Document 065oeeZxExVwxM2bpNZrzmGOx

-O IA ? OCTOBER 1969 VOLUME 100 NUMBER 4 AMERICAN REVIEW OF RESPIRATORY DISEASE Clinical and Laboratory Studies of Tuberculosis and Respiratory Disease Utual Dilution V.3 with Saline r cr other diluent--rj 1 :3 with Saline ' or other diluent Undiluted t -vYork, N.V. 10015 ASBESTOS AND HEALTH IN 19691 2 GEORGE W. WRIGHT Although a group of materials referred to generically by the term "asbestos" have been known and used, to a small extent, far back in antiquity, widespread and abundant use of these fibers did not begin until the last quarter of the nineteenth century, with further augmen tation of production during the first half of the twentieth century. There are six distinct varieties of asbestiform fibrous minerals. Among some of these, there are striking differences in chemical and physical composition (I). Most commonly produced is chrysotile, a member of the ser pentine family. The amphiboles are subdivided into crocidolite (blue asbestos), amosite, anthophyllite, tremolite, and actinolite. All are silicates, crystalline in nature, and characteris tically are divisible into very small fibrils. Chrysotile and anthophyllite contain much larger amounts of magnesium than either crocidolite or amosite, and the last two contain much more iron than the others. The crystalline structure and surface properties, which may be of importance in the biologic reaction, are also strikingly different among the varieties of asbestos (1). In view of the great variation of chemical and physical properties, it is most un safe to predict that the biologic reactions of one variety of asbestos will be mimicked by another in terms of either actual consequences or mech anisms. To interpret the biologic actions of 'From the Department of Medicine, St. Luke's Hospital, Cleveland, Ohio. ' Presented before the Medical Session, as part of Section 3A, at the annual meeting of the Ameri can Thoracic Society, Miami Beach, Florida, May 25, 1969. asbestos, it is imperative that the character of the exposure in terms of concentration, size, and types of fibers be known. This sort of data is scant or often nonexistent at present with respect to exposure of humans. Pulmonary fibrosis: In 1907, Murray (2) re ported the first cases of diffuse pulmonary fibrosis discovered among a group of persons who had experienced substantial and prolonged exposure to respirable-sized asbestiform fibers. Subsequently, the term "asbestosis" was applied to this reaction. Traditionally, asbestosis has connoted this kind of reaction and its sequelae with regard to altered pulmonary and cardio vascular function. Recently, the term has been corrupted to include such manifestations as pleural thickening, pleural plaques, and even the simple presence of ferruginous bodies. Resolution of the use of the word asbestosis must be ob tained to bring clarity to scientific reporting. Murray's report revealed the paradox of a life saving agent possessing the capacity for human harm. At first, the conditions under which this biologic reaction came about seemed to be re stricted to those created during fabrication, conditions limited to textile manufacturing at that time. In 1930, Merewether and Price (3) demonstrated that asbestosis posed a major threat to the health of workers in the asbestos textile trade. It is now known that in any of the several trades in which persons experience pro longed exposure to a high concentration of respirable-sized asbestiform fiber, it is probable that some of them ultimately will develop pulmonary fibrosis. In response to the report of Merewether and A m e r ic a n R e v i e w o f R e s p ir a t o r y D i s e a s e . V o l u m e 100. 1969 467 L. r *tr~ "S'1 468 ! GEORGE . WRIGHT Price, the fabricators of asbestos-containing products took substantial measures to reduce the concentration of airborne fibers in the fac tories. The report of Sayers and Dreesen (4) in 1939 further stimulated the introduction of such corrective measures, especially in factories of the U.S. and in mines and mills of Canada where 95 per cent of the free world's asbestos was produced. Regrettably, substantial numbers of persons exposed to asbestos in their occupa tion have never come under a protective occu pational hygiene program. Insulation applicators and some individual or small business fabrica tors fall into this category. The preventive efforts that were applied led to considerable improvement in the factories, mills, and mine environments and a subsequent less ening of the occurrence and severity of pul monary fibrosis. Unfortunately, the relaxation of precautions governing occupational health, common under the stresses of World War II, seriously interfered with many health protection programs, including that for the safe use of asbestiform fibers. As a result, the protection of workers using asbestos in mining and milling and especially in factory settings has not been as good as it might otherwise have been. Until quite recently, the threshold limit value (TLV) for environments containing as bestiform fibers suggested tentatively by Sayers and Dreesen (4) in 1939 has served as a guide. Data entirely adequate for the purpose were not available in 1939, and it has taken years to recog nize this inadequacy and to obtain the informa tion upon which to base a more meaningful TLV. Fortunately, one of the major users of asbestos in the production of textiles and textile products has pursued for many years a program of en vironmental and population monitoring that now provides a more up-to-date experience (5, 6). These studies demonstrate that pulmo nary fibrosis can be minimized when adequate protective measures are instituted, and that the concentration of airborne fibers must be the focal point of attention even though the tech nology of such monitoring may be new, difficult, and expensive. The U. S. Public Health Service, which began extensive studies into the problems of asbestos and health in 1961,' together wfith asbestos producers and manufacturers in the U.S. and Canada are at this time examining 'Cralley, L. J.: Personal communication. their experience with population exposure and pulmonary fibrosis during the past 30 years. It will be of interest to learn how their findings compare to those of the United Kingdom. A provisional TLV expressed in concentration of respirable-sized asbestos fibers has been set re cently in the United Kingdom, and a slightly dif ferent value has been established in the U.S. (6, 7). Whether these are proper for all varieties of asbestos and all settings in which human ex posure might occur is debatable. There is con siderable evidence to suggest that chrysotile penetrates to the deep lung spaces less readily and is cleared from the lung more readily than either amosite or crocidolite (8). Also, chryso tile causes less pulmonary fibrosis in experimental animals than amosite or crocidolite (9). With regard to the prevention of pulmonary