and other compounds capable of inducing cancer in experimental animals. B ut the mere fact th at the i results ate consistent and repeatable may have the greatest importance in the study of the form of occupational and generally environmental cancer, ns well as in throwing light on the course and ultimately the cause of cancer in the human body. W hether such substances are concerned as intermediates m spontaneous human cancer, or whether there is any relationship between them and body materials of apparently allied structure 1 is a mutter for speculation. But, if is obvious th at here is a door whicti must be opened wide and everything within subjected to the most careful scrutiny. There art;, then, two great reasons for the study of petroleum in its relationship to the cancer problem. There is the attack on what it is believed will be a relatively short-term problem--occupational cancer in the oil industry; and there is the possible application of the results of S thoroughly organized research and study to the cancer problem as a whole. I t may he reiterated th at such a small proportion of nil human cancer i ,f can bo traced to actual cause th at it is of the highest importance th at such clues should be followed up inexorably. In comparison with many other industries, petroleum is of small importance in cancer causation. But it must be repeated that this relatively slight connexion may he of great I importance because of the highly organized industry involved, the greatly varying chemical nature of the crude oils and the processes concerned, and f the widespread use of petroleum products throughout the world. The oil industry has been concerned in the aetiology of skin cancer in the following ways :-- (a) Occupational. (1) Amongst paraffin-wax workers, in shale. (2) Amongst luorieating-oil users as mule-spiruiors' rancor. (3) In the use of cutting oils. 242 A l ' t . u : HIS ViliONM IlifT A I. OAjNCUH A M ) PiJTROTiKUM. (b) li.vjierimbnlal. (1) As BolocUvo-solvonti extra-eta. (2) In (Tacked oik of low volatility. It lx not proposed to canmdor those subjects mrttilim or chronologically, ft will bo more to Uui point to look a t those regarding which them has been must discussion, Many of tho m atters of broader Interest will then arise in passing. B u t itrat it must bo pointed out that both opidomblogioaliy and experimentally those portions of petroleum concerned are within the higher boiling ranges. Ho far there is no suggestion th at carcinogenicity is directly concerned with the volatile low-boiling or intermediate products such ns gasoline, kormrino, and gas oil. Nevertheless, that does not exclude I,ho hydrocarbons which may be present in such {'motions. Benzene itself, under certain conditions, is not free from suspicion, closjnto tho fact- th at it is a chosen solvent of tile biologists for the application of carcinogens to experimental living subjects. At present potential petroleum carcinogens appear to be concerned chiefly with those feitotiora generally known ns i (a) tho wax distillates, and (b) the Inbneating-oil residuum*. Those, in effect, cover tho whole lubrieating-oil range, with a boiling point from say 300" 0 upwards, Tho range- would include the lownst-viscnaity spindle oils up to those practically non-volatilizablo a t ordinary pressures, like the heavy machine oils. It. is also to be noted th a t the Hat includes on the one side shale oil and cracked fractions which have been subjected to high temperatures for their fundamentally reconstructive production, ami on the other side iubrieating-oil distillates and residues which by premise have not been eheimeally changed during fractionation, or the alight changes in which have- been negated in the normal course of refining. The distillation range in both Manses would, of course, cover the possible occurrence of those carcinogenic hydrocarbons--naturally known, synthesized, or yot to come which have been referred to. PiUtAi'TJK Wax AiS'n Shams On,. * The light oils and wax fierivet! from abate oil have bug been recognized , f i as onuses of skin cancer. Bell in Edinburgh reported scrotal cancer of a shale worker in 187fi, and Volknnutn is quoted by Lettish as recognizing ' skin cancer as a result of shale and lignite occupation in Germany one year earlier. Dermatitis is known to occur amongst the shale-parallin workers, but | there is no record o f petroleum operators with pandin wax having been fi subject either to dermatitis or cancerous growths. * It is most likely, even in shale, th a t tire irritant or active constituents ' are not p art of the wax, which is paraffinic by nature as well as by name, f hut rather of the oily coloured components accompanying tho slack wax. 1 These are known to bo chemically reactive, and are not necessarily allied in nature to the crystalline paraffin wax. Indeed, Benmblum lias ex- " tmctefl from Blue Shale Oil tho same 3 : -I-benzpyrene as Book identified I in rottl-Uir pitch. { X I'AL CAtfOliH AND T'iWWLBtfM. '.tracts. volatility. these subjects m iatirn or chronologically. 5 >k at those regarding which, there has been ; ratters! of broader interest will then arise | i pointed out that both epideiniologioally ' is of petroleum concerned are within the u*ro is no suggestion th at carcinogenicity latilo low-boiling or intermediate products s oil. Nevcifchidess, th a t does not exclude present in such fractions. Benzene itself, 1 froc from suspicion, despite the fact th a t I logists for the application of carcinogens , nn carcinogens appear to be concerned rally known as : () the wax distillates, nuns. These, in effect, cover the whole j big point from say 300" 0 upwards. The * seosity spindle oils tip to those practically ; satires, like the. heavy machine oils. *, ? list includes on the one side shale oil 1 vo been subjected to hightem peratures } ictive production, and on th e other side lidues which by promise have not boon ionation, or the slight changes in which course of refining. j ,h classes would, of course, cover the | biogenic hydrocarbons naturally known, i i have boon referred to. ) 'ax and Shale O il . 