Document VjBz0Z0oZ4y6MR2a26ggw4v7w

1 *>. tl. *7, >S . . -r,utn *. .. , . - iXs . ? & f\ ; < / :*. \ P Sbktvd-' vf AP00027563 Ir U* Recent Perspectives in Occupational Cancer BY IRVING J SELIKOFF /n recent years, many previously unsuspected carcinogenic agents have beenidentified and new perspectives established for the evaluation of the increasing numbers of chemical substances introduced into the environment. Attention is sometimes called to tbe fact that the first neo plasms for which etiological factors could be established, were occupational cancers. The report 200 yean ago by Perelvall Pott of cancer of the scrotum in individuals who had been employed as chimney sweeps <1), or that of chemical car cinogenesis in humans first described M years ago as `sniline cancer" (2), or that radiallen Induced cancer had an occu pational starting point among/ atom- he. Sehneehurg and loachimstal almost 90 TMSMMflKV* cited. These claims arc true, yet it is equally dBtdaeh ms an isolated de scriptive observation, of MjlMUllact in ha time. Accelerated ill 11 linwwjSreefB jieieertliia mature body of knowledge, the dhdptMfWMii|iBfliunl cancer, has rather been a matter of the pest two Acades. Although h was related to what went before by the continuing productive studies of the effects of ctrcinogenic aromatic amines (2), if on* event can he said to be the origin of this new phase, it may be the brilliant description in 1955 by Richard Doll of the association between occupational esposure to asbestos and an important risk of death of lung cancer (4). Doll's demonstration of the applicability of chronic disease epidemiology provided an important example for future research. Many of the concepts we now take for granted in the evaluation of occupational carcinogenicity, as. the need for long periods of observation 15), the utility of cohort studies (6), the possibility of co existence of cancer and other biological toxicity (7). were in herent in his classic report. Similar approaches have guided the best of experimental studies and have increased their relevance to human disease (5). With this background, a good deal has bean learned about occupational cancer in recent years. This has included identi fication of carrinogenic agents previously unsuspected of such effects and the eatabHshmcnt of a number of perspectives which are now available for the evaluation of other materials used in industry and/or agriculture or which may be intro duced in the future (9). The letter achievement is perhaps more Important, since the number end complexity of new or re cently introduced stents hat attracted much attention, and little is known concerning their carcinogenic potential. LATENT PERIOD The above term it perhaps inexact since wa do not actually know what it happening in tissues between the time of fits! exposure end initial evidence of clinical disease. Changes may be under way, albeit not detectable with current techniques. Perhaps 'period of clinical latency" or 'lapsed period" would be more exact < 10)- In any case, each of these terms describes an important phenomenon--that a considerable time must usually elapse between onset of exposure to an occupational carcinogen and the first evidence of resulting cancer. General ly, this period I* 20--55 years, although as little as 10--15 years may suffice, or 33--30 or mote years will pass. The time sequence can be affected by a number of variables touched on below, but it is remarkable how their influences operate with in relatively narrow constraints Understanding this, two conclusions become evident First, it would have been difficult or impossible to establish the carcinogenicity of substances widely introduced only in tho 14 AMIIO, VOL 4 NO. I past 30--50 yean, not be able, with humans of recent! three decades (11' from other discipl must elapse befoi ' designed to correc | effective. This he I smelter workers (I The importance haps nowhere beer associated with c Laboratory, we hr sulation workers. Union of such we January I, 197 (5 had died, almost were 27} deaths < anticipated. Anal) | cated that the to workers who had their work (Tablet The risk of lu asbestos could ea drawn, if studies i serve a sufficient : from onset of we | tained in studies o refineries (14) and cancers an seen 3-chIonnethyictbe: intense exposure o ! MULTIPUS FACT! I Investigations of generally seek to i able. Nevertheless carcinogenic agent complex work en substances of tins personal and soc I possibility of inter ; known in the exi i shown for occupel found among asbe , risk was not siguif not also have a hi had much more lu Asbestos exposure . risk of cigarette I asbestos worker w of death of lung same ago who n* The powerful nr agents can be asbestos iiuulatit established, the s was recorded; 95` a history of pipe ing, and 1437 . experience, with detailed in Table one lung cancer cember 31. 