fibrosis, one would conclude in 1969 that in many settings the maasures taken have not been adequate, and there are populations that have had little or no protection at all. The knowledge required to protect all workers is not available at present, and its development is one of the urgent tasks of the immediate future. Neverthe less, an important step has been taken toward further defining the conditions necessary for the prevention and ultimate abolition of significant pulmonary fibrosis in persons exposed to as bestos fiber. Bronchogenic cancer: Although in 1935 Lynch and Smith (10) reported bronchogenic cancer in 2 patients with asbestosis, it was not until 1947 that the possibility of this second biologic influence of asbestos fiber was seriously raised, when Merewether (11) demonstrated bronchogenic cancer in 13 per cent of autopsies of persons who had asbestosis arising from em ployment in the textile trade. Eight years later, Doll (12) reported a frequency of lung cancer of ten times the expected rate in textile workers exposed for at least 20 years, during the period between 1922 and 1953. This experience has been confirmed in the textile trade by Newhouse (13), Enterline and Kendrick (14), and Mancuso and El-Attar (15). More recently, Selikoff and co-workers (16) reported a frequency of bron chogenic cancer eight times that anticipated in a group of insulation workers employed for more than 20 years who utilized a substantial portion of their time removing old or applying new insulation that contained asbestos. This . >i iI series of play an frequenr. gories of however, substanci environm exposed that r<v genie pot prudent before at nogemc i; In a-be primarily crocidolit* applied t Moreover fibers, a . of metalfluences i (19-21). Insula ti only to c-1 daily in of their v i apply ne\ workers t* of which the ashest sulation u< details of have inhal* Of the posed con and brow are of imr the infirm* variety of involve cc ing upon t in no instat Data cor tionships c most stron. genic cane* insulation most ins-t.i' trade for : Price (31, port an ir fibrosis) ir* I i upmW iW jjjw w p -y.i'.'^-lfejLgte..'., * if$ { h k ir *>8 * l ^ A * 5 o * --.iiS . __ rig^jgiifwi r!r>:r f 1^ i . -V-rib-> Jtlgk.V 3fraA .fo ,,. exposure and st 30 years. It their findings l Kingdom. A mcentration of is been set re i a slightly difd in the U.S. 'or all varieties ich human ex There is conhat chrysotile es less readily e readily than Also, chryson experimental 3 0 ). of pulmonary 1969 that in have not been ions that have The knowledge 3 not available is one of the ure. Neverthetaken toward ees for the i Oi .nificant xposed to as- ugh in 1935 1 bronchogenic isis, it was not of this second r was seriously demonstrated nt of autopsies ising from em;ht years later, of lung cancer textile workers ring the period rience has been sewhouse (13), and Mancuso y, Selikoff and lency of bron- anticipated in employed for 1 a substantial ild or applying asbestos. This ASBESTOS AND HEALTH IN 1969 469 series of reports suggests that asbestiform fibers persons exposed for 20 or more years. This indi play an undetermined role in the augmented cates a heavy and prolonged exposure to asbestos frequency of bronchogenic cancer in some cate for these two types of worker. Knox and as gories of workers. In none of these categories, sociates (5), in a continuation of the study of however, has there been a full exposition of other textile workers previously reported by Doll substances which coexist with asbestos in the (12), show that the incidence of lung cancer environment and to which the worker has been decreases with progressively smaller total ex exposed (5, 6, 17, 18). It is possible, therefore, posures to asbestos fibers. Newhouse (13), also that coexisting materials possessing carcino in an asbestos textile population, has shown genic potential might be implicated. It would be that the occurrence of pulmonary cancer differs prudent to explore this possibility thoroughly markedly with total exposure. She reports no before accepting asbestos per se as the carci increase of the incidence of bronchogenic nogenic factor. cancer in a low to moderately exposed group, In asbestos textile mills, the exposure involves whereas in a heavily exposed group the inci primarily two varieties of asbestos, chrysotile and dence was augmented eightfold. Both groups crocidohte. In some factories, oil has been were from the same textile mill and were similar applied to the fibers before final processing. with respect to duration of exposure and the Moreover, in the process of "opening" the length of time of observation. Enterline and fibers, a strong possibility exists that traces Kendrick (14) demonstrated a stronger rela of metals known to have carcinogenic in tionship between lung cancer and employment fluences may have been added to the fibers in the asbestos textile trade than exists in the (19-21). less dusty manufacturing of asbestos building Insulation workers have been exposed not products or building materials. In a series of only to chrysotile and amosite but also, espe studies, Mancuso and El-Attar (15) suggested cially in shipyards, to crocidolite. The nature that cancer risk is lower with lesser exposures of their work, as they remove old insulation and to asbestos. From these observations, the in apply new in various places, exposes these ference strongly favors a dose relationship be workers to many nonasbestos substances, some tween bronchogenic cancer and whatever effect of which may be hydrocarbons adsorbed onto asbestos fibers may ultimately be shown to have the asbestos fiber. The exposure history' of in in its causation. sulation workers is seriously lacking as to specific The question of whether the carcinogenic details of all of the materials that they may role of asbestos is related to the specific kind of have inhaled in addition to asbestos. fiber is more difficult to answer. For this pur Of the numerous questions which could be pose, populations having long-term exposure to posed concerning the relationship of asbestos only one variety of fiber are needed. Virtually and bronchogenic cancer, the following three all fabricating processes use more than one are of immediate practical importance: (1) Is variety within the same premises at any one the influence dose-related? (2) Is it related to time or have used more than one variety at variety of asbestos? (3) Does the relationship various times. Populations restricted to mining involve cocarcinogenesis? Some evidence bear and milling in the production of asbestos fiber ing upon these questions is now available, but lend themselves best to a study of the effects in no instance is it complete. of a single kind of fiber, and it is to these Data concerning the question of dose rela populations that one must look for an answer to tionships do exist. The type of work related the influence of a single variety of fiber. most strongly to the development