Document 4Q4K8RyBn31mMRqK9xKEzLKqa

\W'/ \ ? American Academy of Occupational Medicine a 285 PLAINTIFFS EXHIBIT ___ UC-83 Asbestos as a Hazard to Health Fact and Speculation ir. Clark Cooper, MD, Berkeley, Calif . A RESURGENCE of interest in the as- bestosis. No one disputes a cause-and-effect bestos minerals as environmental hazards to relationship here; but we are still deficient health has arisen because of increasing in our knowledge"of pathogenesis. "'N world production of asbestos, successive in- Are alWorms of asbestos equally hazard- dications of associations between asbestos ous?'The evidence is against this. Chryso and pulmonary fibrosis and various malig tile disappears more readily from the lungs nancies, and, more recently, the demonstra ~than other forms and in animals sepms to be I tion of asbestos or asbestoid bodies in pre less fibrogenic. The prominence of pleural1 sumably nonexposed populations. \ calcification varies from area to aretu ahd The major asbestos minerals of commerce ''type to type. For example, inFjuolarid, Rau- are chrysotile, croddolite, amosite, and an- nio>--Jiaq recvnt|v -axpnrt&C a review of thophyllite, with tremolite and actinolite 600,000 chest x-ray films which show that being of considerably less importance. The in communes where anthophyllite mines are properties of these various fibrous minerals located, up to 9% of films showed pleural have led to an extraordinary variety of uses, calcifications, whereas in other parts of East so that world production has increased from Finland not bordering on producing com a few thousand tons in 1900, to 1.3 million munes the prevalence was only 0.5% per tons in 1950, to over 3.5 million tons in 1965. thousand. Nothing comparable to this has Over 90% of this is chrysotile. The United been reported in other asbestos-mining areas. States uses about one fourth of world pro A second question regarding asbestosis duction, practically all imported from Cana relates to its prevention by industrial hy da or Africa.1 giene. Is it true that all that is needed is the application of currently recommended Asbestosis standards for dust control? Most people who have looked into the basis for the The first facts to be discussed will be present threshold limit value of 5 million those relating to asbestos pneumoconiosis, particles per cubic foot for asbestos, which the disease that has come to be known as as- has been recommended by the American Submitted for publication Juno 19, 1967; accepted June 28. From the School of Public Health, University of California, Berkeley. Read before the 19th annual meeting of the Amer ican Academy of Occupational Medicine; San Fran cisco, Feb 8, 1967. Reprint requests to School of Public Health. Earl Warren Hall, University of California, Berkeley 94720 (Dr. Cooper). Conference of Governmental Industrial Hy gienists (ACGIH) since 1946, realize that it rests on shakier evidence than most. Midget impinger sampling used in determining dust concentrations include all dusts; and the asbestos-containing dust that is counted is mainly grains, although, rarely, some fibers are included. A large proportion of asbestos Arch Environ Health--Vol 15, Sept 1967 286 A S'RESTOSIS--COOPER fibers have diameters below the resolving power of the light microscope and are not -- counted at all. Nevertheless, most industrial hygienists have felt that the impinger count is a good indirect measure of dust control and that dust counts averaging 5 million particles per cubic foot (mppcf) should con* trol asbestosis. Evidence is beginning to develop that this is not true. In 1965, Wells3 ^ reported briefly on his observations over 30 years in asbestos textiles. His view was that multiplying average counts by years of ex posure provided a good rough guide and that after 50- to 60-mppcf years workers began to show evidence of asbestosis. At the threshold limit value (TVL), this would be reached in 10 to 12 years. In 1966, Ferris examined insulating workers in a New England ship^ yard that had been surveyed by Fleischer et al4 20 years earlier. His preliminary results indicate that conditions and counts now ap pear comparable to those of 20 years ago and average near 5 mppcf (B.G. Ferris, oral communication, Dec 8, 1966). Nevertheless, a large proportion of workers had radiographic asbestosis, which had begun to ap pear as early as 10 to 12 years before. Marr's counts3 in shipyards, in 1964, did not indi cate weighted averages above 5 mppcf; and current studies of insulating workers in San Francisco bear this out (J.L. Balzer and W.C. Cooper, unpublished data, 1967). Nev ertheless, asbestosis appears, which suggests that a time-weighted average of 5 mppcf may be too high. This is consistent with actual practices in the better controlled as bestos