Document np9m4e4Y3oEXqmDqgpw8QaZD2

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 0000 DOC#: API211 DOCUMENT DESCRIPTION: Book Excerpt - Environmental Cancer and Petroleum [Article 3; Environmental Cancer and Petroleum] ARTICLE JL* -JB..JBL. Bt -JBk. JHL- -JHmwhm 3 Environmental Caner and Petroleum 1 lwucoi-jiUc-ir, i-KorKuTis . rm i. Will Hi-iningeii O) valuable clisenssiom ikjke/dhell 1,abora.toisum-A ms torda ni '(`enees, k, It. VV. ' A.MInllmn; arid gt'oluelton 8 , S3. ' lim , 44, 33". Mwii.. l!U(>,13, A 101. Inti, hvlia. Dec. 103(1, 33, 1. <52. K N V IR O N V fH N T A L C A N C N K A M D 'P H T ItO L lC U M .1' By Dr.-Cor,. S. J . , Agld, O.B M., HI C (PaH.I'mide.nt',. | Mohkx industrial nitiliziUion lias; brought, ill it train many added I dangers to mankind, Not lito loa.it of thenu aro tho oectipnitoiial diseases resulting from exposure to eoiuliliona arising in the course of manufacturing operations. Sometimes such adverso atier is come from tho absorption > <4 defimlo poisons. In th at ease stops can bo taken for tho purpose (' iimelioroliiig the environmental conditions, l.n any ovonfc fclio course of the specific poisoning can often ho followed and knowledge built up for the prevention and treatm ent of the ailment concerned. T hat is par. ticulsriy tho case whore tho poison is rttcogtthaible and is quick in notion. Whom the effect is slow or n. lengthy latent period exists, culmina! mg in sudden and often apparently imrelatod illness, recognition and control \ of tile disease is more difficult. T hai is gonomliy how if happens with (mviitmmental cancer -with cancer indeed as a whole, where the initial impetus given to the uncontrolled cell growth which constitutes the disease is oil on unknown because of tho long latent period which follows. T hat is regrettable, for, with few exceptions, the omisos of moer so far discovered uro of external origin. I t is, unfortunately, also true th at at the present tim e only a fraction of l per cent of all wince,ra can be traced to known cause. To bo able to trace tho origin of any cncer is, con- seijiK'Ully, of the gmiles, possible value in the building up of our defences 1- in ivhaf the whole world is rea Using in ihe proales!, bailie oi nil iiine which man lias luid to wage. It m For niich reasons tlrnf, the appearance in this held of the petroleum \ ituluslry is to bo whole-heartedly welcomed. The oil iiuhiKtry is tho most highly organized and nuk;!, seienUfically controlled of all the world's great industries. 'The fa d th at its direct participation in I,he causation of cancer appear* to he sumll is of little account compared with its resources for the collection and recording of d a ta ; mid in particular its ability to trace oleefs lo identifiable materials, to conditions of production arid to niclhmls of handling or application. in order to show how tho oil world is helping to-day, and largely in i (Jreal Britain, in establishing a link between etume and effect d feast in occupational or environmental ancor, it is neces-mry lirat lo sketch in i aihned btoacpkrgorcoeuendd thoefr'epfrroovmedtoorfisleusppaercttiecdulacraucsaesso ooff etnhveirhoyndmroecnatrabl ocnasncaenrd, their association with petroleum and its application, 4 The inUior's position must be made idear io preven!, any misunder. i standing. Me is not u medical irmn or it biologist, and his nssociatiim 1 whoit Ihta(sIdhselspuebdjetcot irsepthraets;enotf nthileopiletteroclhenuomloginisdt.ustHiyo,wthervoeur,ghfor(hmeanInydiytema.rs i of Petrofomn, the PotroImim Board, ami tho Ministry of Puol and Power, > An malt',? to tho N orthern Brunch ut tho In stitu to of I'utroloum, Ja n u a ry 17, 1930. . 2 5 i s '-i 5 5 ;r : S-, c ^ O ~2 CH? O f ^ s s -l ~""" *s'". -gE - S O ' I of f rp'T- sr Z "- tr _ -< ! ?y S3 OC 4 I I K L e -- O s =r. sr r ~. -S 2 ? sC C5O S-- C -c f ~ /* . 1, l IM. 1 ,0 ! i-.111111. 1.1 ..I ns with Govern men I. and other bodies can, therefore, discuss the subject with but must emphasize Unit his specialized UHLS o f Oa n o e r . carcinogens arc generally either physical sir.11 include ft , y-, and X-rays, and , and is continually being extended. >pi oxiinately as in Tabic- 1. T im e f. io. matic .iinmi's, Anilirm K rolo Polycyclic hydrocarbons t OnHion block, T a r mid pitch mtiiin oi l." fthuto Oth M m s rn l Oil* limcono oil. Cir-io^oi-e dyes * trogc-as 4- lictin g (` vidonec. flieir chronology of discovery, with notes rgnn.a nfleeted, and th e nature of exposure. Table 11 After Hu-P'.m) Wirii-'i, \ i 1 j iiiiluro 01 exposure.*' sSkifHKfKS'tmtO Off .{dmursr-YvM-t.hpti) j Sion One., piiv , ! Sic <t Oec. (Homin','tin! -tliiiUi } nil : Skm Ofc, 'id !![ H' - Kkm Hkiti OC'J. Odd. Stem O(?. K\iU)b)) DhhUlov On*. (tfrv imimiry) * Kfuu OlY., IHWI. b<irttn.U, find r.ladfli'r iSww` iiutriD hnv. ts;r, Oct.. mi'll, hrnrock I k One. ; Mouth Habit- <tralia. Mtiiny) UiU UCIhUd. i.ivci idiv, ([Hivoly tlkds, ( I Scruma Skin Africa t-i> O cksc) Occ, .ncd <iml Wilvm Oeo. (mu!*' sj/unt'ii't <j Beisivwo : SUn Oec, l lionc itKMTCw 0 <M, * dnticsnmbii i hums O*'o ; Done Ore >-uc:' * 1 hup, Ore 1 ,\^>| simtst!, 0(*<5 lunp . OlOM. l.miR Ore. i ! uni Liuii' Ore., ired Oer. j v. =- unvhomui'nlal; med. *medicoI. Ai'i.n ; n 'lH 'i'iu ii'.'.r u eweft'u axp in- ru o u ir'i Important and iiitetv-fing as are many other of the forms of envina:ment-r.-l causation, those tabulated vidiidi have a part culm bt-aing on our problems are soot; panditi), and shale oil; pitch, tar, and t.,.r fumes; benzole, anthraeone ml, and creosote; anil lubricating oils. Attention is directed to the fact th a t, with the exception of " lubricating oils," which in any ease is a vague term chemically speaking and is largely 1 he subject of our special interest, all of 1host* organic materia Ik<>r individual chemicals are recognizably aionmtio in nature oi have been formed under conditions of heat, which presage their content- of such substances, This applies even to the so-called " paraffin ml," shown by Volkmann m 11175 to be tho cause of cancer amongst worker in the lignite and shale-oil industries. Tn general, it. applies also to the organic chemicals on (he outskirts of our province, like the azo dyestuffs and tire aromatic amines The original observations from which our present-day lines of enquiry emanate are those of the co.ebratecl surgeon IVroivall Pott, I'MiR., of St. Bartholomew's Hospital, ami recorded by him as far back us 1775.2 His diagnosis has already been quoted at length by Prof. J. W. Cook in his important address to the Royal institute of Chemistry on Chemistry nurl Oiinoeiv' ft refers to Pott.' recognition of chimney-sweepers' cancer ns a specific disease, concerning which he says .-- " It is a disease which always makes its first attack on, and its first appearance in, the inferior part, of tilt; .scrotum; where it pro duces a superficial, painful, ragged, ill-looking sore, with hard and rising edges. Tho trade call it soot-wart. . . The fate of these people seems singularly hard; in their early infancy, they arc most frequently treated with great brutality, and almost starved vt-k cold and hunger; they are. thrum, up narrow, and somotimch hot commies, whore they are bruised, burned and almost suffocated; .rid when they get to puberty- become peculiarly liable to a most noisome, painful and fatal disease. " Of this last cirenmsfa-me there is not the. least doubt, though perhaps it may not have been sufficiently attended to, to make it, generally known. " The disease, in these people, seems to derivo its origin from a lodgement of soot in the ruga, of tlu; scrotum .'' This tremendously im portant observation lay practically dormant- for one hundred years. Reports then began to appear regarding skin and other forms of cancer in workers connected with the coal-tar .ndusliy. These, together with reports from the sha-io-oil industry, and .aier the mule-spinners' cancer " of the cotton industry, indicated the existence of industrial, or at any ruto occupational, origin of specific forms of cancer. Since 1915, when Japanese workers first used modern biological technique for the laboratory examination of causative agencies of cancer, there has been ovor-expanding observation and recording of data connecting actual things, frequently chemical, encountered in tho industries concerned with observed incidence of cancer. Thus, in the coal-tar industry it- was pro gi'Cbsively shown that raw tar, and then particular fractions boring above 400 0 , contained the eimiinogenie materials which were being ,sought This was quickly followed by the- recognition, due to thou- freedom from z.ih Altai' , Kr.'-HlDN.HIiNTAIj rM.VfTOK ANH PKTKIH.IteM. nn.rogon and sulphur, th a t tho most active bodies e.