1972. ' only one lung can 179 lung cancer tie 1 smoking, although This, despite tha ft same trade, with e to asbestos. The significance action has many rs First, some subsla genic effect: in cc Such influence ma; there could also be substances now denew circumstances there may he mar AMBIO, ISIS AP00027564 in a ?r i il hu been leimetl about Hib hu included Idemiously nnsutfected of iuch i number of penpectiva hixtion of other neteriele or which may be introhkvement b perheps mote xtmplexlty of new or ra sed much ettention, end isogenic potential. since we do not actually between the time of first ical dbcue. Changes may with current techniques, or 'lapsed period" would fa of these terms describee . considerable time mutt rosure to an occupational resulting cancer. Generalbough as little as 10--15 s years will pass. The time er of variables touched on ir influences operate withms become evident. First, npoasible to establish the j introduced only in the Ausso.yca.4 no. i past 30--50 yean, until the last decade or so. Second, we will not be able, with present knowledge, to identify cancer risk in hugunt Of recently introduced agents for another two or even tiuw decadeg (II), and apidemiology mutt look to assistance free# other disciplines. Parenthetically, a similarly lone period mult einpae before it can be ascertained whether measures designed to correct an occupational cancer hazard are actually affective. This has been the case, for example, among nickel smelter workers (12). The importance of the principle of clinical latency hu per haps nowhere been better demonstrated than with lung cancer aaiociated with occupitional exposure to ubestos. In our Laboratory, we have been following a cohort of asbestos in sulation workers, composed of all 17 800 members of the Union of such workers in the United Statu and Canada on January 1, 1947 (J). By December JI, 1972, 1356 of these men had died, almost 400 more than had been expected. There were 275 deaths of lung cancer, whereas only 56 had been anticipated. Analysis of the work history of these men indi cated that the excess deaths were largely limited to thou workers who had achieved more than 20 yean from onset of their work (Tables 1 and 2). The risk of lung cancer with occupational exposure to asbestos could easily be missed, and inaccurate conclusions drawn, if studies are made without the opportunity to ob serve a sufficient number of individuals 20--30 or more years from onset of work exposure. Similar result! have been ob tained in studiu of uranium minen (13) and workers in nickel refineries (14) and with other egents; indeed, when many lung cancel* art seen after significantly shorier periods, u with 4-chIonnethyletbcr (15), one might justifiably suspect rather intense exposure or particularly virulent agents. MULTIPLE FACTOR ETIOLOGY Investigations of occupational exposures for carcinogenicity generally seek to isolate the suspect materials. This Is reason able. Nevertheless, this approach is in a sense artificial, since carcinogenic agents arc infrequently used singly, but rather in complex work environments, often with a variety of other substances of unstudied potential, and by individuals whost personal and social environments an equally varied. The posrihiUty of interaction of two or more (gents has long been known in the experimental setting; since 1968 it has been, shown for occupational cancer in humans as wed (16). It sees found among ubestos workers, for exempts, that lung cancer risk sis not significantly increased among thou men who slid not also have e history of dssrette smoking. Thou who did, had much more lung cancer than cigirette smokes* in gcacral . Asbestos exposure thus markedly increased the lung cancer risk of cigarette smoking: it has been calculated that an asbestos worker who smokes cigarettes hu 92 timet the risk of death of lung cancer compered with an individual of ths aune age who neither smokes nor works with asbestos (16). The powerful multiplying effect of the combination of two agents can be appreciated by examining the experience of eshestne insulation workers cited above. When the cohort ns ettehlhliod the anokhtg habits of the majority of the workers was recorded; 9390 had n history of cigarette smoking, <09 had a Mmery ef piee andfUe cigar smoking but no cigarette snok- wo never smoked at alL Their mortality ; with amici)fer reference to lung cancer, is Among those who never smoked, only ***** was sees from January 1. 