1, from shale oil have long been recognized I . i Edinburgh reported scrotal cancer of a nann is quoted by Leiteh asrecognizing ! d lignite occupation in Germany one year ; amongst the shale-paraffin workers, but | operators with parafin wax having been If icermts growths. 4 p that tho irritant or activo constituents 1 i paraffinic hv nature as well as by name, f ompononls accompanying tho slack wax. 1 iy reactive, and are not necessarily allied j uffin wax. Indeed, Berutiblum lias ex- > same 3 : 4-benzpyreno as Cook identified *( KiO. 4. a UT.r> l<NVfR<'>Xl5N"l'AI. O A N C E R A N D TUSTHO) K U M >1 H U i-ST U U N js r h ` O a NOBXl. The occupational disease of tmilc-apitinors' rancor has attracted much attention in the U.1C. I t is indeed around mule-spinners' cunr.nr th at much of the interest and concern in petroleum carcinogenicity lias revolved. Its history is already a trifle obscure, but it appears to bo the case that Soufhain and Wilson in 1922 drew attention to the high inddorico of scrotal eaiicor in Lancashire nude-spinners, and th a t in 1024 Loitoh was able to produce tumours in mice by applying solutions of the lubricating oils involved. Mule-spinners' oanoov is a, skin, cancer, cpidomiologically associated with the occupation of cotton-spinning with the nude (Fig. 4i. Operators who succumb, generally do so after a long period of working under tho conditions prevailing -sometimes over twenty years, The disease may attack various parts of tho body, but like soot cancer and paraffin cancer is frequently associated with tho scrotum. Tho conditions of operation are of importance, and have been recorded by Dr E. M. Brockbank 4 who says ;-- " The spinner works bare-fooled in vest and overall trousers without any shorts between them and the skin. As tho illustration shows, he leans over the mult; to join or piece with tho thumb and finger tho brokon ends of a thread of yam . . . Tho scrotum constantly comes in contact with oil on the trousers, '('lie vast majority of men piooo with the left hand, and for this reason the left side of the scrotum is affected a similar number of times. . . . " Tho temperatures in the mule-spinning rooms are excessive, and may exceed 105 'If. Brockbank also quotes Home Office records (Table IV) giving informa tion on the incidence of tho disease over some selected years. T a b i .e TV. 1926 1930 1930 1940 1946 tsphmars anti plotters. 48,029 40,714 32,232 23,000 17,671 Cases per 1000. 1-83 1-75 1-27 1-78 2-03 Total ctifcioa. S8 82 41 41 36 Total donahs 20 21 12 10 21 Ho poiuts out that the increase in number of cases per 1000 in recent years is duo to the greater proportion of older spinners a t work, and the greater liability of cancer of any form to occur. Mahohestbb OoMMxri'JSJs ok Cancer. As a result of the observations of Southam and Wilson and tho work of Leiteh, the Manchester Corporation somo years later, in 1928, set up a large committee further to investigate cancer in general, and mulespiunors' cancer in particular. Experim ental work was placed under tho direction of Dr C. C. Twort and tho cancer research committee under the 2 2.E- 3 sr (<i 2 l -- ac; t - ? 3 5 S' E p I si = } ~ E rr~Zj r~ P > S P S 2 -< = =r p ' = s. ~ o 2 S' a < z"~=? ~ - S' i f =- -; 3 & s=. ' sP- l ~ rr<- t *< r i ft 2. 3 .< ** * =' - . o - IN | ~ " ? s s. 1 t-z.- - o' o s ~ E => r ~ - g *" VC ^ c f" I %\ sr ^ = 3 ' ^ y- =' 2 <2ciS 5 E 2 5T 5 sS ^ ' -- s 5-"? 2i l l t i l f* S'. 2 * --br. g~'-K s c S = r- - | ^ L? --o 2 i. i f = . ? -" 3 ? 3 ioh r-: jg r~ s 5 f? I' | 5 ?S C ^ j~? 355" I- Ey M" H a. ? s ~ - J5 =5 2!: ~*~3i. B rr x< 3 ~ 2; T* ~ M 3 * g s te ~ r: L p ? o Sr s*' hl . S <p5 =a* 5T-- ?r o E o ^ ' S. ^ i _= 't s s * 5 K '"' r*- S' 5? = ..' E =3 E -.5= " fi-l. = - 2 5 S 5 z. = >s 9- p " p | " g a. .p r -n 5> o E *< r s f | p 3 5-1 E5 S' i S '< c _ '3 ^ T\ ^ S \2y =~' -3 3^5 S 2 - 5 s O _. I E= =i ll E t *2 I 2 ; P2 5 - r 3 s 3 g ''A N fE U A M ) I'KTIIOIJII'VI. UT.D ' 'IV V llir A lh r - T i! MO IMS 9 I ik. Reports wore published annually, (dished in Uio medical Frets. These ii, and siip] mrted liis conclusions that, carcinogens present in the lubricating In view of the importance of the subject, the, validity of the Manchester Committee's conclusions were naturally closely examined. Data showed this specification to be unsound. For example (Fig ;>) in blends of paraffinic (Oklahoma City) and naphthenic (Gulf Coastal), isidwvd by the oil industry - notably oils, curves, and chock-curves cross the specification limits of rofraetivity ( hori'/.outal) and sp ec ific, gravity (vertical) m such a way as to indicate icriean Oil Company, and the Anglo- | that blends between -15 and 71 per cent in one case and between 29 and 71 per cent m the other are dangerous, whereas all other blends of the same Tee proposed a standard for mineral i stocks would be safe. Many other similarly collated data also indicated to choose lubricants which should he I complete lack of acceptability of the specification. In addition, it, was made clear th a t " extent of refinement, " the characteristic most likely to hue up with `` degree of carcinogenicity ' goes in the opposite direction to , the specific refraetivity/density