>nrertwsd wero m fact hydrocarbons. BiOLoorcAr, Tms'rrxo. it is ns woll a t this stag to explain tho test procedure unerI by the biolngiots in determining tho extent and course of mnwmrunn activity. The tests arc made on living animals- elthilly mice, rats, rah hits, guinea-pigs, logs, and monkeys, The most extensively employed are mice--partly because of their aiweeptibility, partly because of the relative rapidity with which results enu bo obtained. Tho question m ust arise in the minds of oil men, or scientists in other spheres of training and activity, whether the disease <> induced in animals is the same or similar to human cancer, anti whether the effects are or are not generally otherwise comparable. Also, in respect of the repro ducibility of the tests, their quantitative sufficiency, and the. satisfaction by statistical procedure of elimination of other known or unknown conditions which might affect the conclusion to be drawn. All of those matters ate of extreme importance in biological tests in a tray much less known In the chemist and physicist, whoso aims to produce like results from like conditions arc comparatively hnplo in the m atter of choosing tho conditions. In tho past these points greatly eotmoniod those oil technologists who were drawn into consideration of tho problem of carcinogenesis : they have satisfied themselves th a t the procedure is standard and fully accepted ; flint the stand,a ids are .scient.ifiraiiy high--th at is, they are fully organized in detail and understanding like those, for example, of tho methods of the in stitu te if Petroleum. This im portant m atter might bo summed up to tho lay technical man by .saying :... (a) The results are. gonorally repeatable and reproducible, liven if there wore nothing else to the procedure, this would constitute it a valuable observation and non-committal test. (ft) The pathological effects produced aro constant, and closely similar to those of spontaneous and human caueor. ' (c) Difference of susceptibility or, as wo might say, the. response, of the various animals is recognized; and in the event; of checktesting being needed animals up to and including the primates aro available (Table Iff), Testa on mice, as being tho first, greatest, and best-organized screen, aro therefore vary im portant. The great laboratories use mice by tho thousand. They are bred from constant, suitable, trains, and are used, or should bo used, a t the same approxim ate age and condition of health- -and, of course, fed, housed, ami generally looked after identically. In a modern laboratory they are, as test materials, approxim ating tho standardization nf uhoruietd tost reagents. Olio aspect o! tilts biological test technique to which attention needs constantly to In* paid is th quantitative or statistical aide, liven with the quick-living sous, a series of testa requires dimit a year for com pletion. This is a big proportion of n mouse's life. It is necessary, there fore, to use enough mice for any test, and a t the rune time to know u:i i> Pp/J! Agent ! <IfiCtu Wool 1 i>km I bung Shiite oil j Skm . I <uug l-'itch and tar Antliouione oil Imbricating otta Creosote Bouzolo Tar fumes g-NuphUiyianum. ! Skiu , Skin i Skin Skin . Bone mu rrmv i f.mig Btekler i; it.i.,1. ,U. ........ Mon. .M,,!.... ... MohMem.,. T1iJ!.*`at Mhum- * * * C'ottihrf sufficiently the past history of ihoir sir., all the natural ills to which hey are p: required for the tests, extrapolation .if m when tho quaiditativi, factor is found i, ns a result of starting out with inxiiMic: > some experimental disaster. Bin ,->uvi.\ for th at matter, can obviously b<> verv d.i th a t biological testa must bo conducted m, ; care in respect of such conditions as Till-; Oakoini'..ir II. Tho recognition that ext.nta Ir-mi . tars worn fclieirwolves carcinogenic .-.tine, 1 single chemicals capable of producing me the pioneering work of Bin lirncst Kenu produced tars was important by directtn 1 aromatic hydrocarbons, and oitemiraidri.j I causes of coal-tar cancer. Kventnally, in tracked down in coal-tar pitch .t .^inmgl; benzpyrene (Fig. I) From tons of pi ^ g of the material. 1 j A t -I - ! I-, ' < The tracking down " of this livdioom Inis mote than academic interest, h Al, C \ t - ( ' K K A N I ) F K T t t O I A I l ' M . 10,-if; active bodies concerned were in fact | llOAf. TKSTJIiC!. 1 explain the tost procedure used Uv the mit, and course of eanet'rous activity, g auima's --chiefly mice; ruts, rabbits, The most, extensively employed arc eopt/ibility, partly because of the relative i obtained. ; mind of oil ri'pn, or scientists in othor vhether t.ho disease so induced in animals . . cancer, nnd whether the effects are or i parable. Also, in respect of the repro- j ititauve ,sufficiency, and the ,satisfaction i| uination of other known or unknown j: i conclusions to be drawn. All of those i: ice in iiioiogica! tests in a way much ; physicist, whoso aims i,o produce like comparatively simple in the m atter of y coucoriiod those oil technologists who "t if the problem of eiu'cumgcmesis : they procedure is standard and fully aonoptod ; > iy hig'r.--that is, they are fully organized * these, for example, of th e methods of important m atter might bo summed up %' - Uv repeatable and reproducible. Even I the procedure, this would constitute it " irs-nomuut'.al lest, j tt produced arc constant, and closely I us and human cancer, .litv or, as wo might say, the response, ' icognized; and in tho event of check- j ; up to and including the primates aro j ,, greatest, and best-organized screen, are I rat laboratories use mice by tho thousand, ,{ able, strains, and aro used, or should be i and condition of health--and, of course, j fter identically. In a modern laboratory 1 tlimiting the standardization of chemical ' i est technique to which attention needs ' < ntitativo or statistical side, liven, with j of tests requires about a year for com- , of a mouse's life. I t is necessary, there- l V test, nnd at the same tim e to know \ r t , P ' UN \ I H O N M I ' N ''Al , < ' A \ l ;K I! -\ M ) t' LCTIIOI . K t AI Ti!) 'i'Afil.lS IH. cf Occupational Ijaiaci'o in ,-i nconic. Agoni Organ, Spoiew Soci. ittiolo 0)1 Piteli and tar Authrnoone oil I.ubi'icftting oils Creosoto Benzolo Tur fumea fi -Nu p h th y am in o Skin Lutii; ftktn im ng Skin Skin Skm iSkin Bono rrmnuw Lnrur BUucUr R,ihl>i Mouse Mouse Mouse M Olisi MVmxo Mouse Mouse Mouse Dog M onlcey R abbit, gone, jnocso Conflicting oviilonr.o. sufficiently the past, history of their strain, so as to be able to allow for all the natural ills to which they are prone- Because, of (he long tunc required for the tests, extrapolation of tho results nuwt be very tempting when tho quantitative factor is found inmiUndent. Thai might happen us a result id starting out with insullioioni, living .subjects or because of .sum**, experioimtid disaster.. But any extrapolation, or filling up of gaps for th a t m atter, can obviously be very dangerous. It is for those reasons th a t biological tests must be conducted on n vast scale and with meticulous care in respect of such conditions as can he controlled. Tin (Jarcikorbxk; II vdrooakbons. Tho recognition th at extract.s from soot and from cancel--prod icing tars wore themselves carcinogenic stimulated interest in tho scandi for ingle olieraeids capable of producing m alignant tumours, In tho search the pioneering work of -Sir Ernest Kennnway on carcinogenic artificially produced tars wins important by directing attention towards tho complex aromatic hydrocarbons, nnd encouraging the search for the individual causes of coal-tar cancer. Eventually, in I11B2, Cook and hi co-workers tracked down in conk tar pitch a strongly carcinogenic hydrocarbon, 1! : 4benzpyrene (Pig. t), j/rem 2 tons of pitch they wore alilo to separate 7 g of tho materia!. 3 ; t-Benzpyrrme, t i n . 1. I : 2- Renxanthruceno. The " tracking down " of this hydrocarbon was done by a method which has more than academic interest. I t may readily bo brought to the w 2-1(1 -wi,n j-:sv!U!)\MKsr\:. <H\crH w o ricvivn u rn attention of nil wen and questions asked about it. It is fltiorciuxncf. It o'slremo ami testosterone (Fig had been observed by M aym w d and Hicger, who collaborated with ('ook, ronipoitoidii n; fhe human bn.- > IM th at the carcinogenic taws were all strongly fluorescent and possessed fluorescence spectrum bauds </! similar position ami distribution. Jloru II was a possible quick clue, without having to wait for the. results of biologh ul V' x 11,0 i I tests each of which involves many months or years to complete. Con- centration of the extra els using litis means of control eventually resulted from a variety cf methods, including the chromatographic, in the separation of the 3 : 4-hen/,pyrene described. 