of broncho Kiviluoto and Meurman (22) showed that genic cancer has been in the textile and the exposure during the production of anthophyl- insulation applications trades; the worker, in lite in Finland carries with it a threefold to most instances, has been employed in either fivefold increased risk of bronchogenic cancer trade for 20 or more years. Merewether and for those in the age group older than 45 years Price (3), and Selikoff and associates (21) re with more than 10 years of exposure. At this port an incidence of asbestosis (pulmonary time, there are no published data with respect fibrosis) in these groups of 80 per cent among to the frequency of bronchogenic cancer in the r IL i 470 GEORGE W. WRIGHT crocidolite or amosite production areas of South Africa, the only place in the world where ap preciable amounts of these types of fiber are produced. A verbal report* from South Africa suggests that the frequency is somewhat higher than anticipated in the general population of that country. Data from these regions will be awaited with great interest. In 1958, Braun and Truan (23) reported a study of the frequency of lung cancer in workers of the mines and mills producing only chrysotile in the eastern part of Quebec, Canada. From the data avail able to them at that time, they found no evidence of an augmented frequency of bronchogenic cancer in this group of employees. Although the period of observation was only five years and the group was diluted by short-term exposures, it contained more than 1,700 persons employed longer than 20 years, all of whom had had at least five years of exposure and 930 of whom were older than 55 years of age. The data would have been more meaningful if arranged in terms of total exposure and time from beginning of ex posure. Nevertheless, if an excess of lung cancer equivalent to that seen in the settings referred to previously in this paper did actually exist in this population, it seems likely it would have been found. This same population is now being restudied after a much longer period of observation and in a more adequate way. Vigliani and associates (24) have found evi dence of an augmented frequency of cancer of the lung and pleura in a group of 288 persons, previously compensated for asbestosis arising from all occupations, who died between 1943 and 1967. In a subgroup of 32 miners exposed to chrysotile only, there was no augmentation of the rate of cancer of lung and pleura. Al though these studies suggest that chrysotile has little or no carcinogenic influence, more ex tensive and refined epidemiologic data are needed before reaching that conclusion. The possibility that the carcinogenic role of asbestos is solely that of a cocarcinogen is very strong. The data of Selikoff and associates (25) are especially pertinent in this regard, in that not a single bronchogenic cancer has been found in an insulation worker who was a noncigarette smoker, even though the exposure to asbestos experienced by the nonsmokers was the same as that of those who smoked and did develop lung cancer. 4Webster, I.: Personal communication. The considerable variation in the lung cancer incidence between populations of dif fering types of employment may be solely related to dosage, but it may also be the result of differing cocarcinogens. Gross and associates (26) produced a higher than anticipated fre quency of pulmonary cancer in rats exposed to chrysotile. They attributed this variance, from the experience of others, to be related to con tamination of the chrysotile fibers by nickel, cobalt, and chromium caused by the wear of the metal components of the mill used in pre paring the fiber for administration to their ani mals. Cralley and associates (19, 20) showed sub stantial amounts of these trace metals in the asbestos fibers used commercially. Miller and as sociates (27) have shown that benzo (a) pyrene plus asbestos augments the yield of pulmo nary tumors produced by benzo (a) pyrene alone. Harington and associates (28) raised the possibility that adsorbed hydrocarbons occur ring natively or picked up in storage and handling may play a role in cocarcinogenesis. As reviewed in 1969, the role of asbestos in augmenting the incidence of bronchogenic can cer appears to be dose-related, may be dependent upon the specific category of fiber, especially in relation to the degree of effect, and appears to be that of a cocarcinogen. Mesothelioma: Subsequent to the earlier re ports linking occupational exposure to asbestos and bronchogenic cancer, there were several suggestions that tumors of the peritoneal and pleural mesothelium might be similarly linked. Interest in this phenomenon remained dormant, however, until Wagner (29), in 1959, reported 20 eases of pleural mesothelioma associated with the Northwest Cape region of South Africa. He suggested that these were related to exposure to crocidolite asbestos because 14 of the persons were born or had spent their early youth near Kuruman, where crocidolite production is one of the major industries. This observation prompted an intensive search for all mesothe liomas in South Africa. Gilson (30) plotted the number and distribution of the South African cases up to 1962 and demonstrated a striking concentration of cases in the Northwest Cape. Although almost none was found to occur elsewhere in South Africa, the inference that the concentration of mesotheliomas coincided with the sole source of crocidolite in South Africa would not be warranted. A substantial quantity of crocidoln many yeareastern Tr.i: site and chr; Investig.it have examin and the tre< lions oecup.. the result tii jjosure to a inesotheiiom. cases outsidi raiding are ; the United Ithe U .t. In mesothelioma anthophvllite <--*), and fc where the thoroughly ii dom, the as-t oi insulation v lacturing fact non.-lnp has insulation wor viith textile in cent study of o Canada will In ruo.-t of Urn been raise at risk with r 1 >und ow'-.de ; /.ice of work. "I'erulation by ten has been *Jcii by lay wri ave further c 'matter for tho <*n .as well as i employees. t '`''it mesotho H iO tf complete < per Among t ih> relationship ^norns of the ' 'wing lV re is a hv. ! " regarding i ' f tlir ih igno-is only i< the hwtologic crir " noet'-snv f '-^her the tun >~ii48V- aA'jifc,'---fn`fiui-* in the lung ations of diflay be solely >be the result and associates icipated tre ats exposed to ,-ariance, from elated to Con ors by nickel, the wear of 1 used in prei to their anii) showed sub metals in the Miller and aszo (a) pyrene d of pulmoi (a) pyrene 23) raised the irbons occur- storage and cinogenesis. if asbestos in ihogenic canbe mdent esp^ially in d appears to le earlier re e to asbestos were several iritoneal and ilarly linked, red dormant, >59, reported sociatpd with h Africa. He i exposure to the persons youth near ction is one observation all mesothe- plotted the >uth African d a striking invest Cape, d to occur nee that the ncided with outh Africa