1967 through Dn- IfTZ* The pipe end cigar smoking group also had j cancer death* On the other hand, them wen | cancer death* among those with a history of cigarette j although only 32 such deaths were expected to occur. This, despite the fact that ail of these men had worked in the seme trade, with equal opportunity for occupational exposure to asbestos. The significance of the principle of multiple factor inter* action has many ramifications. Two are of Immediate Interest. First, some substances, by themselves, may have no carcino* |tc effect; in concert with others, malignancy may occur. Such influeace may be additive or multiplicative (theoretically, there could also be a protective effect, as well). At a corollary, substances now deemed innocuous may change their habit in new circumstances; our vigilance must be constant. Too, since there may be many more substances of limited carcinogenic potential than those individually capable of inducing malignancy, and since at least some working environments now tend to become more complex, this may turn out to he of consider* able practical importance in the future. Second, animat studies generally are directed to the inicstigation of one agent; negative results may therefore be mis* leading insofar os actual work risk is concerned. (To com pensate. one should hasten to add. dosages can be far greater than those which occur in industry, and carcinogenicity en hanced). SIGNAL CANCERS Most occupational cancers are identified as occurring as in creased numbers of common malignancies. Thus, increased rates (taking age, year and sex into account) of lung cancer occur, for example, with occupational exposure to talc, chronutes. arsenic, nickel carbonyl, uranium mining, fluorspar mining, hematite, /f-chlormethylcther and asbestos; of biad- Table 1. lipidsit and ibstiwt deaths among 17 mo asbestos Insula te* wortnro fc the netted gtttse ted Canada January i, iM7-oecaaw been, 1171. Sweden from see#! ef expeewe Un Sian N years Mere Owa 10 years --MSlati* Observed bpsslir Observed Tettl deems--eM sauces Caneer all aftoo Long oeneer Aabeatetle All other ewises Master af pareaae JBM9 *4f 0.40 --* 171.40 e< SO r 170 11 HI ffioia no* 9M m--m til M7 mHt * stio _____es ere baoed upex aoe-tpsoiM whrtt male doom ret* data of ms US National Office of Vital Itsttstfea. Setae far ffifl ware eitrw Cslated tram rates hem 1997--1471. rates are nas available, but mesa are rare eawaee ef death In the general peculation. erttara in the US aad Owed*, January 1, imp-December si, wa* fatedan la elapsed parted Sens aneet ef went exposure. 1 i1 <10 d-ti 40-10 SO-to ae-ae S0-4S ss-ae as 40--40 a+ Tetai spotted deeds* ass ijr 1.0 ji ie.rt ji 4JI 4J4 4JP1 mm Lena sanssr Observed oils < uu snVo IS a 271 ItaUa 2.1 a 3.1 9.2 74 M sa 4.2 4.4 4.0 * bpesssd deaths are based upas aae*apeefflc while male death rata dau < the UC National Office et Vital statistics. Rates ror 1972 ware extra* fable S. Ixpaeted and shoenrad deaths ef Kin* eaneer ament 17Mt US end Canada aabeatee Insulation workora, January 1, 11*7--Oeceasbar *1, ISA; retells* ef cigarette smoking. History e< pipe and/or cigar only SasM 144 Mat 20M 1407 909 I s DasSia Iram lung eaneer OhaarviO Ratio 11.9* 44 s. 31.99 179 17 7.51 2 11 4.40 1 0.2 111 1 0.3 Iraeetsd deaths baaed upen ege-eeecifie US mortality retee ter wtiite mates disregarding smoking. Lung cancer estimates based upon US rates tmIotsr eaneer ef lung, pleura, brenehoo and trachea, categories ReefvtihsieonI.nternational Classification of 01eatsas and Causes of W and Deaths, AM]IQ. 1973 15 AP00027565 der oncer with 0-MphthylaniM and benzidine; of leukemii with benzene end radiation. To find the effect of such sub stances. appropriate population studies ate necessary to see if the expected background rates am increased. Sometimes, espe cially II less common tumors ere being considered, at brain or adrenal or kidney or lymphoma, extensive observations ire necessary, if not of moderate sized groups over long periods of time (after the 20 year point!), then of very large groups for shorter periods (to