'This lias a closely related structure to 1 : fl-beirzanthnieent (Fig. 1) which, though itself inactive, has a similar typo of fluorescence spectrum, partly in the visible. This synthetic roaAwial is the parent hydrocarbon from which nearly all tho highly active carcinogenic compounds of this kind arc derived. I t is dear, then, that although fluorescence accompanies tiro general structure of the hydrocarbons belonging to this important; carcinogenic grouping there is no relationship between fluorescence and carcinogenicity. First, there nre m any known carcinogens which are not fluorescent a t all. i Secondly, although tho active hydrocarbons of this kind are largely fluorescent, the reverse is not tho ease- -as is soon from 1 : 2-bonzanthraeono itself. Thirdly, it is not fluorescence in general which is characteristic, cither visible or under ultra-violet light, but tho analysis of the spectrum and its classification. Those aro points to be home in mind, since as a result of Hiegor's im portant work ill-advised generalizations have sometimes been ma.de and suggestions offered, in respect of oils and other materials, to use fluoresceco as a classification of carcinogenicity and ns a guide towards tho use of particular materials. Of tho many hundred derivatives of 1 : 2 -bonzanthnwseno which have been prepared, many nre inactive, others only slowly active, and others again very powerful. I t depends largely on tho position of substitution and the nature of the snhstitulm g groups. Generally, tho higher tho ! substif tiling homologne- tho lower the carcinogenic activity. Small differences in structure may have very big effects on carcinogenicity. '('ho first compound of this class found to be cancer producing was 1 ; 2,5 : fi-dihoiizanlhrocene (Fig. 2), nZ 'X//X;:v' Oiolvslmol t'v, Other polycyclic hydrocarbons of tin- ,. have also been synthesized and snown realized th a t these are also myimm-l mad in structure from the benzpyrenes and , Tho skin tumours produced by H esn compounds are truly malignant, and I; spontaneous and human cancers. T hat is the real answer to (he u-ry n significance of this synthetic woik ' Then lit multiplying tl e number or hydrocarbon of inducing Miser ju experimental aninn 1 results are consistent, and repeaU.bli me, in the study of the form of uraip, tier i cancer, as well as in thiovdng light on t; > of cancer in the huirmu body. Whether .-1. intermediates in spontaneous human >,,i relationship betas oeu them and hotly m ai i , a a m atter for speculation. H ut it is ole. must be opened wide---and everything wu scrutiny. There me, then., two great reasons ha relationship to the earner problem Th believed will be a relatively short-lei m 5 : tho oil industry and there is the possibi thoroughly organized research and study u It. ma,y bo reiterated that site!' n mu,ill : /\ A can be, traced to actual cause th a t it is <( duos should bo followed up inexorably I ra V K /\z rry V /v \A / i 1 i 1 rr L. J \/ 9 : 10-Dimethyl-1 2- 1 ; 2,5 : G-Dibenzant-nrueisne. bouzanthracone. Cliolantlirono, i Krn. '2. i I One of tho most powerful is 9 : 10 -<iimethyl-l : 2 -benzanlhraoeno (Tig 2 ). I Others may contain nitrogen, sulphur, five-ring groupings, or incompletely 1 closed rings. Cltokittlirene (Fig, 2) is of interest as being a powerfully industries, petroleum is of small import,m. must, be repeated that this relatively flip importance because' of the highly orgaiu/. varying chemical nature of the crude oil,-, the widespread use of petroleum prodm-H " The oil industry has been eonewned n, the following ways . --- (a) Occupational. (!) Amongst paraffin-wax wor,m,,, , (2) Amongst, lubri; nting-ml u.vu ,i-. active carcinogen related to cholesterol (Pig. 3), and tho sex-hormones (3) In the use of rutting oils. U, r W C K K AN 11 rKTKiiMir'i'l \n ,i) FNyiTinxvn'iv rv , fA-sonn \ m > .rviiPT.id'ivi *11 h naked about h , It is Jluoraicmce il. aistrono and testosterone (Tg. b), all of which aie, of course, normal and Hioger, who collaborated -with (look, components of the human body. all strongly fluorescent, and possessed mtuhir position and distribution. 11 ore having to wait for the results of biological yi mv mouths or years to complete. (J011- this means of control eventually resulted Y ng the chromatographic, in the separation jf 1 This has a. closely related structure IliiG / H,, / \ Y X / ( 'SioIgbictoI ll,' ,o ll.,' ,011 V /> '\ / \ r i. t HO-"' ' Y - ' Y / O^'Un mo 1L>9 i ()X \ x \ x hieh, though itself reactive,, has a similar Kiu. ii. i parity in the visible, This synthetic, u from which nearly all the highly active ind are derived, ;h fluorescence accompanies the general elongmg to this important carcinogenic between fluorescence and carcinogenicity, dnogeus which are not fluorescent a t all. hydrocarbons of this kind are largely use,--as is seen from 1 : 2 -beuzan thru cone eence in general which is characteristic, t light, hut the analysis of the spectrum 1 Other poly* vclic hydrocarbons* of tho phenanlhrene and chryYono sorioa have also been synthesized and shown to bo carcinogenic, but f will 1; realized th a t these are also asymmetrical ring compounds, not dissimilar in structure from the benzpyrenes and benzanthracenes. The akin tumours produced by these synthesized or nature 1 chemical compounds are truly malignant, and indistinguishable in natiu-e from spontaneous and human cancers, That, is the real answer to tho very natural question of wi.nt is the significance of this synthetic work 1 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 u mind, since as a result of JHiegor's imxat.ions have sometimes been made and ils and other materials, to two fluorescence city and as a guide towards th e use of results ate consistent and repeatable may have the greatest importance in the study of tho form of occupational and generally environmental cancor, as wol1 as in throwing light on tho course and ultimately tho cause of cancer in the human body. W hether such substances am concerned as intermediate hi spontaneous human cancor, or whether theie is any tves of 1 : if-bomanthraccnio which have 0, others only slowly active, and others s largely on the posit,ion of substitution t.iug groups. Generally, the higher the Aver the carcinogenic activity. Bjhh.11 very big effects on careblogonH.ity. lass found to bo cancer producing was 2) relationship between them and body materials of apparently allied structure is a m atter for speculation, B ut if is obvious th at here is a door which must be opened wide and everything within subjected to the most careful scrutiny. There me, then, two great, reasons for ihe study ol petroleum in its relationship to the cancer problem. There is the attack on what it is believed will bn a relatively shint-term problem--occupational cancer in tho oil industry; and there is the possible application of tho -csulls of thoroughly organized research anil study to the cancor problem h> a whole. Y\ " > T ') YY Y J A/ OH, Xx i Y \/\v \ v j1 f` j1 :; yvv I t may be reiterated th at such a small proportion of all human cancer 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 ui,,uy other industries, petroleum is of small importanco in cancer causation, But il must be repented that this relatively slight connexion may be of great importance bora use of the highly organized industry involved, ll e greatly M)irnftthyl*l : 2iiy,snf;in`n.o<vno. Choli-mt-hrmiH. varying chemical nature of the crude oils and the processes concerned, and the widespread use of petroleum products throughout the world. Fin. 2. The oil industry has been concerned hi the aetiology of skin cancer m the following ways :-- 1 0 -diinet,liy!-l : 2 -bonzar.thracone (Tig. 2). plr.ir, five-ring groupings, or incompletely . 