ial intity ASBESTOS AND HEALTH IN 1969 471 of crocidolite has been produced for a period of It is apparent that the overwhelming number of many years, hundreds of miles away in the cases thus far being related to asbestos are eastern Transvaal, the same area m which amo diagnosed on the basis of biopsy alone. Further site and chrysotile asbestos are produced (31). study will be needed to demonstrate whether Investigators in other parts of the world mesothelioma is being over or under diagnosed. have examined the distribution of mesotheliomas It one accepts that some kind of direct or and the frequency of mesothelioma m popula indirect relationship between asbestos and tions occupationally exposed to asbestos, with mesothelioma exists, does it involve a specific the result that a strong relationship between ex variety of fiber'/ The data from the U.S. and posure to asbestos hber and the presence of United Kingdom does not lend itself to resolving mesothelioma has been indicated. Most of the this question because chrysotile, amosite, and cases outside South Africa, where mining and crocidolite are mvoived in tiie insulation workers' milling are implicated, have been reported in exposure, and chrysotile plus crocidolite in that the United Kingdom and, to a lesser degree, m of the textile manulacturmg employees. If one the U.S. In spite of a thorough search, no examines the mining and milling exposures to mesotheliomas have been found associated with the specific variety of hber, interesting facts anthophyllite asbestos production in Finland emerge. Kiviluoto and Meurman (22) did not (22), and few are reported in France (32), find a single mesothelioma in a large popula where the subject has probably not been tion of miners and mill workers exposed only to thoroughly investigated. In the United King anthophyllite. This group worked for three dom, the association has been with populations months or more between the period of 1935 of insulation workers and asbestos textile manu and 1967. Although others have stressed the facturing factories (33). In the U.S., the rela long period of time required for mesothelioma tionship has been shown predominantly with development, one would think that if anthophyl insulation workers (16) and, to a lesser degree, lite by itself is implicated, at least one case with textile manufacturing employees (15). Re would have been found by now in a setting cent study of the distribution of mesotheliomas known to cause asbestosis and a somewhat aug in Canada will be commented upon later. mented frequency of bronchogenic cancer. In a In most of the studies to date, the question study of the distribution of mesotheliomas in has been raised as to whether the population Canada, McDonald and co-workers (35) were at risk with respect to mesothelioma is to be unable to show excess frequency in the geo found outside as well as inside the factory or graphic area where chrysotile, but no other place of work. There has been a plethora of variety of asbestos, is produced. speculation by students of the problem that The South African distribution of mesothe often has been accepted as fact or interpreted as liomas is unusually interesting. Webster (36) such by lay writers. These dramatic speculations reports that before the end of 1968, 179 cases have further compounded an already difficult of mesothelioma were agreed upon as meeting matter for those responsible for public protec acceptable criteria. Of these, the history of ex tion as well as those responsible for the health posure was known in 148 patients, and in 24 of employees. Controversial or paradoxic issues there was no asbestos exposure. Fifty-one pa about mesothelioma and asbestos deserve a tients had been exposed during the mining and more complete discussion than is possible in this milling of crocidolite in the Northwest Cape paper. Among the controversial features about only. An additional 52 patients with mesothe the relationship of asbestos exposure to meso lioma, not exposed occupationally, were as thelioma of the pleura and peritoneum are the sociated in some way with residence in the following. Northwest Cape. Sluis-Cremmer (31) has in There is a lively controversy among patholo dicated that about 20 per cent of all crocidolite gists regarding the requirements for establish production in South Africa actually comes from ing the diagnosis of primary mesothelioma (34). mines located in the Transvaal, a few hundred Not only is there a question with respect to miles from the Northwest Cape. He also indi the histologic criteria, but even more important, cated that although the exposure may have been the necessity for establishing by autopsy somewhat less intense in these mines than in whether the tumor is primary or secondary. those of the Northwest Cape, it nevertheless was f rl r Y i p u u V r r * i V ,,'A * - ' ..I--: ' .. Jaz& lM ii*. . Jt S k'tt'iW '* lfcfy 472 GEORGE W. WRIGHT high. The writer's inquiries confirm this and The question of whether there is a tolerable Kingdom, indicate further that the mines of the Trans exposure or threshold limit value for asbestos thelionu h vaal have been in operation for as many years without contracting an enhanced risk of de past four ' as those in the Northwest Cape. The mechanism veloping mesothelioma has been raised by the have been for obtaining data regarding mesothelioma finding of what, on first inquiry, seemed to be had a kim in the Transvaal crocidolite area is identical minor exposures to the fiber in nonoccupational (33). If or to that for the Northwest Cape. Because not a settings as a background for some of the cases cases abou single case of mesothelioma has been discovered of mesothelioma reported in South Africa (36) the innubi- from the crocidolite mines or surrounding com and the United Kingdom (33). Although origi discover.il >: munities of the Transvaal, although 51 cases nally it had been thought that there were many a mesotlu a have come from the crocidolite mines and 52 such examples of mesothelioma developing out This nun:! i additional cases from the neighboring commu side an occupation or occupation-associated en of the ndu! nity in the Northwest Cape producing exactly vironment, better and more complete exposure were gitani the same kind of fiber, the contention that histories reduced this proportion greatly. At tertain th>. crocidolite per se causes mesothelioma becomes present, 80 per cent or more of the mesothe may be m difficult to accept. Sluis-Cremmer (31) pointed liomas thus studied in the United Kingdom fashion by out this paradox in 1964. Webster (36), in his and South Africa have been shown to have an carcinogenic current report on asbestos exposures in South occupational or paraoccupational association If one pi Africa, likewise calls attention to this disparity. with asbestos fiber. The level of this exposure sized fiber.