industries. Mitchell, reporting in 1961 on improved conditions in North Caro lina textile mills, cited counts ranging from 0.4 to 4.6 mppcf. English industries under Asbestos Industry Regulations have never operated with a numerical standard, instead depending upon enclosure, ventilation, and masks to keep exposures as near -zero as possible. There are numerous other questions that one can ask relative to asbestos pneumo coniosis. Have we been too complacent in assuming that the expectoration of large numbers of asbestos bodies is the expected response of an asbestos worker, or is this in the new employee really an indicator that we are tolerating too much exposure? I do not think we know the answer. There are also fundamental questions on pathogenesis, on the nature of the pulmonary vascular im pairment, and the factors determining sus ceptibility. Malignancies Asbestos would not be in the headlines if asbestosis, affecting a few hundred miners, millers, and insulating workers, were the only problem. It is the more recently demon strated association between asbestos and malignancies that has created an entirely new series of facts, fantasies, fallacies, and fancies. Let us first look at the evidence. That there is an increased incidence of lung cancer in many groups of workers ex posed to asbestos is a fact. The cumulative evidence from epidemiologic studies (Table 1) that began with Merewether's analysis7 of causes of death in certified cases of asbes tos in the United Kingdom from 1924 to 1947 is now overwhelming. The evidence is not convincing as to the relative importance of different types of asbestos. Chrysotile seems less certainly im plicated; and one looks forward with inter est to an up-dating of the experience of Que bec chrysotile miners who, several years ago, when analyzed by Braun and Truan11 ap peared to have no excess risk. It is of inter est that Jacob and" Anspach19 who a few years ago could demonstrate no increased risk in Dresden asbestos workers now find twice the expected number of cases of lung cancer in men and ten times the expected number in women. Their exposures were mixed, and we do not have the answer to whether the association is truly less for chrysotile than it is for crocidolite and amosite. The next question, and this will apply to other malignancies to be mentioned later, is whether or not asbestos minerals per se are carcinogenic. A promising area of current research is aimed at determining the role of the asbestos fibers and fibrils as carriers of trace metals or of carcinogenic chemicals, such as the polycyclic hydrocarbons, to vul nerable sites. The idea of a fibril that can migrate and then become a semipermanent implant is an intriguing one. This falls into the area of speculation, or fancy if you wish to call it that, but one that may prove pro ductive. Arch Environ Health--Veil IS, Sept 1967 M 7 92b ASBESTOSIS--COOPER 287 Table 1.--Epidemiologic Studies of Asbestos Exposures and Lung Cancer Place United Kingdom7 United Kingdom* United Kingdom' United Kingdom10 Quebec11 Pennsylvania12 New York & New Jersey12 California1' Population Studied Reported deaths Irom asbestos Cases of asbestosis in 1247 autopsies with pneumoconiosis Asbestos textile workers, dusty areas. 20 yrs or more exposure Reported deaths from asbestosis Chrysotile miners & mill workers, with over 5 yrs employment Workers in asbestos products plant, aged 25-64, employed as of 1938-39 Insulating workers, over 20 yrs since joining union Insulating workers mixed, 15yrs in trade, age 35-64 Nu. 235 121 113 365 5,958 1.495 632 529 Dresden12 United States1* United Kingdom17 All asbestos trades mixed exposures Asbestos textile workers, employed in 1948-51, age 15-64 Reported deaths from asbestosis 2,636 2,833 584 * Includes cases reported by Merewether 1949. t Includes cases reported by Merewether 1949 and 1955. Years Followed 1924*194 7 ~ ~ 1922-1953 1924-1955 1950-1955 1940-1960 No. With Lung Cancer 31/235 (13.1%) 17/121 (14.1%) 11/39 deaths 65/365* (17.8%) 9/187 deaths 19/186 deaths 1932-1962 1534-1957 to 1962 av. 7.1 yrs 1924-1963 1951-1963 1924-1963 45/255 deaths 10/41 deaths 34/150 deaths 24/285 ileaths 146/584t (25%) Comparison Groups Silicotics (1-32%) Silicotics (6.9%) " 0.8 expected 6+ expected 5.61 expected 6.6 expected 2.8 expected 11.9 expected 11.9 expected Within the past five years, there has been increasing evidence of an association be tween asbestos and diffuse pleural and peri toneal mesotheliomata. Since the first dem onstration of a major series of cases, that of Wagner, Sleggs, and Mardiand,18 there have been over 25 reports in the literature. In many of them there have been suggested associations with asbestos, either by occupa tional history or demonstration of asbestos bodies in lung tissue sections. Inasmuch