2 ; is of interest as being a, powerfully olcsterol (Tig. 3), and the sex-hormones (a) Oecu-palimiai. (1) Amongst paraffin-wax workers, iu shale, (2) Amongst luuricating-oil users as mule-spiinjors' rancor, (3) In the use of cutting oils. 42 wa.u : lINVlltONSiliXTAI, OANOlill AND I'ljTROIiBOM. (b) Muiperimbntid. (1) As sploctivo-solvouti extracts. (2 ) In cracked oils of low volatility. If is not proposed to consider these*- subjects mruUlm or chronologically. I t will bo 11101*0 to tlui point to look (it those regarding which there has been must diwnissiow. Many of tho m atters of broader interest will then arise in passing. But. first, it must bo pointed out that both upidomiologiealiy and experimentally those portions of petroleum concerned are within the high?' boiling ranges. Ho far there is no suggestion th at cmeinogenioity is directly concerned with (lie volatile Imv-boiling or intermediate products such ns gasoline, kovosme, and gas oil, Nevertheless, th at does not exclude the hydrocarbons which may be present in such fractions. Benzene itself, under certain conditions, is not free from suspicion, despite the fact th at it is a chosen solvent of the biologists for the application of carcinogens to experimental living subjects. At present potential petroleum carcinogons appear to be concerned chiefly with those fractions generally known as : (a) tho wax distillate, and (b) the lubrieating-oi! residuunix. Those, in effect, cover tho whole lubriciiting-oi! rung, with tv boiling point- from say 2 0 0 " C upwards. Tho range would include the lowest-viscosity spindle oils up to those practically mm-vohiUlizablc a t ordinary pressures, like tho heavy machine oils. tv is also to he noted th a t tho Hat includes on tho one side* shale oil and cracked fractions which have been subjected to high temperatures for their fundamentally reeonslruetivo production, and on the other side lubnenting-oil distillates mid residues which, by premise have not icon chemically changed during fractionation, or the slight changes in which have burn negated in tho normal course of refining. Th distillation range in both classes would, of course, cover the possible icurronce of those carcinogenic hydrocarbons--naturally known, syathosizwl, or yet to coma which have been referred to. Paraffin Wax axpSham*; On,. "S| The light oils and wax derived from .shale oil have bug been recognized 1t a. causes of skin cancer. Bell in Edinburgh reported scrotal cancer of a | : link: worker in 187<>, and Volkniaitn is quoted by Le.itch as recognising " i skin cancer as a result of shale and lignite occupation in Germany one year J earlier. I Dermatitis is known to occur amongHt the shab-paraliin workers, but | there is no record of petroleum operators with pantlm wax having been ft subject either to derm atitis orcancerous growths. #* f t is most likely, even in shale, th a t the irritant or active constituents ' are not part of the wax, which is paraffinic by nature as well as by name, / but rather of the oily coloured components accompanying tho slack wax. ' Thesn are known to bo chomieaUy roaetive, and are not necessarily allied in nature to tho orystallino paraffin wax. Indeed, Berunblum has ex tracted from 'Blue Blink* Oil the wwue 3 : -I-benzpyrene as (look identified I in conl-tnr pitch, K iM l'AL OAN 'Clm AKJ> PI'W OLTjrrW , .tracts. volatility. these subjects mriatlm or chronologically, )i: at those regarding which there has been rnttius of broader interest will then arise pointed out that both epkkstuologically is of petroleum concerned are within the uH'e is no suggestion th at carcinogenicity labile low-boiling or intermediate products i oil Nevertheless, th a t does not exclude present in such fractious. Benzene itself, free from suspicion, despite tho fact th a t Jogisls for tho application of carcinogens un carcinogens appear to be concerned rally known as : () the wax distillates, nans These, in effect, cover the whole mg point from say 300 (J upwards, Tho seosily spindle oils up to those practically satires, like tho heavy machine oik. 3 list includes on the one side shale oil vo been subjected to high tem peratures tetive production, and on the other side tiducs which by promise have not boon ionation, or tho slight changes in which course of refining. ,h classes would, of course, cover the inogenio hydrocarbons naturally known, i have boon referred to. ax A.vi) Shale Oil . `i from shale oil havo long beau recognized I i fidinburgh reported scrotal incur of a | nann is quoted by Leiteh ns recognizing i d lignite occupation in Germany one year amongst tho shale-paraffin workers, but operators with parafin wax having been icoi'oiiii growths. }, that, tho irritant or active constituents i paraffinic by nature as well as by name, ornpoimnts accompanying the slack wax, :y reactive, and are not necessarily allied affin wax. indeed, Bcrunblum has ex- snmt 3 ; 4-benzpyrene ns Cook identified i wrr.D K ' N V f K n X ' I C V t A L C A N C E R A N D r E I K O I . E D M >1 UI,B-;-ST*[N NERA' ( ANOBil. Tiie occupational disease! oi' mule-spinners' rancor has atfcraui.od much attention in the U.K, It. is indeed around inuio-spinncrs' cancer that meek of tho interest and concern in petroleum carcinogenicity ha- revolved. Its history is already a trifle obscure, but .it appears to be the ease that fcloutham and Wilson in 1022 drove attention to the high ineidoneo of scrotal eaneor in Lancashire nmln-spinners, and th a t irt 1924 Loitoh was able1 to produce tumours in mice by applying solutions of the lubricating oils involved. Mulo-spinnors' cancer is a skin cancer, opidomiologioolly associated with fcho occupation of cotton-spinning with fcho mule (Fig. 4). Operators who succumb, generally do so after a long period of working ututor tho conditions prevailing - -Homotinio over twenty years. The disease may attack various parte of tho body, but; like soot cancer und paraffin cancer is frequently associated with tho scrotum. The conditions of operation wo of importance, and have been recorded by Dr E. M. 11rock bank,4 who says :-- " Tho spinner works baro-footed in vest ami overall trousers without any shorts between them and the skin. As the illustration shows, he leans over tho mule to join or piece with the thumb and finger tho brokon ends of a thread of yam . . . Tho scrotum constantly comes in contact with oil on the trousers. The vast majority of men piece with tlu> left hand, and for this reason the left side of the scrotum is affected a similar number of times. . . ." The temperatures in the mule-spinning rooms are excessive, and may exceed 105 F. Brockbank also quotes Horne Offioo records (Table ] V) giving informa tion on the incidence of tho disease over some selected years. T a b i.t: XV. iSpiiiriera an d pincers, Cases p e r 1000. 102 48,029 1-83 1930 40,714 1-75 193 32,232 1 27 1!)40 23,00!) i -78 ! 94(1 17,671 2-0P T otal CttSOS. 88 82 41 41 36 T o tal (loatiis 20 21 12 10 21 Ho points out that the inorea.se in number of cases per 1000 in recent years is due to tho greater proportion of older spinners a t work, and the greater liability of cancer of any form to occur. Manchester CoMMm'&ic on Cancer. As a result of the observations of Southam and Wilson and tho work of Leitch, tho Manchester Corporation somo years later, in 192S, set, up a large committee further to investigate cancer in general, and mulespinners' cancer in particular. Experim ental work was placed undor tho direction of Dr G. C. Tworl and tho cancer research committee under the ;'M-i u \ v n v v - u e \ i u c A w . e r i s h e h 'ip o i t:t w c.biiirnmnship of J)r M. W. Broeklnmk Report worn published anmnilly, and accounts of the researches published in the medical Press. These confirmed tin: observations of Lniteh, and supported his conclusions that, mule-spinners' canecr is caused by carcinogens present in the lubricating oil used. This work was substantially subsidized by tin? oil industry notably by the Shell G roup, the Anglo-American Oil (lom ptniy, and the AngloP ersian Oil Company In }93`i the Manrhesfor OoHimiUec proposed a .standard for mineral oils to enable the textile Industry to choose lubricants which should bo substantially free from carcinogenic properties. The criterion was believer! to condor tests or mice obsolescent, and misted of a, believed relationship between irrmogeuieity and the refractive index and specific gravity of the lubricating o:l. The qualification read :-- Mule-spindle minonil lubricating oils should have a. specific refraeuvity behnv 0-5530 when (he speeiiie gravity is above 0895, or a specific refm ctivily be.ow 05509 when the specific gravity is below 0-895. By specific rcfrarivit.y is meant when n is the refractive index for d-line sodium light, and where d is doiwifcy in grammes per millilitre at 30'-' C," s : n> its - hi view oi the impoitiiiicc ->i i)u OonimiUoe's c.om-lniiiont w in nnlm-ii, Data showed this sncificai ino -< 1 in blonds of paraffinic (Oklahoma ( u ! oils, curves, and checks m w\-> ;-u.N h , \ hori/ontal) and speeiiiu grm ity i o-n. 1 that, blends IjaHveon 45 and 71 pec cm 71 per cent in the other are dangeimm - stocks would be sire. Many otin-i sun complete lock of acoopUibibn of r e made clear that `'ex ten t of lehnemem to line up with " degree of caruinom i i u . tiio specific refiantivity/density rehn on-1 By tins time, however, it wa- <>w, Mivnchoster Foininkt for " iifm-cniM-im >n 4 wrongly been widely accepted its t! < . This was nnfort mate foi several reii-mn-- {a) The textile workers, the ui extent the medical profession weir ' of the case, and possibly lulled inn. of oils such ns those described ver- 1 praetico. (b) The oil industry found Ihe d able, and many oi! scientisrs fell, hi i (laid in the textile nuhiMry hi conditions medical inspeeUon, <h. susceptible t-o skin troubk-, and so o These things wore known, from ifm a> s f with shale oil and occupational od derm i indeed, paraffin dermatitis and p -ral'lu. i Luo shah' industry its being under too. older men whe had contracted tiiwm yea in the U.K. and in the U.X A. m tieby systematic washing and other ream i t.uc application prior to working of o wore very encouraging. Another point which seemed u> siipp< problem was that enquiries in of bet Fiance, and fi dia failed fo disclose He in their textile trades when wotkhg, u i' and with similar oils to those m ham m (c) I t meant tin'll insulliat-et u development--or rather tho fontm.