relationship when applied to paraffinic oils.5 I By this time, however, it was over late. The too-much publicized JlancheKter Formula for " non-cancerous oils " had understandingly, but wrongly been widely accepted as the complete solution to the problem. This was unfortunate for several reasons : -- (a) The textile workers, the employers, and to an appreciable extent tho medical profession were being misled as regards the facte of the ease, and possibly lulled into a false sense of security. Blonds of oils such as those described wero by no means unlikely to exist in practice. ((>} Tho oii industry found the Manchester specification unaccept able, and many oil scientists felt th at insufficient, attention was being paid in the textile industry to priw ntim i by cleanliness, working conditions, medical inspection, change of occupation for workers susceptible to skin trouble, and so on. Those things were known, from the petroleum industry's own experience ( with shale oil and occupational oil dermatitis, to be of the first importance. * Indeed, paraffin derm atitis and paraffin cancer wore already jegarded in the .shale industry us being under control and largely confined to tho older men who had contracted them years previously. Also, results both h the U.K. and in the (7.8. A. in the control of cutting-oil dermatitis, 1C6NT STOCK 672 by systematic washing and other roguiurked forms of cleanliness and in 0 f>. the application prior to working of protective creams and ointments, were vers- encouraging. mic properties. The criterion was isolesccnt, and consisted of a believed ' and the refractive index and specific specification read : * icating oils should have a specific i the specific gravity is above 0-895, / 0-5589 when the specific gravity is Another point which seemed to euppoit this form of approach to the problem was that enquiries in other countries--including the C.fcS.A., France, and India failed to disclose the occuitcuco of occupational canoein their textile trades when working under apparently similar conditions and with similar oils to those in Lancashire. (r.) It, meant th a t insufficient, attention was being paid to tho development--or rather tho testing and use. of truly non-care mogetiie oils. I t had been apparent to many oil men th a t more drastic, refine nlvii.y is m eant M T *, where n. is th e a ment- possibly by solvent extraction, or by treatm ent with such agents .as might be expected to destroy the carcinogens, was the most mu bglit, and where d is density in logical approach to the problem as far as the lubricating oil was concerned, `M li ' E N V / E O T i l F V ' f W c>. M E ' ! A H I ; F'E T P O M II T O , (d) It delayed consideration of systematic examination of petroleum for the purpose of separating the actual cnreinogmw and study of their chemical structure and properties, Wa icrimk CoS' uIT 10>rs In 11)43--14- arose two m atters of some signiiieuueo in placing fclio study > of the carcinogenicity of petroleum on Iho right lints. The first was the 4 bringing to notice by Twort of the possible c a r c i n o g e n o r other,rise- noxious effect of iubrieating-oil uxtraete, which under war conditions were iii use as substitutes for extenders, plasticizers, and binding materials which could no longer be obtained. The second was an approach to tho Petroleum Board by tho federation of Master Cotton Spinners' Associations ami the Amalgamated Association of Operative Cotton Spinners and Twiners, asking th a t oils to tho Manchester l Specification ho made available to the textile industry, In making this request they quoted tho Manchester Committee as stating . . testing of oils from cotton mills for carcinogenicity has been practically discon tinued, as all mineral oil being generally used us pooled and is a mixture of oils, , . 'This, of course, was not nt all the way in which the Lubricating Oil Pool actually operated ! But it gave the Petroleum Board t.ho opportunity of summing up the situation, and pointing out th a t oils to the Manchester specification had not been asked for during the previous four years of war cither by distributors or users; that- such oils could undoubtedly have been supplied if wanted, and the Board was prepared at once to set aside oils meeting the specification in two ranges of viscosity--- despite the Fact th a t tho efficacy of the spocitieatioii was questioned. At the same time tho Ministry of Fuel and Power drew attention oneo more to tho necfl for the improvement, of operating conditions in tho cotton mills. Tlioao two m atters obviously tied up together. If, by solvent refining ocialrcsilnoocgkesnifcromthawn htihceh oluribgriincaaltinstgocokilss, athreenmtahdee-,retfhienedexotrialsctms uwsetrebomloeraes ( ho. This confirm ed with tho oil industry's past, views, and tho Petroleum ; Board arranged to finance biological testing and research on. tho mutter ! at Birmingham University, Work was initiated by Prof, Harwell Wilson and IJr J>. L. Woodhouse in the Cancer Kwtearoh Laboratory ju the D epart ment of Pathology and under the aigis of the British Empire Cancer t Campaign Committee, / After about twelve months' investigation and testing of petroleum extracts, interesting results wore obtained to which separate reference will be made. White On-s. ri Throughout the extended study of the relationship of lubricating oil 4 to mule-spinners' cuneor the question of extent of oil refining has cropped l up frequently. As far as the oil is concerned this has always been the i \ chosen aspect to the problem of tho chemist and oil technologist From quite early days Twort expressed belief in white or mo<denial oils being i the least carcinogenic of all he tested, sharing immunity in th a t inspect with fatty oils. Tho possibilities of removing reactive carcinogens from s mineral oil by earth treatm ent, oxidation with air or ehomkiaia, solvent H.' r.n - r \ v n ; , - \ v u , . extraction, acid trail men*, us-rv ,, T hat possibly was duo i.o mi,- i(1,, amount and expense of tin.