-: It is of equal interest that only 3 cases of is substantial. Most cases occurring outside breathed In mesothelioma have been reported as originat actual "on the job occupational exposure" occur rare occorre ing from the Transvaal, these being from the through an exposed worker living on the same occupation amosite asbestos mines (36). No cases of premises, who brings fiber into the home on his tolerable lev mesothelioma have been reported from the clothing, or through contamination of the does not cm chrysotile mines of the Transvaal. On the basis environment surrounding an industrial opera of mesotlu-!; of what is known about the number of tion which has cast airborne fiber into the (13) and M< persons employed, the intensity and duration of atmosphere for year- and thus exposed persons indicate th.u exposure, plus lapse time, one would expect living or working in such a neighborhood. This to asbestos far more than 3 cases of mesothelioma if was especially exemplified in the Northwest dence of an amosite had the same potential as the factor Cape region of South Africa where roads were mesothelioma causing mesotheliomas in the Northwest Cape. made of asbestos-bearing waste rock, where is substair.: d The dosage and particle size have not been women were employed in hand cobbing or in concept that sufficiently different in the Northwest Cape gleaning asbestos fiber from the waste heaps, eral public 1 and Transvaal to explain the striking absence and where the mill disseminated blue fiber quite the past. or minimal occurrence of mesotheliomas in widely around its location. There is reason to Ferruginosi the Transvaal. believe that these various types of exposure foregoing co The discovery of such a striking concentra have been substantial in the population thus ments ha\e c tion of mesotheliomas in the Northwest Cape involved during the past 40 years. that an epul- suggests the need for a thorough study of the With respect to neighborhood or paraoccupa among the i differences between this region and other areas tional exposure to asbestos in the U.S., it is (38). This ,.p of South Africa in terms of possible tiologie of interest that Borrow and co-workers (37) of Thomson . factors. That something other than, or in ad called attention to the fact that none of their several other-, dition to, asbestos plays a role in mesothelioma series of mesothelioma, gleaned from a com similar to a-1 formation seems inescapable. The geology and munity medical practice, fell into this cate persons knowi climate of the Northwest Cape differs con gory of exposure. asbestos fibrr- siderably from that of the Transvaal. Trace Is it reasonable to believe that the cases of of the adult c metals, chemicals, or oils adsorbed onto asbes mesothelioma in which no occupational or para tion of lung t: tos may be factors. If crocidolite is impli occupational asbestos exposure can be dis such tissue. 1 i cated, it is likely to be in the role of a co closed, amounting to less than 20 per cent of bodies in the i carcinogen, some additional agent providing the those reported from the United Kingdom and ently depend- difference between the experience of the North South Africa, in fact represent a reaction to examined and west Cape and the Transvaal. Much more study the casual exposures which might be experi search is mad- needs to be made of this aspect. enced by the public at large? In the United i I (40) report :! ,,,i i ^ ' v.uSSi: ASBESTOS AND HEALTH IN 1969 473 is a tolerable > Kingdom, where an intensive search for meso cent of the population exhibited these bodies. e for asbestos ] thelioma has been pursued actively during the These structures have been assumed by many to d risk of de- , raised by the , past four years, fewer than 100 cases thus far represent coated asbestos fibers and, therefore, have been discovered in persons who have not to indicate an exposure to the inhalation of as seemed to be ; had a known substantial exposure to asbestos bestos fiber, hence a higher risk of developing ^occupational ; (33). If one adds to this a portion of the 132 mesothelioma. Several facts militate against ie of the cases j cases about which there was no information, this conclusion. h Africa (36) j the number of persons who have not had a The coated fibers found in the lungs of the dthough origi- ? discoverable substantial exposure, but in whom public have not been proved to be asbestos re were many J a mesothelioma has developed, is less than 200. fibers. When they are found in persons who eveloping out- ` This number is such a minuscule proportion have experienced a heavy exposure to the in -associated en- ; of the adult population from which the cases halation of asbestos fiber, it is reasonable to nlete exposure s were gleaned that it becomes difficult to en assume that the bulk of these bodies do a greatly. At j tertain the view that the asbestos fibers that represent asbestos fiber. It has been shown, the mesothe- may be in the air and respired in a casual however, that other materials which are ted Kingdom n to have an d association this exposure rring outside posure" occur ; i ; i j fashion by the public at large pose a genuine carcinogenic threat. If one postulates that there are respirable sized fibers of asbestos in the ambient air breathed by the general public, the strikingly rare occurrence of mesothelioma not related to fibrous in nature will produce bodies of an identical appearance (41). Cralley and as sociates (42) have listed 20 mineral materials that are fibrous in nature and that may be widely disseminated in the environment of the : on the same f occupation strongly suggests that there is a general public. Because of the numerous other e home on his i tolerable level of airborne asbestos fiber which types of fibers that may, and almost cer ition of the does not cause an undue risk of development tainly do, gain access to human lungs where nstrial opera- of mesothelioma. The findings of Newhouse they become coated with an iron-protein com ber :nto the j (13) and McDonald and associates (35), which plex, Gross and co-workers (43) suggested the po. persons indicate that a genuine occupational exposure term ferruginous bodies for these structures borhood. This , to asbestos has been tolerated without evi and suggested that they be called asbestos le Northwest j dence of an increased risk of developing a bodies only when it is known with certainty, re roads were . mesothelioma, suggest that the tolerable level or can be presumed on the basis of known rock, where | is substantial. The evidence strongly favors the exposure, that the central fiber of the body is obbing or in waste heaps, ue fiber quite is reason to of exposure oulation thus j i [ j paraoccupaie U.S., it is workers (37) lone of their rom a com o this cate- the cases of onal or para can be dis per cent of concept that the casual exposure of the gen eral public has not exceeded such a level in the past. Ferruginous (asbestos) bodies. In spite of the foregoing considerations, additional