- I oils. If had been apparent I. mm ment -possibly by .solveni .-ehm l i agents as might lie expected !> I 1 logical approach to tlie prol lem concerned, I I i'\ N f Kli A> 0 I' i'/ntOl.Ul'M. lie Reports were published annually, idi-siied in the medical Press. These it, and supported bin conclusions th at cavemogens present in I,lie lubricating isidized by the oil industry- notably icrioan Oil Company, and the Auglo- ,tee pioposed a standard for mineral to choose lubricants which should be : ghavi'y ai w i/Wi "S95 _ ur. > j 1CEMT SIOCK 67! n 5. ;nie pioperlies. The criterion was isoleseent, and consisted of a believed ' and the refractive index and specific, specification read : 'eating oils should have a specific i the specific gravity is above 0'895, i 0 5500 when the specific gravity is >i, - 1 hiv'iiv is meant ' -r , where n is tin d uni fight, and whore d is density ir m r s '51 ' s T M |\ " 1 l T 'r r c ' 1 ' V M ' i.~ In view of the importance of the subject, the validity oi the Manchester Coinn. tleo's conclusions were, naturally closely examined. i Data showed this specification to be unsound. For example {Fig. 5; in blends of paraffinic (Oklahoma City) and naphthenic (ifutf Coastal), oils, curves, and chock-curves cross the specif,cation limits of refraelivity ( horizontal) and specific gravity (vertical) ui such a. way us to indicate that, blonds between -15 and 71 our rent in one case and between 20 and i 71 per cent in the other are dangerous, whereas all other blonds of the same stocks would bo safe. Many other similarly collated data also indicated I complete lack of acceptability of the specification. In addition, ir, was i made clear th a t " extent of refinement " the characteristic most likely to line up with " degree of carcinogenicity ' goes in tin* opposite diiection to the specific refractivity/density relationship when applied to paraffinic oils/' By this time, however, It was over late. The too-mueh p iblieked 1 Manchostei Formula for `` non-cancorona oils " had undorstandinglv, but wrongly been widely accepted as the complete solution to the 'problem. This was unfortunate for several reasons : -- (n) The textile workers, the employers, and to an appreciable extent the medical profession were being misled as regards the facts . of the ease, and possibly' lulled into a false sense of security'. Blends of oils such as those described were by no means unlikely to exist- in practice. (I>) The oil industry found the Manchester specification unaccept able, and many oil scientists felt th a t insufficient attention was being paid in the textile industry to p m w n tia n by cleanliness, working conditions, medical inspection, change of oce.upat.ion for workers I susceptible to skin trouble, and so on. 1 These things wore known, from the petroleum industry's own experience, with shale oil and occupational oil donna.tit.is, to bo of the first mmortance. f Indeed, paraffin derm atitis and paraffin concur wore already iegarded in i the .shah, industry ns being under control and largely confined to the l older men who had contracted them years previously. Also, results both in the U.K. and in the (7.S.A, in the control of cutting-oil dermatitis, by systematic washing and other regularized forms of cleanliness and in the application prior to working of protective creams and ointments, were very encouraging. Another point which seemed to suppoit this form of approach to the problem was that enquiries in other countries--including the U.S.A, i Franco, and India failed to disclose the oeetirreueo of occupational cancer in their textile trades when working under apparently similar conditions i and with similar oils to those; in Lancashire. * 1i (c,) I t meant th a t insufficient attention was being paid to the development--or rather the tasting and use, of truly' ijon-ciu'cinogoiiic ods. I t had been apparent- to many oil men that, more drastic refine ( ment- -possibly by solvent extraction, or by treat moat with such agents as might, be expected to destroy the carcinogens, was the most logical approach to the problem as far as the lubricating oil was concerned. "IHi ' v r r . i i f r . ' V i a O ' n i F v i vi i >,m i?-i a n o KTt' n i n s r r (d) It. delayed consideration of systematic examination of petroleum for the purposo of separating the act'.ml enmnogmw a<l study of their chemical structure and properties. 5 Wauti mis Con u m o s s . In 1D-13-44 arose two matters of some sigmlieuums in placing the study of the carcinogenicity of petroleum on tho right lints. The first was tho bringing (o notice by Twort of the possible caremogon.'e, or afchwiWso f noxious effect of iubricating-oil extracts, which midor war conditions were in tiro as substitutes for extenders, plasticizers, and binding materials which could no longer bo obtained. The second was ail approach to tho Petroleum Board by tho federation f of Master Cotton Spinners' Associations and the Amalgamated Association of Operative Cotton Spinners and Twiners, asking th a t oils to tho Manchester Specification ho m ade available to the textile industry, tn making this request thoy quoted tho Manchester Committee, as stating . . testing of oils from cotton mills for cin'omogenicity luxe boon practically discon tinued, as all mineral oil being generally used pooled and is a mixtures of oils. , . This, of course, was not at all the way in which tho Lubricating Oil Pool actually operated ! But it gave tho Petroleum Board the opportunity of summing up the situation, and pointing out th a t oils to the Manchester specification had not been asked for riming the previous four years of war cither by distributors or users; th at such oils could undoubtedly have boon supplied if wanted, and the Board was prepared at once to sot aside oils meeting the specification in two ranges of viscosity-- despite the fact th a t the efficacy of the specification was questioned. At the same tim e tho Ministry of Fuel and Power drew attention onco more to the need for tho improvement of operating conditions in tho cotton mills. Those two m atters obviously tied up together. If, by solvent refining ! oil stocks from which lubricating oils arc marie, the extracts were more carcinogenic than the original stocks, then the refined oils iniiel bo leas no. `This conformed with tho oil industry's past, views, and tile Petroleum Board arranged to finance biological testing nil rcscarclx on tho m atter I at Birmingham University, Work was initiated by Prof Harwell Wilson and Dr J). L. Woodhouse in the Cancer Research Laboratory in the D epart ment of Pathology and under the egia of tho British Empire Cancer <Jampaigm Committee, After about twelve months' investigation and testing of petroleum extracts, interesting results were obtained to which separate reference ; will bo made. Wh ite Oiks. Throughout the extended study of the relationship of lubricating oil to nmle-spinnura' oauucr the question of extent, of oil refining has cropped up frequently. As far as the oil is concerned this has always been the f i chosen aspect to tho problem of the chemist ami oil technologist. From 1 i quite early days Tworfc expressed belief in white or mo<denial oils being the least carcinogenic of all lie tested, sharing immunity in tlnri respect with fatty oils. The possibilities of removing reactive carcinogens from l mineral oil by earth treatm ent, oxidation with air or chemical, solvent u r r . D 1 i i \ v r u . - \ , ' w , extraction, a fid troni men1, .u ,, ,,, T hat possibly was lue i,o n,amount and expense of the vvuik n>, perhaps in those, most iri.iiti.\:,-h , In the early days of liMti, lu.w> i r Oil Refinery Group, in coup h-h.ii, u the uso of technical or medici.ml unit These oils are selected petroleum , U.1 acid or oleum. The proposal v/iw brought u> q,, whose advisers were qnirkiy aim q, , mended that, if a p r im fin . 0 .,. ,,,, gomeity of such white oils, limy -1.>, textile trade as spindle oils. Kvh, , available wax meagre. Lever-tin e-.