- I, M,, perhaps in those most iotinurWi In the early days of llrtfi, in-w- , r- Oil ReSinory i Jrosip. in iHiitj-ucs t,,n n the use of technical or modd-mal a, im These oils aro selected petroleum ,h -i i acid or oleum. 'Flu; proposal was brought iv tft<, whoso advisers wore quickly alive u, i mended that, if a priuta f<iv,c , aw -mi genieity of such white oily they <. textile trade as spindle oits. Fs.-.j, , available was meagre. Movert in 1,-..^ of Labour and attended b;> rewv ,-n: trade, and tho petroleum m.luntiy, i and Power to make white oils avid firmed, despite the scarcity and do! Simultaneously, the Petroleum Bum subsidy of research work on the mine very limited information on whu-h tic W ith tho exception of ,t few moi : 1--U once again nothing happened 'or an, years. There wen* practically no demands for supplies -cither from c, In 19-18, however, the Master Spmtn called into being tho ftd hn<- (VuimMit-v sonta-tion from the Shirley Institute corroboration by Woodhotiso r>( Rum of white oil samples submitted by tin- Decisions were thbroou made by Spinners' Associations to ,finiKlKr<'i/.c practical tests showing l-hem io !un r s Such mill trials, curried out wiib j>`, with fatty oil, nil of comparable r ij-en-: and unexpectedly very little d (feicr power consumption. The ad hue aommilleo concerned h >. being brought under the control Ministry of Labour and Maternal Sum c W hite O il S i l t was remitted to the polnde-im a specification to cover siiilitb--- at,, This has now been done, ami the nrai Committee, by whom it may be p date. The specification is based pritiurl t ` VNf'l-'il W IJ P K T a te B U M fsystematic, examination of petroleum the actual carcinogens and study of operties. Co n d it io n s , some significance in placing the study on the right lines. The first was the 10 possible carcinogenic, or otherwise acts, which under war conditions were S plasticizers, and binding materials u> Petroleum Hoard by the Federation 011s and the Amalgamated Association inerts, asking th a t oils to the Manchester the textile industry. In making this Committee as stating . . testing of gonicity has boon practically disconirally used m pooled and is a m ixture is not at all the way in which the ed ! Hut it gave the Petroleum Board situation, and pointing out th at oils not boon asked for during the previous ,ntors or users; th a t such oils could wanted, and the Board was prepared jccification in two ranges of viscosity-- the specification was questioned. A t and Powor drew attention once more pointing conditions in the ootton mills, up together. If, by solvent refining its are made, tho extracts were more <s, then the refined oils m ust ho less lustry's past views, and the Petroleum 11 testing and research on tho m atter was initiated by Prof. Haswoll Wilson or Research Laboratory in the llcparta?gis of the British Empire Cancer 'estigation and testing of petroleum ibtamed to which separate reference io Oil s . of tho relationship of lubricating oil n of extent of oil relining has cropped 1 concerned this has always been the i chemist and oil technologist. From thief in white or medicinal oils being eci, sharing immunity in th a t respect f removing reactive carcinogens from dation with air or chemicals, solvent u i i r > : R t i v n m x v r f t v r A r a m o v v n < u i.ie rw , Ml extraction, acid treatm ent, wen* all discussed, bid nothing was done. T hat possibly was duo to the iiniiled testing IheiliticH available, the am ount and expense of the work involved, and lack of a sense of realism perhaps in those most intimately roru'oruod. i In the early days of 11)40, however, the step was taken by the Manchester Oil Refinery Oroup, in conjunction with Tivort, of definitely recommending 4 t lie use ot technical or medicine I white oils us spindle oils For mule spinning. These oils are selected petroleum distillates heavily treated with sulphuric acid or oleum. The proposal was brought to the nil notion of the Petroleum Board, whose advisers wen; quickly alive to tho logic of tho suggestion, and recom mended that, if a priinu Jn.t'.t.f ease could be made out for tho nou-uaruino- genicity of such white oils, they should at once be made available to the textile trade as spindle oils. Exam ination disclosed th at the ovideneo I . available was meagre. Nevertheless, a t a meeting called by the Ministry of Labour and attended by ropresenlaf ivos of other ministries, the textile trade, and the petroleum industry, the decision of the Ministry of Fuel and Power to make white oils available os textile lubricants was con firmed, despite the scarcity and dollar cost of such oils at that time. Simultaneously, the Petroleum Board announced its further financial subsidy of research work on the aubjoct at Birmingham to supplement the very limited information on which the docision had been mode. W ith the exception of a few more letters and articles in the trade journals, orteo again nothing happened for another extended period--nearly two years. There were practically no enquiries for the white oils and no demands for supplies either from consumers nr distributors. In 11)48, however, the Muster ,Spinners and tho Cotton Operatives again i called into being tho ad hoc Committee of 11)46, with tho addition of repre. 