develop ments have caused some investigators to suggest that an epidemic of mesotheliomas will occur among the general public in the near future (38). This apprehension is based on the finding of Thomson and associates (39), confirmed by several others, that structures identified as being similar to asbestos bodies (commonly seen in persons known to have an intensive exposure to asbestos fibers) are found in 25 per cent or more of the adult general public by direct examina tion of lung tissue or of the juices pressed from such tissue. The frequency of occurrence of these bodies in the lungs of the general public appar in fact asbestos. This would appear to be a far more accurate designation and scientific atti tude than to insist on calling all of these bodies asbestos bodies whether or not they are known to be such. The literature concerning ferruginous bodies has become quite large, and sweeping infer ences from their presence in the general pop ulation have been made (38, 44). Without attention to the necessary quantitative and qual itative factors, it has been predicted that the experience of the general public with respect to mesothelioma will parallel that which has thus far been disclosed in certain very specific occupational and paraoccupational settings. A number of facts indicate a great need for cau tion before arriving at such a serious con kingdom and ently depends upon the volume of lung tissue clusion. To transfer the experience of a specific reaction to examined and the intensity with which the occupational or paraoccupational population to t be experi- search is made, because Utidjian and co-workers the general public requires evidence that the i the United (40) report that in their series almost 100 per exposure of the public does, in fact, corre- :H St h t. % KaSj^ 474 GEORGE W. WEIGHT spond to those populations in which an in creased risk of mesothelioma is said to exist. This is especially true now that it has been demonstrated that there are some occupational populations in which the exposure to asbestos fiber exceeds many fold that of the general public and in which no evidence of an unusual mesothelioma risk was found (13, 22, 35). What is the present situation in this regard ? As indicated in foregoing discussions, con clusions with regard to the relationship be tween mesothelioma and asbestos fiber per se, even in an occupational setting, are rather un certain at this time. The roles of types of fiber, cocarcinogenesis, and dosage are so far from being clear in these special occupational set tings as to give little assurance that they can be transferred in any meaningful way to the nonoccupational related or general public popu lations. Although a scant number of ferruginous bodies has been demonstrated in lungs from the general public, there has been no demon stration that these are in fact the result of exposure to asbestos fiber rather than to one or more of the many other materials known to be capable of producing ferruginous bodies. At this time, the determination of whether the fibrous core of a ferruginous body is in fact asbestos is extraordinarily difficult and quite beyond the means of other than the most sophisticated laboratories. In spite of this, the necessary investigation must be done before the contention that all ferruginous bodies in the general public are in fact asbestos fibers can be accepted. Quantitative estimates indicate that the number of ferruginous bodies found in the lungs of the general public is a small fraction of the number found in the lungs of those who had been occupationally exposed. If one accepts the contention that ferruginous bodies reflect asbestos exposure, one must conclude that the general public has had far less ex posure than those persons in occupations us ing asbestos fiber. That some persons with known occupational exposure to asbestos fiber appear to have but few ferruginous bodies complicates an interpretation of quantitative measurement of ferruginous bodies. It is clear that much more comprehensive and reliable data with regard to the dynamics and the quantitative and qualitative aspects of fer ruginous bodies is necessary before any mean ingful interpretation of their importance for the general public can be made. The finding of ferruginous bodies in a large proportion of the general population has led to the contention that the augmented use of asbestos in the manufacture of products has greatly increased the degree to which the gen eral public has been exposed to this fiber. This assumption has been based upon the simple statistic of asbestos consumption, with no attention being paid to how the fiber is used nor the degree to which its ultimate fabricated form would lend itself to dissemi nation of fiber among the public (30). Al though it is possible that augmented consump tion of asbestos fiber led to a greater output of these fibers from factories into the air sur rounding the factory, this does not constitute a generalized public environmental exposure. Tabershaw (45) has pointed out that asbestos is used for the most part in fabrication of materials that are unlikely to become air borne. It is not widely appreciated that the bulk of the products using asbestos actually bind the fiber firmly in the product, and there is subsequently very little opportunity for re lease of this fiber except by slow wear of the products. The estimated consumption of asbestos fiber in the U.S. has increased from 125,000 short tons m 1918 to 720,000 in 1965; most of the increase occurred after 1940.5 Once the fiber, in the form of a product, is put into place, it is not released except by gradual wear, which in most examples is minimal. During factory processing, the public at large is not exposed. During the use of certain products, such as insulation removal and application, fibers are released and those in the immediate vicinity, workmen and public, may be exposed. This category of product can be thought of as having fibers that are "loosely bound," in con trast to such products as asbestos cement or floor tile which actually incorporate the fibers and bind them very tightly. The quantity of asbestos fiber used for "loosely bound" products, including insulation (figure 1), has increased from 39,000 only to 55,000 short tons between 1920 and 1965." The commercial grade of fiber indicates the kind of products in which it will be used. "Pundsack, F.: Personal communication. <.00 350 300 V50 - o 5 *ool o 150 - 100 - 0 i 0_ 1 Fio. 1. Aihoun aecoiding to ihe l t bound" products f installation, or rer ` That most of the au ; tion of chrysotile has 1 7 (especially 7) is sh * 7 goes predominantly floor tile which usual 25 years or more bei result of decoration i wear. The bulk of gr: 1 asbestos cement prod' cement pipe, in whiei ; is indefinite--systems m 30 years old. Air cont;. ! from this source. Alt he - weathering of asbestos siding, the rate of wen readily be seen that a' an augmented utilizatie ' largest fraction of it i bound products desurm The wear from the-c p | than the total product terial is discarded. . Asbestos forms an os jt materials. Concern has i any meanrtance for in a large n has led ed use of ducts has h the genthis fiber, upon the 'tion, with le fiber is 5 ultimate o dissemi- (30). Alconsumpcer output le air sur.mstitute a exposure, it asbestos cation of come air[ that the s actually and there ty re ear of the estos fiber ,000 short ost of the the fiber, nto place, ear, which lg factory cposed. s, such as fibers are e vicinity, )sed. This ;ht of as I," in con cernent or the fibers uantity of ' products, increased is between iicates the be used, on. ASBESTOS AND HEALTH IN 1969 U. S. A. IMPORTS CHRYSOTILE ONLY 475 Fio. 1. Amount of chrysotile asbestos (short tons) used in the U. S. during 1930 to 1965, according to the grade of fiber. Longest fibers are grade 3 and shortest are grade 7. "Loosely bound" products include insulation and other materials that may release fibers during use, installation, or removal. That most of the augmentation of consump tion of chrysotile has been in grades 4, 6, and 7 (especially 7) is shown in figure 1. Grade 7 goes predominantly into asphalt and vinyl floor tile which usually has a life of 20 to 25 years or more before it is changed, as a result of decoration alterations rather than wear. The bulk of grades 4 and 6 goes into asbestos cement products, especially asbestos cement pipe, in which the replacement time is indefinite--systems now in use are more than 30 years old. Air contamination does not occur from this source. Although there may be some weathering of asbestos cement shingles and siding, the rate of wear is very slow. It can readily be seen that although there has been an augmented utilization of asbestos fiber, the largest fraction of it has gone into strongly bound products designed to last many years. The wear from these products is also far less than the total product by the time the ma terial is discarded. Asbestos forms an essential part of friction materials. Concern has been expressed that the public is exposed to large quantities of asbestos fiber liberated by the wear of automobile brake linings. This is unwarranted. The amount of asbestos fiber used in friction material in the U.S. was estimated at 33,000 tons, less than 5 per cent of the total in 1965." Studies of the ma terial released during the use of brakes (46) demonstrated that the high heat of friction destroys the asbestos converting it to an amorphous material no longer having the char acteristics of asbestos. Of the total materials removed from brake linings during their use, less than 5 per cent appears as actual asbestos. The amount of asbestos fiber released by normal friction material wear must be small indeed. The fibers that might be released from all kinds of wear either become intimately bound with the soil or are captured in either rain water or in water used for cleansing. Ultimately the fibers are distributed predominantly where water is distributed. A study of river water has shown that asbestos fiber is almost universally present although in quite small amounts. How "iftMttektetra;; i 476 GEORGE W. WRIGHT TABLE 1 A mount o r C ommercial T alc U sed for Various P roducts in th e U.S. (Sh o rt T ons in 1967) Total U.S. consumption Ceramics Paint Roofing Insecticides Paper Refractories Rubber Toilet preparations Other 826,000 220,000 153,000 72,000 69,000 45,000 41,000 31,000 28,000 167,000 Total U.S. consumption of asbestos in 1965 was 720,000 short tons. much of this comes from wear of products and how much from leaching of soil is of course not determined. The concept that asbestos is indestructible is fallacious, and the belief that it accumulates on the surface of streets and other places seems ill-founded. The possibility that sources of fiber other than commercial asbestos may lead to ferrugi nous bodies must be considered. Talc is a form of magnesium silicate that exists in sev eral forms, has large industrial use, and com monly is contaminated by fibrous substances such as tremolite and even chrysotile. It should be noted that talc production has been shown to cause pulmonary fibrosis and possibly in fluence the development of bronchogenic can cer (47). As shown in table 1, the consumption of commercial talc in the U.S. exceeds that for asbestos. Attention to some of the products made suggests that the opportunities for air borne talc dissemination may have been aug mented to an even greater degree than has asbestos. Cralley and associates (48), in an assessment of 22 cosmetic talcum powders purchased in the U.S., found that an average of 20 per cent of the particles were fibers. These fibers are fully capable of producing ferruginous bodies in the experimental animal. It is of interest to note that the amount of commercial talc that ultimately finds its way into toilet preparations is far in excess of the amount of asbestos used in the manufacture of insulation materials. Insecticide preparations consume a larger tonnage than all of the un bound kinds of asbestos fiber put together. Rubber, which utilizes a large amount of com mercial talc, may contribute to the discharge of fibers in the general environment as a result of wear. It is obvious from these data that commercial talc provides a potent source at least equivalent to that of asbestos for supply ing respirable-sized fibers that could produce ferruginous bodies. It is difficult to conceive of a better way of having fibers inhaled than the use of cosmetic talcum powders. In this re gard, it is of interest that Avril and Champeix (49) found no ferruginous bodies in 138 autopsies in France. It is claimed that the cosmetic talcum in France has no fibers." The extent to which other mineral or vegetable fibers known to be present in the environ ment of the general public may contribute to the production of ferruginous bodies is as yet unknown. Data have been reported recently by Selikoff and Hammond (50) showing that the frequency of occurrence of ferruginous bodies is essen tially the same in lungs obtained by autopsy in 1934 as in 1967, a finding difficult to reconcile with the contention that the augmented use of asbestos during the past 35 years has greatly enhanced the exposure of the general public to asbestos fiber. It also raises the question of whether the fibers in these ferruginous bodies are in fact asbestos. A similar study in Great Britain failed to demonstrate any ferrugi nous bodies in lung samples obtained at ne cropsy in 1936 or in lung samples from fe males autopsied in 1946 (51). Although they may have been fewer than now, there surely must have been potent sources for the dissemi nation of both talc and asbestos in Great Britain before 1936 and 1946. The previous findings provide little or no evidence to suggest that an epidemic of mesothelioma among the public at large is to be expected. In a more positive way, the