-, of Labour ami attended by repiv-eu! trade, and tho petroloum iufin.sii'y, 1 and Power to make white oils av ail, firmed, despite tiro scarcity mid del Simultaneously, tho Petroleum Bum subsidy of research work on the very limited information on whuh W ith tho exception of u few more hi onco again nothing happened fi-r m years. There wore practically ho domanda for supplies cither fro n o, In 1.SM8, however, the Master Spun . called into being the ad wr rommitt,- sonlation front the Shirley Instiuiri-, corroboration by Wnodhouso of Bun, of white oil samples sulunil.fori by rim Decisions were tltoruou marie le Hpinncrs' Associations to .ri andar. 'u< practical tests showing th e n lo have -, Such mill trials, curried out v, ilh p > with fatty oil, ali of comparable \ i.,ofrand unexpectedly very little ciii'mv power consumption. The ad kvo commi! ire concorra'! 1 h 1 being brought under the eonr-ol . Ministry of Labour and National S m - W h it e O il D ': I t was remitted to lie petrel.-iii. a specification to cover aiutai.D ui.c This Ima now been dime, and th n o Committee, by whom it may be re p dato. The specificatimi is bared prim.u 1. r v N 'r ii xs'ii m r a o i b o w . 1111.0 ! R N V R O N M I V T W r Y I U i \ ' [ l t ' K'l H O I M ' \ . o.r.' fsystematic examination of petroleum extraction, acid treatm ent, were all discussed, but, nothing was done. the actual carcinogens and study of T hat possibly was dun to the limited testing facilities available, Mm opert'.es. f am ount and expense of the work involved, and lack of a sense of realism perhaps in those most intimately concerned. ('ON DTTIONS, In the curly days of 11140, however, the step war. taken by the .Manchester Oil Refinery ("roup, in conjunction with Twort, of definitely recommending some significance in placing the study the use ol`technical or medicinal white oils as spindle oils for mule spinning. on the right' linea. 'The first was the A. These oils are selected petroleum distil la te heavily treated with sulphuric o possible carcinogenic, or otherwise acid or oleum. acts, which under war conditions were The proposal was brought to tin* attention of the Petroleum Board, q plasticizers, and binding materials whose advisers were quickly a live to the logic of the suggestion, and recom 1I io Petroleum Board by the federation ons and the Amalgamated Association iners, asking th a t oils to the Manchester the textile industry. In making this Commiltoo as stating . . testing of gonicity has (icon practically riisconirally used is pooled and is a, m ixture is not at all the way in which the ed ! Tint it gave the Petroleum Board situation, and pointing out th at oils not boon asked for during the previous mtors or users; th a t such oils could wanted, and the Board was prepared x-eification in two ranges of viscosity-- the specification was questioned. A t and Powor drew attention onoo more perating conditions in the cotton mills, up together. If, by solvent refining its are made, the extracts were more cs, then the refined oils m ust be less Instry's past views, and the Petroleum d testing mid research on the m atter was initiated by Prof. Haawoll Wilson er Research Laboratory in the Depart* gis of the British Empire Cancer mended that, if a prima facie case could be made out for the nou-cu.riuin>geniuity of such white, oils, they should at once be made available to the textile trade as spindle, oils. Examination disclosed that, the evidence available was meagre. Nevertheless, a t a mooting called by the Ministry of Labour and attended by representatives of other ministries, t,he textile trade, and the potrolonm industry, the decision of the Ministry of Enel and Powor to make white oils available as textile lubricants was con firmed, despite the scarcity and dollar cost of such oils at that time. Simultaneously, the Botroloum Board announced its further financial subsidy of research work on the subjoot at Birmingham to supplement the very limited information on which the derision had been made. W ith the exception of a few more letters and articles in the trade journals, onco 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 cons timers or distributors. In MM8, however, fcho Master Spinners and the Cotton Operatives again oa Ifed iitto being the ad hoc Committee of 1946, with the addition of repre sentation from the Shirley Institute. By this time there was fortunately corroboration by VVoodhouse of Birmingham of the biological inactivity of white oil .samples submitted by the Petroleum Board, Decisions wen thereon made by tho Federation of Master Cotton pinners' Associations to standardize oil the* use of white oils subject to practical tests showing them to have miti/thle hdirfeating value. Such mill trials, carried out with plain white oils and white oils blended with fatty oil, all of comparable viscosity, showed satisfaotory performance and unexpectedly very little dilTemtee amongst themselves us regards 'estimation and testing of petroloum ibtained to which separate reference power consumption. Tho ad hoc committee concerned has sin achieved an official basis by being brought under tho control of the Factory Department of the u Oils. Ministry of Labour and National Service. of the relationship of lubricating oil n of extent, of oil refining has cropped i concerned this has always been the 5 chemist, and oil technologist. Prom eliof in white or medicinal oils being crl, sharing immunity in th a t respect f removing reactive carcinogens from dation with air or chemicals, solvent W h it e Oil .Spec ific a tio n . I t was remitted to tho petroleum industry roprosontativOB to submit a specification to com* suitable white oils for adoption by tho trade. This has now been dorse, anil the draft spcification is in tho hands of the. Committee, by whom it may be expected to bo published at an early date. Tho specification is based primarily on definition of nature and pro- A i i a > . k v >f H ' i s M H N T u , r - ' . x ( 'a-- a \ i > ' i r T i n i J c i r a . \| 1 o >:v\ a a , >ij. i ,, duoium, a ml upon colour It, is recommended the, colour hernia bo of from stock''im i'h-i',| iron, H , t, tile highest standard known, hr repiesotil-iug the most drastically refined oils, id ii<MM*i|uenlly those likely to in; tin* least, U'tuilopentmUy active troutmi'iii kw h foMi-mei't o . y selective solvt-nl,- Tlu~.e o-iu-.,., i , Ijitter, when further testing ansi wvc-atigulion has !h;ui) carried <mf, ring-type compounds, which urn1 . it may bo possible to relax the standard without danger. This joint action of the cotton and potrolcum hula-T-rios, with tin- support nnI under copuihto tone itm-ms, so ill u- hi - i oxidation for example, and i- mm. t standing of the fJovermnetit, is a line example- of co-operation for the common good. It makes up somewhat for t-ho period of mmundersUmdmg oil. Tlio mii-tcri.'ds tested n t Binmi.y mu and diversity of net-ton of Urn past. Expenditure of lime and money, mu! derived variously from : - ultim ate cost of the very special oil concerned, have been no obstacle in dealing w ith this sped of the fell disease, ! Vc.lIPZl'd (Colon, Luguiuil.i;,, C As far as can lie seen a t present nothing further can be done as regards V S A , (!utj CoaA i f t i h B m,> the oil. Colomtia, There may, however, be tmibrseen snag, and it is essential there should Kqiin'l'ir, be no false feeling of safety. It is most sincerely to lie hope! th a t liothuig will interfere with the campaign for cleanliness, for protection by means of i MiudU East (Persia!, U.K, (Eakring), clothing ami barrier creams, and for better conditions of operation. The roeominr.nduUtui of the Joint- Advisory Committee of the Cotton Industry Tho Kolvenl-oxtsv. '-.inn proees-t s . (1945) for him adoption of autom atic wiping-down motions and non-splash Seleelo), Ikleicumt (kiiiy.of'SO,), , mi I ( devices is good as far as it goes, but no layman can but wish th at mule Altogether, twelve pntiuk-inn xuw spinning, with its attendant conditions as described by Or Broekbank, over a Dirioi of some twelve maul I. could be exchanged for olhet methods of spinning less exacting, tests followed, Hlid gave lilluh. idei, - compared by cheek fe.-ts with lain \ C atty O il s, chemicals iu mildly used ,,i ph- te e ,. ( Statements to the effect appear from time to time in the technical and Irade Press th a t animal and vegetable (idly oils are non-canm ous. Tworl I has recorded all such oils tested by Him as being innocuous; hut, he has also pointed out th at oleic and lino laic acids (which may, of course, be present J to an appreciable extent in commercial fatty oils and to a small extent l oven in well-refined oils) are capable of producing non-mnlignani tumours iu mice. They are also capable of amplifying the cancer-promiemg elieeis of certain chemical compounds, f t has also been stated th a t when using sesame oil as a carrier for chemical carcinogens the blanks with sesame u-lyno were not free from activity,s These m atters are mentioned, as the specification for while oils retorted to may factually or tacitly permit compounding, In this it would be iu lino with the observnUims of the Manchester iJoinir.kfee, f t is well to m d i'/.e, however, th a t there is no full oleumm*. for fatty oils, and in view of the difficulty of defining their nature and their purity the author would industry. The result.