'I sontution from the Shirley Institute. By this time there was fortunately r 4 corroboration by Wood house of Birmingham of the biological inactivity \ of white oil .samples submitted by tho Petroleum Board. { Decisions wen; thereon made by tho Federation of Master Cotton \ Spinners' Associations to standardize on the H8 of white oils subject; to practical tests showing them to have suitable lubricating value. Such mill tvinlfj, carried out with plain white oils and white oils blended with fatty oil, all of comparable viscosity, showed satisfactory performance and unexpectedly very little difference amongst themselves as regards power consumption, Tho ad hoc committee concerned has since achieved an official basis by being brought under tho control of tho Factory Department of the i Ministry of Labour and National Survive. W h it e Oil Spec ific a t io n . I t was remitted to tho petroleum industry ropreaenUttivcti to submit I a specification to cover suitable white oils for adoption by the trade. This has now been done, ami tho draft specification is iri tho hands of the i Committee, by whom it may be expected to be published at en early i daTteh.o specification is based primarily on definition of nature and pro- A l t , ' . ! . K S M H ' V . H I i ' i r u , c >, N'S ' ll'- ' V S P I' W ' R O ) J O 1M. .!ur.(.i(m, and upon colour. It is recommended thus colour should bo <>(' from sffu'kr. d e rh 'd from ibllimm the highest standard known, ns representing the most drastically refined trout,ment B ich J'eus.mi'ig T i oils, and eonsoi|uunity those likely to bo the least, cm'ehirtgonieally iic U v e . selective .sohuom. Thow loiur,,. n, Later, whim further testing and investigation bus been earned ooi, ring-type compounds, which me1 u , si may be possible to relax t!so standard without danger. This joint eoptible const if,m-nts, no Uru Hr- l( notion of the cotton and petroleum industries, with the support and under oxidation for example, and is nu n- j... standing of the (ovcrimu.*nl, is a line example of eo-opcration for the oil. mromnis good. It makes up somewhat for the period of misunderstanding Tho materials tested i(t Uc ...u.. -.. and diversity of tuition of the past Expenditure of time and money, and derived variously from . - ultim ate cost oi the very spceinl oil eonoerued, have been no obstacle in dealing w ith this aspect of the fell disease. Venezuela (Colon, Lagundl.i-, i \ As far as can be seen at present nothing farther can be done as regards l! S . A , (t'ul.f Coast (West Beam the oil. Colombia, beTnhoerfeidsmoafye.elhinogwoevf esra,fehtoy,unibI ti'sineemnossnt,asgisn,caernedlyittoisbeossheonpteiadl tthhaertensohthouinldg < will interien; will) the campaign for cleanliness, for protection by means of 1 Hqufi'lor, Middle East (Persia), V, K, (Eakring). clothing and barrier creams, mid for better conditions of operation. The recommendation of the Joint. Advisory (Jommit1.ee of the Cotton Industry The solveid-extraction prowu-w-s , ,,i (M)-hr) for the adoption of autom atic wiping-down motions and non-splash ISoiouto), Kdelesmu (beiw.ol.'KO^). .uni ! devices is good as far as it goes, hut no layman can but wish th at mule I Altogether, twelve petroleum ixir.i spinning, with its attendant conditions as described by Ur Broeitbank, * over a ])enod of some twelve nmtilli eonJd be exchanged for other methods of spinning less exacting, tests followed, and gave sime-a id.wli oompurou by cheek-fosr.s with laim, T atty Oils. e.hemicidb ronnsdly m,ed u.j pis-.;.! ur Htatsments to the- effect appear from time to time in (he technical and trade Tress th a t animal and vegetable fatty oils are noii-inm ous Twort, has recorded all such oiks tested by him as being innocuous; hut- ho lias also pointed out th at oleic and lino loir, acids (width may, of course, bo present to an appreciable extent in commercial fatty oils and to a small extent even in wcll-rofincd nib) arc capable of producing non-mnlignnnt tumours in mice. They are also capable of amplifying the rammr-proouemg oiled s of certain chemical compounds. I t has also bam stated th a t when using asa-ino oil as a carrier for chemical carcinogens the blanks with sesame oiono were not free from activity.3 These m atters are mentioned, as the specification for white oils referred to may factually or tacitly permit compounding. In this it would ho in line with the observations of the Manchester romir.itl.oe. I t is well to realize, however, th a t there is no full eleitnniee lor fatty oils, and in view of the dilhcully of defining their nature, and their purity the author would industry. The resr.il.s varied (pmiilhui e, ri\ t, showed thru solvent refining '.emUs, \ cnttdaogeJW in Urn extra els. The - w activity than ..uiTeynnumg teal-rer pi(, matci ials already m use, ISTvt rHc-hre. should be used with eirmiin-.pei tn.i (specially avoiding continual bodily m Recently some attention has been di (`xl.nto.ts ns eoio oils in ft-hi(dries h>k products less readily obtainable. Tit , such recent use of extracts imu! n Is cancer amongst fonudiy worker's. Im possibility of all decoiuposmot- pi o ' temperature being wuemogeiue. suggest limitation of their use until further work has been done. All concerned would wish to express their appreciation to .Or 0. (k Twort for Ida devotion to his purpose, of ttlttnmating mule-sptmter' cancer. I'tra n ; ( The single-mindedness of Twort. and Ms co-workers--and of tho Manchester Committee as a whole -has been responsible, both directly and indirectly, for much of the progress made. In a recent paper by Dr (Jr.iieksh; i drawn to the possfole effects rr exp-.