achieve an adequate number of 'personyears" of observation). In a number of instances, unusual tumors havu bean ob served in considerable numbers for which the usual expectedobserved ratios are almost superfluous When cancer of the scrotum occurred among Pott's chimney sweeps the absence of biostatistical calculations did not prevent recognition of the unusual situation. Sinus tumors among woodworkers may be looked at In somewhat the same light (17). Two neoplasms, infrequent in general but common with industrial exposure, have demonstrated that such 'signet" tumors can be important factors in identifying occupatianel carcinogenesis. One, hemtngiosarcoma of the liver, has as sumed such a role recently and will be discussed below. The second, mesothelioma, hat a longer history. Rest reported in the pleural cavity of an asbestos worker in 1937 (II) and in the peritoneum of another the next year (19), its link to asbestos was firmly established in I960 (20) when, in a series of 47 cases in one laboratory in South Africa, over a five year period, 43 were shown to have had opportunity for asbestos exposure of one or another type, decades before. The imped of this finding can he gauged by appreciation that, in general, approximately One in a thousand deaths in the general popu lation had been known to be caused by these previously un common tumors. With occupational asbestos exposure, these tumors have proven common (21). in some cohorts of asbestos workers, approximately five or six percent of deaths have been due to pleural and peritoneal mesothelioma (5). In others, the percentage it lower; it hae been reported, for example, that this neoplasm it less frequent among Quebec chrysolite asbestos miners (22). When found in family contacts, it led to the understanding of the danger of bringing dust from the factory to the home (23), when found imM residents in the neighborhood! about aebestot plants, it bespoke un controlled asbestos sir pollution in the past In South Africa's large series of cases, with adequate history, only approximately fifteen percent have been judged not to Have had some known asbestos contact (24). Thus, wherever mesothelioma it found, asbestos is sought. In this way, otherwise unsuspected oo cupstional exposures to asbestos have, been identified--in ship yards, especially (231. ENVIRONMENTAL CANCERS FROM OCCUPATIONAL SOURCES Ah important dimension was added to occupational cancer with the discovery that neoplasms might occur with the dis semination of the agent beyond the factory gata. either by its release during the manufacturing geeceee or from roulting waste, or by contamination sfhoeaabolde with tha offending material being brought honed kKjWttjMn* clothes. Although instances of such disease UUiljiWi btfori (20L th* full import of the problem wt*J3|^BBi|NbasduntH Newhouse's report in IMS (23) whLdmOBMi*pt9d that, of 7 con firmed cases of mesotheRema Ijfjjkk fata of lha London Hcapitsl, of the 43 not know* to fMdkllefr occupational exposure to asbestos, nine had simply lived in the households of asbestos workers ('conjugal disease") and 11 had neither worked with the material nor lived with someone who had been so em ployed, but had resided, many yean before, within one half mile of an asbestos plant in London. This finding was soon confirmed (2d), and the principle of carcinogenic risk derived from occupational sources is an important factor in current evaluation of control of environmental cancer, whether it be from radiation-producing power sources, agricultural use of pesticides, air and water pollution from petrochemical industry operations, carcinogenic mineral dust, or other substances or processes (II). These considerations arc separate from those involving cancer risk with end-product use, either during further industrial manipulation of materials or in utilization of consumer products. PETROCHEMICAL INDUSTRY CANCER There was a curious discrepancy during the first half of this century between continued concern regarding the potential for occupational cancsr in the burgeoning petrochemical industry and reliable evidence that this wes occurring with eny fre quency. In considerable pert, the contradiction remains. On the one hind, the industry deals with a very lerge number of chemicals which either have bean shown to have carcinogenic potential in laboratory animals, or are related to these chemi cals, belonging to such suspect groups as the polycyclic aroma tic hydrocarbon! or some of