--, varied -I'.eiut hat i- -i, I showed shat sohvrd- tviimup d-o.te- carcinogens iu the extracts. T`ti : , activity than i.om-xpondmg ir po- materials already m use, Ki-vi-rtlmlrw 1 should oc used with cirrmrispoi tii.i especially avoiding eonti.innl l>diK Recently some attention 1ms hi u dm extracts ns tone oils in foundries, fb- produets ices readily obtainable. 'fh, , such recent are of extracts and e : cancer amongst ibuudiy workers, T. possibility fo' ail deeompositiiui pi>1 tem perature being enremoacuie. suggest limitation of their use until further work 1ms boon done. All concerned would wish to ex/prt?; their appreciation to Ur C, 0. f Twort for his devotion to ids purpose, of eliminating mule-spinners' ameer. i The single- m indednm of Twort and his co-workers---and of the Manoheatev flommittee as a- whole -has been responsible, both directly and indirectly, for much of the progress made. t'rrn x o In a recent, pa,pet by Dr i'r a 'kale i drawn to the possible effects <>' exp--s engineering processes; and m .-tuuiuU C a r cin o g e n ic ity oi? Oir, E xtracts ( ma-tio um-ubmiitg LTaler these mi- i i folliculitis (m.hunuUou of the lutir hull I The work of Woodhouse at Birmingham on behalf of the Petroleum affected. Moreover, about one-thud a Board, to evaluate the carcinogenicity of oil extracts. covered materials of one of two kinds T'nesv v arl- ' U. cw .'l'.li I'K T I'O I.H K rcceininonded that colour should bo of epresontmg tho most driwticnJIy rolincd I/O be the least earuiuogoiiU'ally active, ml invoshgai ion hit been carried out, sUuuliuri without danger. This joint >ndn-.rne.-i, with the mippori oral underit line example of co-operation tor the w hai lb: the period of misunderstanding Expenditure of lime and money, and ml concerned, have )oe.ii no ob-daclo in disease. 1, nothing forth or can lie done a regards v.n snags, and it is essential there should most sincerely to be hoped Uml nothing >r eieanluiess. for protection by means of for better conditions of opera:ion. The isory Coimnittne of the (lotion .Industry tic wiping-down motions and rum-splash but no layman can but wish th at mule litmus as described by Dr Brock hank, hods of spinning less exacting i'T Y O n s . from tune to time in the tecfmieai and i.ble fatU oik are mni-eauee.rotix. Twort him as being irmoenouK ; but. he lias also acids (which may, of course, be present K'l'tna! fifty: oi|s and to a sinnl* extent .do of producing non-iimligiutnt tumours amplifying the cancer-producing effects . using suanto oil as a carrier for chemical o alone were uot free from activityr! the speeilieafkm for white oik referred - compounding. In tins it would ho in Mauri icstei (Jotninittce. Tt is well to 'nil clearance for fatty oils, and in view' almv mid their purity the author would il further work has boon done. xprn-s their appreciation to Dr 0. 0. iso of eliminating mule-spinners' cancer, d his eo-workets---and of the Manchester esponiublc, both directly and indirectly. v or On, Extracts. rr.nngha.rn on behalf of the. Petroleum deity of oil extracts, covered materials u l,i> : i; v \ i m i w i n v r u ( W ' r i c u a n i i r t . T H o i . K r . M , >i n from slocks derived from different crudes by various processes of solvent troal merit. Such trontniont is a process of physical extract ion with selective solvents. These remove Hi' inure aromatic nod naplit-lioittcring-type compounds, which include many of the more eliwiiieally tit eepfible eonstitueiUs, so l hat the rulVutate is mneli more iw slitn t, to o xulaiiott for (ample, and is more paraffinic in nature than tho original oil. '['lie materials tested at Biaidugiuun wore all products from feed-,stocks derived variously from , - Ve.ne.6uHa Colon, Lgiii:illi,d, Concepcion, and Tin Juana), c U,U.A. Oulf Coast (West Beaumont,), Colombia, Eqmular, Middle East (Persia), U.K. (Ifiakring). Thu solvent-extnuil,km proves:;-! ecmuonied included Duosol (propane/ Seine to), Kdeleiuut (benzol/SO,,), iuhI furfural. Altogether, twelve petroleum exfcrii.ers of different. kinds wain.; tested over a period of some twalva month.!. A second scries of eoiilirmatory tost followed, and gave almost, identical results. The first series wore compared by check-tests with known carcinogens and with certain okorr.icak normally used as plasticizers and extenders in the rubber industry. Tho results varied quantitatively from one material to another, but showed th a t solvent refining tended, where they existed, to concentrate carcinogens in the extracts. The most active wore lower in biologica activity than corresponding codl-tai products and less noxious than certain materials already in use. Nevertheless, it was apparent th at such products I should, be used with oiriyiinspeetiim and under coutmllcd -onditions, 1 especially avoiding continual bodily contact Recently some attention low been directed towards the use of pelioleum extracts as core oils rt foundries, taking tho place of linseed and other products less readily obtainable. There can be little connexion between mioh recent use of extracts and a believed above-normal nr.iuenoe of cancer amongst foundry workers, but it draws fresh attention to the possibility of all decomposition products of organic m atin at high tem perature being carcinogenic. (JlfiTlNO Oil s . i In a recent paper bv Dr Cruicksliank and Prof. Squire *' attention is drawn to the possible effect of exposure to mineral oils of workers in engineering processes, and particularly to the use of cutting oils in auto ( m atic machining. Under these conditions woikerH are susceptible to oil folliculitis (mflninatioii of tho hair follicles), and the groat, majority become i affected. Moreover, about- oite-tlnrd of those examined contracted warts of one of two kinds. These w.vts are of ,i, type known amongst, tar- I W '' `m U (<f> !WV{KOSVF,'n\\1> CAx p w iNI* MSTfcOT IM'M. workers and rmdc-sphmoi's. There wore, m addition come oases of pro- i cancerous skin condition and one of scrotal cancer. 'riie.se observations may have- to be regarded us warning signs, and f certainly call for study and amclioi*atiou where, possible of the conditions j of operation. Ll scorns to be tliu ease that 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 hue spray which deposits on j the surroundings, including the operators, as a thin (ilm, The initial in flammation is mostly on the hands and forearms, but clothing becomes | charged with oil, and the general conditions in this respect are not dig- ] similar from those met. in mule-spinning. j The conclusion to be 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 ij undoubtedly caused try 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. I In this connexion Oruirkshank and Squire urge stricter methods of j prophylaxis--reduction of actual skin contamination by oil, improved J anti-splash devices, and use of more suitable clothing; higher standards 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 roams a previous paper by Cruiokshank 7 on the subject of their evaluation may oe rncom- f mended. As protective, the soapy type of oil-resistant barriers seem ' to be of limited effect, and rave the disadvantage th a t when after a limited 1 time they are penetrated by the mineral oil they give no aid to subsequent ( removal. Greasy protective, on the other hand, rapidly mix with the y contaminating oil, lint do assist subsequent cleansing. | In view of the dubious nature of some of the protective components, if is clear th a t a great deal more work is required on the subject. I O ro r ni/ atilvJe of PHfukum Ht {:> , The work sponsored ,o. Hti ome C ,, started by biological ir-um- m nhn account, o f this work is .............. I , If, had been determined In P c o th at work on he catcinoycnicii >. <>i , m ental basis as soon as pos.-cI i,- j the neeeHKary funds, ami an.timou,. Cnivermty to undertake the biokr... , Those, ftrrnngfmn-nts wore veil nudt i dissolved. Amongst its las! .ic m n li the Ministry of Fuel and Po\y.-i, appi accept responsibility for <,ouUm:.iti..i, sum to initiate the re-search, ft a, when needed, would he f,rtio mimy i The, Institute aeropled the n-sp u . formation (under its Research Cutum., which the author has the hntumi in o The Grom consider that work , , applied or ad hoc, nature, hut. r.n t mu active components present m pi-tro!< As there are hundreds of d'ff.ur m , crude petroleums, it is noe.