-, engineering pirocesses ; and m da iiiuiU O A R o iH o a ra io ia 'Y on' O n . E x t r a c t s . unities itiaebming. Under tlux: i"ri'uh folliculitis (in lauialitni of the lmu foils ! The work of Woodhouse at Birmingham on behalf of the Petroleum affected. Moreover, about eiw-fi.iru el Board, to evaluate the carcinogenicity of oil extracts, covered materials of one. of two kiiuh These warix w JI u. ( r\ n roci.miner.deil that ooloiu should bo of epresoiitmg the mewl (Intsuw.My refined to be the heist cnraiiogetiicnlly active, ud investigation has been carried out, standard without danger. This joint i industries, with the support arid undcra hue example of on-operation for the Hvlwl for tlu' period of misunderstanding Expenditure of time and money, and oil loneemed. have, hecn no obstacle in disease. i. nothing further can be done n regards on snags, and it is essential there should most sincerely to be hoped that nothing ir cleanliness, for protection by means of for belter conditions of operation. The isory Committee of the Cotton Industry tic wiping-down motions and ti<iu-s>pbih but no layman can but wish th a t mule litmus as described by Dr Brorkbank, hods of spinning less exacting i'TY Oils. from untie to time m the technical and t.ble fatty oils are nou-eaueerou.x, Twort him as being innoeuouK ; but he has also acids (which may, of course, bo present le.roia1 fatty oils and to a sirinf extent .tie of producing lion-umligiumit tumours amplifying the cancer-producing effects . using nosh mo oil a s a carrier fo r ehomicai 0 alone were nol free from activity.3 1 t.he specification for white nils referred * compounding. In this it would bo in Manchester Dommittee, Tt ts well to nil deal mice for laity oils, anil in view aliu'fe mid their puritv the author would d further work has bean done xpiess their appreciation to Dr 0. 0, iso of eliminating mule-spinners' cancer, d his co-workers- -an d of the Manchester espons,bk\ both directly and indirectly, v o r On, Exthactk. rmingham on behalf of the. Petroleum licit,} of oil extracts, covered materials u 'l.n m n \!M i;\'T \i ( w c ic u i s u m iTiiof.K i'M , > in from slocks derived from different m ules by various processes of solvent treat incut. Much treatment, is a process of physical extraction with selective solvents. These remove the more aromatic and naphtheuicring-type compounds, which include many of the more chemically an cc|)tihle eorud.iUieiibs, so th at Hu* raffinate is much more resistant, to 1 oxidation for example, and is more paraffinic in nature than tho original t, oil. Tho materials tested at Picriingim.ni were all products from feed-stocks derived variously from , - Yenfizwla (Colon, Laguullus, Concepcion, and 'I'm Juana), li.8 ,A . Gulf Const (West Beaumont.), Colombia, I Eqvador, M iddk tiaM, (Persia), U. K. (hiakring). This solvent-ex traction processed wmuorned included Duosol (propane/ Solueto), Kdolemut (bonsMil/SOj), and furfural. ( Altogether, twelve petroleum extracts of different kinds were tested over a period of some twelve months, A second series of confirmatory tests followed, ,md gave ti[most identical results. The first series were compared by cheek-tests with known carcinogens and with certain okorcicals normally used ns plnstioizons and e x te n d e r in the rubber industry. The results varied quantitatively from one. material to another, but showed th at solvent refining tended, where they exists <1, to eoneoniralo carcinogens in the extracts. The most active wore lower u> biologies.' activity than corresponding coal-tai products and less noxious than certain f smhaotuelrdialbs ealruesaeddy winituhse.circNuemvseprtehcetlieosns, aitndwasunadpeprarecnotnttrhoalltemd iecnopnrdoidtiuocntss*, especially avoiding continual bodily contact Recently some attention lues been directed towards the use of pelt oleum extracts as core oils ca foundries, taking tho place of linseed and other t: products less readily obtainable. There nan be little coimuxion between such recent use of ox tracts and a believed above-normal iruidenee of cancer amongst foundry workers, but it draws fresh attention to the | possibility of all decomposition products of organic m atter .it high tem perature .being carcinogenic. Ci/'fTINO Oii.fi. i In a recent paper by l)r (Jruieksliank and Prof. Squire ' attention is drawn to the possible effects of exposure to mineral oils of worketx in ( engineering processus; and particnlarly to the use of cutting oils in auto i< matic machining. Under these conditions workers are .suaeep'.ibie to oil folliculitis (iul'.airiation of the hair follicles), and the groat majority become affected. Moreover, about one-Hard of those examined contracted warts of one of two kinds. Those warts arc of a type known amongst tar- I1 T SW) HVr.O , TINVlKONMK'ftM, CANOJ:'K I'lkTllOT HTM ! workers and mulo-spinncrs. There were m addition dome, oases of pro- j cancerous akin condition and one of scrotal cancer. These observations may have to be regarded as warning signs, and f certainly call for study and amelioration where possible of the conditions j oi operation. Ll seems to be the ease Unit whilst a little of the cutting ' oil may be oxidized at the tool edge, the considerable loss of oil known to occur in use is due to the formation of very fine spray which deposits on t the surroundings, including the operators, as a thin film, The initial in- flammation is mostly on the hands and forearms, but clothing becomes j charged with oil, and the general conditions in this respect are not dis- i similar from those m et in muIc-spinning , The conolusion to bo drawn is th a t if improperly dealt with continuous 1 exposure to cutting oils is a hazard. This is supported by