the helogenated hydrocarbons; in several instances, as benzpyrene or ^-naphthylamlne, occupa tions! cancers in humans have been clearly established. On the other hand, the number of chemical agents so incriminated hat remained comparatively small and the number of workers involved, limited. With the recent ideitification of vinyl chloride induced cancer (27, 21), the situation has changed somewhat It ia still not known whether a good many of the petrochemical industry's materials will turn out to be carcinogenic--in large part, an adequate 'latent period" bu yet to run its course, to allow for proper evaluation. Still, to find that a key chemi cal in the giant plastic industry was clearly carcinogenic has bean disconcerting. Further, it was sobering (a realize that if vinyl chloride's carcinogenicity had been expressed in increased risk of cancer of lung or colon, elevated razes of neoplasms of these sites among the affected workers might not have been identified for some years, at the earliest. The fact that it was in unusual tumor, hemangiocarcotna of tha liver, otherwise rate in the general population (perbapt one in 10 MKT--40 000 deaths), which occurred, attracted attention. Three eases in one plant, the B F Goodrich Company in Louisville, Kentucky, were sufficcnt to establish a itrows sink piooo of die risk (29) and tha suspicion became a virtual certainty when the same neoplasm was found in other vinyichloridc polymerization plants, making vinyl chloride the likely offender, rather than other coexisting chemicals, ea special additives or process chemicals, peculiar to the Louisville plant's operation. At the sum time, the fact that only a dozen and a half cases came to notice in the first five months after discovery of tha condition did little to allay concern, since these case*, when analyzed, had begun work, on the average, approximately 20 yesre before death, at a time when the vinyl ehioride-poiyvinyi chloride industry was limited in size and still employed relatively few workers. Of the 19 esses recorded by mid-Junav 1974, 15 had begun work 1944--1932, with an overall average of 20.4 years from onset for the group aa a whole. Since the great majority of workers in vinyl chlo ride-polyvinyl chloride plants were first employed during the 1930b end i96Qx It was evident that the full impact of vinyl chloride tumors would not be known for another two decades. Limited data to far availablt suegrets that, at least for poly vinylchloride polymerization workers, the incidence of oc cupational cancer will be sicnifkanc We have examined the mortality experience of n cohort of workers employed nt n large polyvinylchloride polymerization facility in thz United Sates The plant opened its 1946 and from that year to 1963, 237 individuals were employed in the production process for five years or more. While ezpoeurea began in 1946, relatively few individuals were employed prior to 1951, when t significant increase in the work force took place. Thus the majority of the cohort hex had a bare 20 years or iesa from onset of exposure. Aa initial report of the experience of these men hex been made (30). We have traced each of the 237 individuals to December 31. 1973. Twenty-five were found lo have died, of all causes. Three of the deaths, each confirmed at autopsy, were due to hemangiosarcorna of the liver (Table 4). Ages at death were 41, 54, <0. Elepaed time from onset of first expo sure to death was 14,17,23 years. OOSE-OISEASE RESPONSE RELATIONSHIPS Discussion of this thorny question, with social, ethical and economic implications co-mingled with scientific perspectives, was stimulated and made much more acute in the evaluation of regulatory measures necessary for the control of vinyl chloride cancer. While it has been generally agreed that the risk of malignancy increases with intensity end duration of exposure, there has been much less concordance in the evalu- 16 AMB10,VOL4NOl I Table . Causes M t ler I er were years. ClRfff Ml lH H-- HmmlawcQf*Mi li Neoplzime cf lymph* Bum fOilebtaeleeiel Peecrvee Colon Clntiesle Mth eseshat Csngnesnuar Oweiel atlqn of whether e i would not occur. 77 this aspect of the q | be that suds data meats, to be conv I numbers of animal! large numbezi of longed periods of t the monomer. Eve mould always bo a coeczivsbiy could | would seem So ini [ threshold limit for regulations for the chloride in the Un from this point of been proposed (32 l might be considers allows for inevital occur in the Indus of practical probien of the work environ PRETESTING OF Recognition of tha onset of exposure to ! end their carcinoge raised the corollary evaluation and shcr ty. Much attentio recently, however Although itractu occasion a high !