-jisarv i choice. This choice is govene'd b\ (a) Diiforor.co of type and clist (b) Importance in extent of pi(c) Content of lubriuiting-in1 already indicated, had o, cm red i. (d) Supplies being tiio eonplcn (} Authenticity and rep.-cuuh Cracked-oil Products. C Medical Research UoimeiL Modern refinery practice is largely ooneomed with the reconstitution of petroleum hydrocarbons by moans of heat and catalysts. Under the conditions of cracking and reforming, most of the now products a,w mole- I cularly relatively simple. B ut thc-re is always a. small proportion of heavier i materials formed by re-condensation ancl polymerization. These, when j distillates, may range in boiling point up to this gas oils and light fuels. They arc preponderantly aromatic in character, and having boon aub- f jeoted to heat, treatm ent are not readily susceptible to heat. Their * molecular-weight range, for example M.W. 230-250, would include that of many of the hydrocarbon carcinogens previously mentioned, Jn view f of their nature and mode of origin it is not surprising th a t biological testing has shown some of these 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 be made j later. "l Quite seprrav.'ly, as a result of tin u gcnioifcy, the Medical Re-toatrh Conn, mitt,co with the terms of reft-renee " to initiate and carry old k mmineral oils and compounds of combined in use.'' The Medical Research Council, r CPrivy Council, and as such pus-mew,-- , upon such Ration. Tho Committee thus ionnt-d a, m in cancer pathology, the elen u-fi", and petroleum technology. Th > >. nom inated representatives to a- b no * Tin* M.R J Committee e-oik- elu ,ANC'l'f S M ' I'CTBftl.HI'M , -tire in addition dome rnscs of preirotal cunw*i\ be regarded as warning signs, and ;on where possible of the conditions e that whilst a little of the cutting the considt'nibio loss of oil known to it very fine spray which deposits on tors, as a thin film. The initial ini.nd forearms, but clothing becomes i d i t i o n s in tliis respect ft; not dis- >gil improperly dealt with continuous Phis is supported by certain epidemi cal. 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 11 coutaminntion by oil, improved suitable clothing; higher standards ive fcaniei creams; regular medical susceptibility id use of barrier creams a previous of their evaluation may be recomtype of oil-resistant barriers seem advantage that when after a limited il oil they give no aid to subsequent other hand, rapidly mix w ith tho [uent cleansing. ne of the protective, components, it required on tho subject. I 'ltODT'OTS. oucumed with tho reconstitution of f heat, and catalysts. Under the most of the new products are molealwuys d small proportion of heavier and polymerization. Those, when up to tlu: gas oils and light fuels, character, M id having been subawlily susceptible, to boat. Their VI.W. 230-250, would include th a t ns previously mentioned. In view lot, surprising th at biological testing josses* carcinogenic activity. This examined by the medical section to which reference will be made s " i . ' ) : i ' ' K v u ; u v M H s ' T A r . c u -u s k r ,\m < c r m i o i m i . ' i i i . 2i>l O r u a w iz a t iu k o r Rjssis aro , Institute of Petroleum, Itcaearct>Group Go, 2. The work sponsored at Birmingham University by the 1`clrulwwi Board started by biological testing of white oils and petroleum extracts. An account of this work is contained in a paper by Wood limn! and Irwin." I ft had been determined by the lAst-roksum Board' advisers, however, (/ th at work on the carcinogenicity of petroleum should lie p u t mi a funda mental basis ns soon as possible. Bor this purpose tho Board promised the necessary funds, and arrimgenienfs were made with Birmingham Univorsity to undertake the biological side of tho research work involved. Those ammgomcnts were well under way when the Petroleum Board was dissolved. Amongst its lust activities the Board, with the concurrence, of tho Ministry of P ud and Power, approached tho instituio of Petroleum to accept responsibility for continuation of tho work, and offered a substantial Sunt to initiate the research. I t was implicit th at further financial support, when needed, would ho forthcoming from the individual oil companies. Tho instituio accepted the resptmsibility, and implemented if by the 1 formation (under its Research Committee) of llcseiireh Group No, 2, over which th<' author lists the honour to preside. The Group consider th at work embarked on should not Ik: of an applied or ml hoc nature, but an endeavour lo separate nnd identify the. active, components present in petroleum and determine their properties. As there arc hundreds of different, oilfields and many hundred different crude petroleums, it, is necessary lo be realistic and make a limited choice. This choice is governed by :~ (a) Difference of typo and distribution. 1 (l>) Importance in extent of production. i (c) Content of lubrieafcing-oil fractions, sinec carcinogens, where i already indicated, had occurred in the heavier distillates. \ (d) Supplies being tho complete and untreated crudes. (c) Authenticity and repeatability of experimental supplies. i M edical'Re.se/trch Com,nit. Quit .separately, as a result of the attention paid to mineral-oil carcino 4! genicity, the Medical Research Council a t the ond of l`148 set up a Com inittao with tho terms of reference : - I " to initiate and carry out research into the carcinogenic action of mineral oils and compounds of other origin with which they may bo combined in use." The Medical 'Research Council, it should be explained, is a body of the Privy Council, and as such possesses all the powers necessary to embark upon such action. 1 The Committee thus formed is of high calibre, and includes specialists I in cancer pathology, tho chemistry of cancer, biological testing, statistics, and petroleum teehno'ogy. Tho various ministries concerned have also i nominated representatives to attend as may be required. Tho M.R.C. Committee works closely with I, Lb Research Group No. 2, I I.VNI nu ANI) l'irCKOnlOUM . tive. Tlu' ologramma embarked upon the iii-A instance to skin cancer, whilst. ! ns, I I'ceUid by Prof, Squires at .Birmingham, iwl, 1 reeled by Prof. Cook at Glasgow, ir. I search Group, No. 2. choice, of three entile oils is confirmed, i' their fractionation. The oils arc, il Co.) lixteimivoiy produced Middle , much used in the TJ.K ; of paiaffuiie- imig lubricating-oil fractions. g Lila (Shell Petroleum (Jo.). 'Typical wn history and producing well-known id-(ltLiiliminl {Soamy-Vacuum Oil. Co.). iontiuent distillate, bright stork, and H U) U W I I U , . U l i v i ' V I , C V S O K U V S ' O V K 'N O f . n VI. wit'll nil rasonio oil emu-sinir. are an indimi,lion of t,lie existence of amelioru- liv'i* properties in some form of petroleum, or even iu the petroleum eiitvhiopcns themseives. - Ilneper, W " lim'mmmeiiiil Piutcer," U.S, Uovi. P ri u i i n e Olisce, I1)!'? 2 P u t, Ita c v illl. l `hirmypea OUsei'Viiiioes." .17. i'u ttk, U*. ( `liemislry aie! Umilici-," Koviil liuti,mite >if Uhi.mi.>Uy (M)Klj. ' tinmlsmik, l. M, Mnfe-Hf>imiirs` <'imcur." lnKiiuiro, 1947, - Aulii. S. M. `' Spedile reiViit-tivity a m i ctuvtmvgenictkv of m uterai InbremwK oils," J. Inai, frinii. W i i . , SS, 84, 877. l il'ruifikKliimk, Ih N, ih , eie! Si|iere, II. t. ' Hlde iRiocer m (Sic -eerneeri;.:.; tmhtriry from th ime yf minerai oi." Jirii. ,1 . Imi, ,M,i,L, |sf), 7 , t -11. ('riiicksHtmk, U, N. jf>. '*Kvalimtim >f km d em iscr ttml p r n l r e l i v e crem i* l'or vvurUmim exposfiit tu im i w i t l uil." l i n i . ,1 Im i. M rd., 104.H, 5, 204. * IVoieihiue-v, I). I ... miti i n v i a , J . U. ,/, Ihpjir.ne. p n t h pivara). 1 Nan'yiwltiiaskii, SI. ,M. " Ulli'ftscniii Me li a ina omulnim*." i '/ilA;,n, M ila, {!), 22 li; hai. /'eira/., ISMI5, 32. 133A Ab, No. 2S). 300A (Abs, Ha l l ; l'i-iio h u m , 134(5. 9 . i 51. ave boon received, and initial frauuonaloruton Research Gontro by distillation rarmim and steam. All fractions are loved, and the course of mibse-queiit tel.ions will be. by methods least likely 1 active component present. The exact i hcmical .nr! petroleum interests. I t is tods to those known for following the f f nmnogenic components anil effecting listed with the American Petroleum arrangements made for the exchange e ATM. is embarking on a substantial .go \ sits of workers will be arranged, being done is cmnniensurato with the f .nd of medical research. It is sincerely Its leading to the elimination of onvirontry be concerned. Also, th a t Isnow ledge >,tills leading to the understanding and it left an exaggerated estimate of the taf effect is small even in the small oer Attention should be paid more to ( mthmous contact with oil, than to the lt> " touch pitch without being dofiled," i iv poisons m industry, it might even be th a t the persistent essful treatm ent of malignant tumours