certain epidemi ological d ata and also by biological tests. Magnification of the effect is | ' undoubtedly caused by irritation from clothing, injury, and abrasion from , metal particles, and in this respect falls within the class of' action of oil and other occupational dermatitis, to the avoidance of which much attention is nowadays paid-in factories. In this connexion Cniickshswik and Squire urge stricter methods of prophylaxis--reduction of actual skin contamination by oil, improved f anti-splash devices, and use of more suitable clothing; higher standards y of cleanliness, organized use of effective barrier creams; regular medical inspection ; and attention to personal susceptibility. To those interested in the nature and use of barrier creams a previous paper by Oruiokshank 7 on the subject of their evaluation may he roconi- j mended. As protective^, the soapy type of oil-resistant, barriers sewn ! to be of limited effect, and have the disadvantage th a t when after a limited I time they are penetrated by the mineral oil they give no aid to subsequent 1 removal. Greasy protectives, on tho other hand, rapidly mix with the > contaminating oil, but. do assist subsequent cleansing, fn view of the dubious nature of some of the protective components, it is clear th a t a groat deal more, work is required on the subject. Crack ed -oil P r o ducts. Modern refinery practice is largely concerned with the reconstitution of i \ petroleum hydrocarbons by moans of heat and catalysts. Under the f ; conditions of cracking and reforming, most of the now products are mole- enlarly relatively simple. B ut there is always a small proportion of heavier materials formed by re-condensation and polymerization. These, when distillates, may range in boiling point up to the gas oils and light, fuels. ; They arc preponderantly aromatic in character, and having been sub jected to heat treatm ent are not readily susceptible to heat, Their $ molecular-weight range, for example M.W. 230-250, would include th at , of many of the hydrocarbon carcinogens previously mentioned, in view of their nature and mode of origin it is not surprising th at biological testing ( has shown some of thesis fractions to possess carcinogenic activity. This | has resulted in the, suggestion being examined by tho medical section of the American Petroleum Institute, to which reference will he made | later. d , i,, , 0 i'O i N[, ,; i \ Insliluk of /'clmku/n Ih.<<'tw!` , Tho work sponsored <t! I'.in.im J ,. ,. started by biological h>Mm.< account of this work is u.nouie ,i j It had been determined by !>u- . 1 th at work on the earcmogeiiiciK m . m ental basis as soon as pi.-s-J |,. j the necessary funds, and an.newt,,, Cuivorsity to undertake the l>i<>lum> Timao arrangements were well nud. t dissolved. Amongst its last ,tct-iviti * the Ministry of Tim! and i'ow.-r. an].,, accept responsibility for c o n i i n e . , sum to initiate the research, it w,.-. when needed, would be forth. <.nm f. i The institute accepted the n-sp-u.. formation (under its Research Cumm,, which the author has the honou: to n The Group, consider '.hut work applied or ad hoc nature, but on end. active components present tn peirol, As there are hundreds of ddf,"~ri!i ,, crude petroleums, it is nec.-s-ors o choice. This choice is go\ erica! ',i\ . {) Difference of type and disk. (b) Importance in extent of pn (c) Content of Inbriailing-oil already indicated, had oremvod n (d) Supplies being the eunijdoo (e) Authenticity and repeat;t!u Medical Hkscwch Council. Quite soprraudy, as a resuh of tin a genioity, the Medical Research Coutn miitee with tho terms of' reference . " to inrJato and carry out re;v-.u mineial oils and compounds of combined in use," The Medical Research Conned, r .-I,, Privy Council, and as such pot-sesst- , upon such action. Tho Committee thus formed is ... in nancor pathology, the rhet u.-,1r\ m and petroleum technology. Th \ 11 nom inated representatives h> ;Ht<-un - The M.H.C. Committee. ivmks , .ANCl'K ISO I'KTRfif/HI'M, -ere in addition some cases of jireirotril cancer. be regarded as warning signs, and 'on whore possible of the conditions o dial whilst a. litllo of tho cutting the considerable loss of oil known to if very fine spray which deposits on tors, as a thin film Tins initial invnd forearms, but. clothing becomes iditions in this respect arc not di* 'gif improperly dealt with continuous Phis is supported by certain epiderniests. Magnification of the effect is clothing, injury, and abrasion from ills within the class of action of oil to the avoidance of which much d Squire urge stricter methods of n contamination by oil, improved suitable clothing; higher standards ive barrier cream s; regular medical susceptibility id use of barrier creams a previous of their evaluation may be recomtype of oil-resistant barriers seem advantage th at when after a limited d oil they give no aid to subsequent other hand, rapidly mix with the [iient cleansing, ne of the protective components, it required on the subject. rrtoDroTS, oncemod with the reconstitution of f heat and catalysts. Under the most, of the new products are molealways a small proportion of heavier ur.d polymerization. These, when up to tin: gas oils and light fuels, character, and having been sub'uiiiy susceptible to heat, Their W.W. 2.30-250, would include th a t ns previously mentioned. In view lot, surprising th a t biological testing losses* carcinogenic activity. This examined by the medical section to which reference will be made r w'l.o : rKvu-.ii iHKXTir, ij i s c c i i and ffmim.i-;uAi. 251 O ruaiNjzatiox of R e s e a r c h . t i i 1 i r ! it 1 i Iinstitute. nf Petroleum Research Group No. 2. Tim work sponsored a t Birmingham University by the I'utrotamu Boon! started by biological testing of white <>iU and petroleum extracts, Ah account of this work is coiiijunwl in a paper by Woodhous and Irwin.