> necessarily follow known. Further, with biological tc with toxic effects tem, without conce Experiences wit suggests, however, for at least some a* were able to cstablt stance which was la 33). ft is not known proaches will be ec whether other latx studies, will extend hoped for and mud mation on the quest: for selection of agen include such eonside other biological act exposed. For subsist could apply, with tl studies should be tug workers whose expos AMBIO. 1975 AP00027566 :eh ing the first half of this rgarding the potential for g petrochemical industry occurring with any fre>ntradiction remains. On 1 a very large number of van to have carcinogenic e related to these chemii as the polycyclic aromagenated hydrocarbons; in )-naphthylmine, occupalearly established. On the gents so incriminated has the number of workers r vinyl chloride induced thanged somewhat. It is tty of the petrochemical be carcinogenic--in targe as yet to run its course, to find that a key chemi- clearly carcinogenic has .obering to realize that if ,en expressed in increased ted rates of neoplasms of cn might not have been iest The fact that it was a or the liver, otherwise tpt one in 10000---40000 tntion. F Goodrich Company in to establish a strong su spicion became e virtual ns found in other vinylking vinyl chloride the coexisting chemicals, as peculiar to the Louisville the fact that only a dozen he first five months after : to allay concern, since uq work, on the avenge, th, at a time when the ustry was limited in size .orken. Of the 19 cases begun work 1944--1952, from onset for the group of workers In vinyl chlo'irst employed during the : the full hnpact of vinyl for another two decades, ts that, at least for polyrs, the incidence of oc- We have examined the f workers kmployed at a :n facility in the United d from that year to 1963. te production process for began in 1946, relatively o 1951, when u significant ce. Thus, the majority of rs or less from onset of e of these men has been )f the 257 individuals to re found to have died, ot eh confirmed at autopey. e liver (Table 4). Ages at from onset of first expo- flOIttHIPS with social, ethical and hh scientific perspectives, -e acute in the evaluation for the control of vinyl generally agreed that the mtensity and duration of concordance in the tvalu- Aim, 9014 NO. I mm mm ~':h Tama 4. reosea at deem snene SS waafcaia aspaaad ta vteyt aAiadda ter eersmee yean. 1. r ran, Omrqfrar ScrwuM, CMnr|4rar OSwrvlriMi (Hssvs Chit sad Cbd- teain ll htiM Ungi. lawdaa. I TO) ff SS--44. S 2. t C Arw aad M f Argw. CMadrar WWvTUa tfCmm (AxwWmU hw New HWMWilOMrCOdTH Of llvr NaanUem Ivswbuie and baoiahonolaiie ilaauw Brain fdllaMwtomcl Nnfh 00<OA Boa* Ctfrnt (with GODng) VBfiCW) Fwi >Mraihra biMdlira (OoWtthiwi* 9 YeA,ir?4)VWIIpyJ-<. 7 3. A EircAaaaad H SikJ, Aawrvwi /auma/OfCouir IL ttl (1*32) 4. a Dei, out *wiwr <ydMhwrtarsMnwii.il (ills) 1 I. IJ StSkaTT. C HiiamwS aad H SeiSwaw ia SWIosfcv/ JJfKtt afAlhttte*. r 1 taswehi. J C OiUaa. V IlMbwCand J C Warner. Ed1 (laurwiioail Aamcy Xe- 1 M4fea OM Cuccr. Lyaa. 1473) pp 204--<14. 4. T X XUacUM xe4EJ Coulter, ArrAAw of t 7. t 3 SelkVt. 3 Ow|MM IC HXmnoW, 1 dan 1*23(13343 Huhh 4 (2k lid (1345) iAdWaTAawrw i a JCWasnw.O aany.f WSUdaiantW VTIaUerlL MV/iMyC4a>>. CaratovkMwidr 4ii*iiN, t4 332(1374). 3. 1C Kasnend aad 11 Salikoif. id dnaiyrtr md EmariaamM/ EpMtmtolofy </ Cmetr, W Nlkaban. T Hinraum. K NUdofca aw H Sasano. Ede (UMtandy V Takya Pfwa, lapa*. **73) PP 41--4*. m 12SaSkatf and SC Kanawad, OnWawnwuai JtaaaarcA 4<2) 8-41(1371). II. MSafikadTaad EC Haawoad, AacaViiasrdfVWrrAVa/MM/CkararCw^r- WMt.LwAaeUai, 4X7(1373V IS a Dad. L O Mafias aaS 3 e Spaiaar, JrtlUA Jbianar ay Cadcar XXJV (4). 433 turn 13. f I LwUnir.) W Uojd. E M task. V E Aratw tad A Holiday. Head* /b)*n 14,371(1343). Id X Padaiw.A HapdoMtaad A Awtanaa. IwwmwrLiaaiJowwa) ycwwv.U.32 ttion ot whether a lower threshold existed below which cancer would not occur. Then have been few data bearing directly on this aspect ot the question and, in the nature of things, itmight be that inch data art unlikely to appear. `Nsgsttva" experi (I37IV U. w o Plgnraa, H KaahaavAi lad W Waiw Alnr Pi1-- J "r--I ' V Vidriaa asaiv loHori), M. W SW2ddf. t C HaswosS aad J Cbwg. AwafflAr Aawrttwi VadtcV Aa<artaWw2M(2). 