data from South Africa indicate that during the past five or six years the number of new cases of mesothelioma have been rather constant at approximately 20 per year, and in Great Britain (33)* only a moderate increase has been shown. Although the study of ferruginous bodies is of interest, the necessity for the central core to be identified and for quantitative data to be obtained in order that more meaningful conclusions be reached about their import ' Avril, J.: Personal communication. sugges dim mi more in the ful av. direct fiber j enviroi with r< and g. would inform, posure, ferrugii history to the : air wo what t) ent. Plcur town rd result e the firs of asbe to difn. been a t pleura < this thi pearanc* calcified from nn irregulai plaques matter time. U often ab diffuse j longed i may be no diffu pleural common posed oc or near i produeeu other ca cation, a ascribe asbestos asbestos siderable there is result i that rce at upplyroduce ive of m the is rempeix i 138 t the The etable vironribute is as elikoff uency essenasy in oncile rse of reatly public on of iod; Gn. rrugit nen fe- they mrely isemiGreat >r no c of is to data : past es of \t at Great has jodies ;ntral data ngful nport ASBESTOS AND HEALTH IN 1969 477 suggests that this is an area of study with diminishing returns. A direct approach to the more easily identifiable naked fibers contained in the lung would appear to be a more fruit ful avenue of search. Still better would be a direct approach to the types and amounts of fiber present in the ambient air of the various environmental locations that are of interest with respect to occupational, paraoccupational, and general public exposure. Although this would pose the disadvantage of not giving information with regard to long-term past ex posure, there is equally no guarantee that ferruginous bodies truly represent the complete history of past exposure. The direct approach to the study of fiber populations in the ambient air would have the advantage of telling us what the conditions are for the public at pres ent. Pleural plaques: Attention has been directed toward another phenomenon said to be the result of past exposure to asbestos fiber. Since the first recognition that prolonged inhalation of asbestos fibers might in some persons lead to diffuse pulmonary fibrosis, clinicians have been aware that areas of thickening of the pleura occur in some such persons. At times, this thickening is localized leading to the ap pearance of plaques, some of which may be calcified. The pleura effects range all the way from minimal findings to extensive and bizarre, irregularly shaped, calcific masses. Pleural plaques with or without calcification are a matter of considerable interest at the present time. Unexpectedly, these manifestations are often absent in persons who have well-developed diffuse pulmonary fibrosis resulting from pro longed exposure to asbestos fiber, and they may be very extensive in persons with little or no diffuse fibrosis. In fact, rather extensive pleural plaques have been reported as being common in large populations not directly ex posed occupationally to asbestos, but living in or near the region where asbestos fiber is being produced or used (52). There are, of course, other causes for pleural plaques and calcifi cation, and, in some instances, it is unwise to ascribe these findings to the inhalation of asbestos fiber. In a geographic area where asbestos fiber is known to be present in con siderable concentration in the ambient air, there is every reason to believe that from an epidemiologic point of view it is proper to consider these findings as evidence of asbestos exposure. Long-term implications of pleural plaques are a matter of interest. In general, unless the thickening of the pleura is extensive, the ef fects of this patchy thickening on various as pects of pulmonary function are minimal or absent.' There is no evidence that the presence of pleural plaques connotes anything with re spect to the ultimate development of mesothe lioma. In fact, two of the geographic areas in which the largest concentrations of pleural plaques have been reported, Finland (52) and eastern Quebec Province,' do not have a demonstrated excessive frequency of mesothe lioma. To use the presence of pleural plaques as a marker of previous asbestos exposure is of limited value, in view of the fact that other causes lead to this condition and especially in view of the fact that the absence of plaques in no way connotes the absence of absestos ex posure. *** The relationship between asbestos and health of humans, as reviewable in 1969, indicates that serious exposures to asbestos fiber can occur in certain occupational and immediately ad jacent environments. Fortunately, the con centration of asbestos fibers in these settings can be controlled. The environment of the in sulation workers is more difficult to control than the more fixed and permanent environ ment of the factory and associated neighbor hood. An approximation of the concentration of respirable-sized asbestos fiber that can be tolerated without the risk of pulmonary fibrosis has been achieved. There is reason to believe that this concentration will also minimize the risk of pulmonary malignancy including meso thelioma. Because of the long time lapse as sociated with the development of malignancy, longer periods of observation are desirable for a final decision on this point. There is reason to believe that the occupational use of asbestos fiber can achieve the same degree of safety as the use of explosives, radiation, and beryllium, although extensive alterations may be required in the control of production and manufacturing, 'Becklake, M.: Personal communication. ' Cartier, P.: Personal communication. ft' 478 GEORGE W. WRIGHT the containment of asbestos fiber so that none (13) Newhouse, M. L.: The mortality of asbestos escapes to the outside, and the proper disposal factory workers, Proceedings of the Inter of solid wastes containing the fiber. The risk to the general public posed by the mostly intermittent exposure to the low con national Conference on Pneumoconiosis, Department of Mines, Republic of South Africa, 1969, to be published. (14) Enterline, P. E. and Kendrick, M. A.: centrations of asbestos likely to be present in Asbestos dust exposures at various levels the ambient air has been exaggerated beyond the limits imposed by known facts. Research to develop the necessary additional information upon which appropriate and realistic measures and mortality, Arch. Environ. Health, (Chicago) 1967,15, 181. (15) Mancuso, T. F., and El-Attar, A. E.: Car cinogenic risk and duration of employment among asbestos workers, Proceedings of the for safe use of asbestos fiber can be taken 2nd International Conference on the Bio should be the goal in the next few years. logical Effects of Asbestos, 1968, in press. (16) Selikoff, I. J., Hammond, E. 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