* ft had been determined by the Petroleum .Board's advisors, however, th a t work mi the carcinogenicity of petroleum should be p u t on a fundaniBntftl basis as soon as possible. [for Una purpose the Board promised the necessary funds, and arrangements were- made with Birmingham 'University to undertake the biological side of the research work involved. These arrangements were well under way when the Petroleum Board was dissolved. Amongst its last activities the Board, with the concurrence of the Ministry of Kuo! and Power, approached the Institute, of Petroleum to accept responsibility for eimthiuation of the work, and offered a substantial sum to initiate, the research. I t was implicit th a t further financial support, when needed, would bo forthcoming from the individual oil companies. The Institute uccoptnd the responsibility, and implemented it by the formation (under its Research Cknnmittco} of Research. Group No. 2, over which the author has tho honour to preside. The Group consider th at work embarked on should not be of an applied or ad, hoc nature, but an endeavour to separate and identify the Active components present in petroleum and determine their properties. As there are hundreds of different oilfields and many hundred difforen! crude petroleums, it is necessary to be realistic and make a limited ehoteo. This choice is governed by (a) Difference of type and distribution. (b) Importance in extent of production. (c) Content of Iubrieating-o.il fractions, since carcinogens, already indicated, hud occurred in the heavier distillates. (d) Supplies being tho complete and untreated mules. (e) Authenticity and repeatability of experimental supplies. where Medical Research CkmncAl. Quite separately, us a result of the attention paid to mineral-oil carcino genicity, the Medical Research Council a t the end of 1948 set up a Com mittee with the terms of reference - " to initiate and carry out research into tho carcinogenic action of mineral nils and compounds of other origin with which they muy be combined in use." The Medical Research Counoil, it should be explained, is a body of the i IVivy Council, and as such possesses all tho powers necessary to embark upon such action. i The Committee thus formed in of high calibre, and includes specialists in cancer pathology, tho chemistry of cancer, biological testing, statistics, i and petroleum techno'ogy. The various ministries concerned have also nominated representatives to attend as may be required. i Tho M.R.C. Committee works closely with I,lb Research Group No. 2, I- ! AMI LK A N D I ' M T R O I . B U M . I l Lb i o w i !>>,i i i o . \ r w , <i n ' l i o u \ v o p i n ' i ' i i H j ' r u . itive. The piogramme embarked upon witi) ultrasonic oil emulsions are an indication of the existence of ameliorativo properties in some forms of petroleum, or even in the petroleum oiu-<'inogens tkomsc Ivex. the, lu s t instance to skill can cer, whilst, ns, roeted l>y Prof, .Squires at, .Birmingham, iftd. l reeled by Prof. Cook at Glasgow, ir, ) `Search Group, No. 2. f choice of three c ru d e oiks is confirmed, r their fractionation, The- oils are, il Co.), Kxtensivoly produced Middle, much used in the TJ.K ; of paraffiniomng hibrioating-oil fractions. J.'Cj't. ( i'Ci'-i. - Ilsic|ser, W. Ktn'mmmoiiLil t.tetccr," tots. Uovs. Primiitj- OlRec, PHS, - i-'ufi. Peokvnll. PltU'iii`i,.jeal Ob.scrvatiomL.'' n7;>. 1 ('cult, .1. W. C`Uemilry mtd Oiuteei-," Ktiynk liraut-ulu of (tlic.niistiy JUMP). ' Hivnklmtik, K. M, ' Mnle-h"j)imn>r.iJ>f.'nneor," tircchuro, P.MV. Ault I. it, ,). SI. " :>|)M'ifHS rofmetiviry sunk eftreinogcniotl,? of miwsml hihike.it icy cite" J, im t. t f J m . , liK, 84, m . * {.'otiokshsusk, C. N. J).. and Squire, .1. M. " Skin in flm empiiwriiiy imimv ry from the use. of mineral Ml." lirit. ,/. hul. Mot., IttiM), 7, I -i t. (.Tisiefciimnk, C. N. I). " Evaluation of side eloimsers uiul protective creams for workmen exposed to minoi'iii oil,'' Urit. J . hut. M ni., UMS, 5, 20k. 8 WootLltoiiao, i). J,,, ami Irwin, U. /. llf/ijiniie (in the press). ' Niivyiulomwkii, SI. S(. `` Ullrasuitie Nniliiinn eimslsions." N uuku i Zhisu, 1'Jlfi, {}), 22- 3; J. h u t. 1'elrnt., I(M3, 32. 155A (Abs. No. o2S), 3tiU.\ f,Vi, il.VI); icla (Shell Petroleum Vo.). 'Typical . i wn history and producing well-known I'aJioleum, 1!)!(!, 9, Let. id-Vonliwtnt {Hocon.ff-Vit&w>i,m Oil, (Jo.). Sonlincnt distillate, bright, stock, and avc been received, and initial fraecionaloruton Research Centro by distillation /armnii and steam. All fractions are lueod. and the course of subsequent i I lotions will be by methods least likely active component present. The exact, ffernienl and petroleum interests. I t is Kids to those known for following the r arrinogenie components and effecting I iislied with the American Petroleum arrangements nmcle for the exchange e A.P.L is embarking on a substantial ,g visits of workers will be, arranged, being done is commensurate with the i; ,nd of medical research, ft, is sincerely Its leading to the elimination of environ- i iay be concerned. Also, th a t kuow.odgc laths leading to th e understanding and it left an exaggerated estim ate of the ml effect is small even m the small ee.i. Attention should bo paid more ro m thm ous contact with oil, than to the to " touch pitch without being rlotiled," tv poisons m industry, ii, might oven be, th at the- persistent, essful treatm ent of malignant tunioura