104(1344) ments, te be convincing, would have to involve very lerge 17. ID *rkawa. XHCawWSwS axa4.eaaahXiMa<(yuAaw<WedMir33. numbers of subnets and, mom important, observation of very 31(1374 large numbets of vinyl chloride workers exposed for pro 34 Awaiw. tiadrsyicarA3(135% I I longed perloda of time at measured low levels of exposure to the monomer. Even if these dele should hi obtained, they 1*. 71 wahar.ArtAr.dk CrweraeAWoaW wWO>evrtW>)WWw.ta**2(iaS<). 3h 3C3Vaeaar,CAghmaa4EMaaxAaa4.hAAW/4unwrqflaahwrtariradk4< I7.2SC(I3M*. would always be only an approximation, since further study 21. JtIaliaiwnaa4WJMtaar,JW2l,2g(IM. , cooctfvabiy could show exceptions. Theocsticai considerations ia )C UcDaaaM. X MrOaaala.O W-)I| ' ltiai.|ili wl ~ 2hi linr.Ao would item to indicate that than la no identiflabla lower a*lwt<ynwkaMa--V MmUXL477(1371) | threshold limit for carcinogenic agents <5tv The proposed regulation for the control of occupational exposure to vinyl chloride in the United States seem to approach the problem from this point of view; a level of one pest per million has bees proposed (32) which, interpreted in practical tana, might be considered a *no threshold" level but one which ZL tdm--Uaaw asSRTUlwiiii. .WWahAwwaraflAimif VMliSwZLJSI (1*43) 34 1 Wataur. SawA AAMwa ahdhal JhwnM S3 (2), 1U (Itnv 31 PO Hairhw AawaA at OKMMrtaaar t)|lw IS. 133(1341), 14 J Uatw aad H rianWa, ArtATaw eynwAmwawS/MwM K 333 (IIS7) ZS. iLVlala. A Wgaslaad ACaswwCkwew daw Ui3L 514(1371) 3a C ItalMid aad QI WhwWa nwaawwawM twrrl 7.741 (1374) allows fee mevitabia mistakes tad accidents which might 14 2 L OnwA aad M H Jalawaa, AMmal afOangartMar-Vadnaa M, I3S (1374) occur in the industrial environment, as well as iwcognition 14. W 2 NUMaaa. n SMWwav IC HvwwwS lad 12 laStad. AwwA rfMto TwA of practical problems concerned with instrumental monitoring Aawhw/qffrtaww Wanw of the work environment. 2L SwAwdw <y aawwwwMar iwrtaasBW SapM ta tha Sargsoa Oaaeia) I PRETESTING OF NEW MATERIALS OIPRS.Aadl2Lt97e.A4RaeCawwlttwataaEvt)wthamafLavLa<nlaafla. drawsawUI ChaMhai CtacWesww 3t (ansawMyf,4w(Vnsi<<fi|>i7--(SaUawwaaiww rwa Recoinhind of the long period of rifnknl latency brtwuta waa m MayarAhwMWanawaUaaar <w*<r wadAaatA awadnb (Eadan) Hasjww onset of exposure to meterials in the occupational environment 3453330--33434OcwAw41374) tad their carcfatogtnk effect, if this is to occur, hex recently raked the corollary question whether ws might anticipate such evaluation end shorten, or eHminata, this period of uncertain ty. Much attention is now being paid to this peesibUity. Until nceady, bowevur, expectation end desire exceeded promise. Although structural similarity to known carcinogens might 33, S L Vae Owiaw M CiUuowMl. C Earn L LiaQi'h. C Uanarta aad A RwA, ArtAWwy*n*wmmaar MwM 14 4n(l*M) 34 U Saaaag, A laWawna. C Xawa) C A WlrtwwMUr Awiia J, 134 (ird) 53. Kawwtk wjyaiMd hy3U* EX 00321 oftlr Nadaaal laalluii af Eaviraarwaaia* HwntaiwiwBdhyrtwBavkeaiwalalCiaBMaaawixaPieiaaoflluAwad. aaaCaaoaSaawiyU-354 titmdnu n Ugh leva! of sutpicsos. cancer potential does not Warsawray follow structural resemblance; many exceptions an known. Wrthar, whSe saagdritm could be directed to sgents M kahglril activity other than cancer, many ere known " t,effects as kidney, liver, lung, central nervous sye- S concomitant reeognfacd cancer potential. Ska with vinyl chloride and jS-chlormethyiether r however, tint laboratory screening might be feasible. ' dt gome agents, ha each instance, laboratory studies l a* mtaliUsh the carcinogenicity of a chemical rub- l which was later shown to be carcinogenic in man (21, 33). It is not knows whether such experimental screening ap- proocbm wV be equally productive with other agents, nor whether other laboratory techniques, including mutagenic studies, will extend their utility (34V Certainly, (hie is to he hoped for and much work it being initiated to provide infor mation on the question. Guidelines that would point priorities for selection of agents to be tested ate also being discussed, and include such eonsidentiom is chemical structure, evidence of other biological activity, number of workers likely to be axpemd. For substances already in use, similar considerations could apply, with ths added dimension that epidemiologicat studies should be suggested when there art avtaabic groups of workers whose exposures began 10--15 or more yean ago. AMMO.W73 'pjuinjwiiai... ^>'5** TV-' AP00027567