as mesotheliomata were regarded as excessive ly rare tumors until recently, the occurrence of even two or three in a series of asbestos workers becomes statistically significant. Separating fact and fancy here becomes a bit more difficult. First, how accurate are our diagnoses of diffuse mesotheliomata? There is no question but that rigid criteria to exclude primary tumors elsewhere are necessary inasmuch as the histologic charac teristics of undifferentiated spreading tu mors of the pleura and peritoneum are not always distinctive. Close scrutiny of most series of diagnosed cases results in the exclu sion of many of them. Nevertheless, where rigid criteria have been applied, as in the cases studied by Hourihane,30 in 1964, in London Hospital, the association with asbes tos has been strengthened, not weakened. A second question regarding these tumors is whether or not theirjncidence in the popula tion as a whole is increasing. The impres sion one gets is that they are. Third, if there is an association, is it more evident with one form of asbestos than another? Here, there is no question but that crocidolite, and especially Cape blue crocidolite, is the type where evidence is strongest. In this country, reported series have involved mixed exposures, usually including amosite. Claims have been made that because amosite was not used in the United States to any extent before 1935 and since mesothelioma characteristically have very long latent peri ods from first exposure to diagnosis, we are either seeing responses to chrysotile or are seeing only the first cases in an epidemic of effects from amosite. That anthophyllite is not a problem in this respect is strongly sug gested by a recent report by Raunio2 in which the very high prevalences of pleural calcification in anthophyllite mining areas of Finland was not associated with any in creased frequency of cancer of the lung or of Arch Environ Health--Voi IS, Sept 1967 A 1792 6 288 ASRESTOSIS--COOPER malignant pleural or peritoneal tumors. We are left with a strong body of evidence that individuals with light, moderate, and heavy exposures to crocidolitc, amosite, or mix tures of amosite and chrysotile show tumors of a type that is much less common in the general population. Studies in animals in 1962 by Wagner-0 in Wales and in 1965 by Smith-1 and others in New Jersey have led to production of mesothelial tumors in hamsters in which various types of asbestos were introduced intropleurally. The difficulty in preventing cross contamination in laboratories has com plicated some of these animal studies, so that differences in response to different types of asbestos and co-factors remain un clear. Nevertheless, the carcinogenic poten tial of asbestos minerals appears to have been confirmed, although the role of go-fac tors has not been settled. Ferruginous Bodies The final question is, is it true that from a fourth to a half of the general population harbors asbestos fibers in its lungs? The ba sis for such a statement is the fact that a number of studies of routine consecutive au topsy specimens in recent years have dem onstrated "asbestos bodies," or as Gough22 would prefer to call them, "mineral-fibrebodies," or Gross, "ferruginous bodies." As far back as 1928, Stewart24 had shown that smears of the cut surface of the fresh lung at autopsy would reveal large numbers of as bestos bodies in the asbestotic. If anyone tried this in a supposedly unexposed popula tion before studies done in South Africa in the 1960's, it was not published. In 1963, Thomson et al25 showed 26.4% in 500 con secutive autopsies in Cape Town and later, in 1966,20 27.2% in 400 autopsies in Miami. These and other studies are summarized in Table 2. The facts that have emerged from these are as follows: 1. Morphologically and in staining prop erties, these meet all criteria for asbestos bodies. 2. In no studies, so far published, have there been__supporting data to indicate whether all, most, or some of the bodies were asbestos. 3. In most series, about 80% to 90% of Place Table 2.--Ferruginous Bodies in Human Lungs in Autopsy Series' Percent Positive Cape Town**Miami" Pittsburgh17 Johannesburg" Finland" Montreal*' San Franciscot 1963 1965 1965 1965 1966 1966 1966 26.4 27.2 41 39.2 57.6 48 42 Based on lung smears except series from Finland, where thick sections were examined. ? W. C. Cooper and I. R. Tabershaw, unpublished data, 1966. the positive reports were on the basis of rel atively few asbestos bodies per case. 4. In those with many bodies, there were often but not invariably occupational or res idential clues as to a source of asbestos and they were most commonly in males. 5. In none of the series, all small, where correlations were attempted with diagnosis, was there any apparent association with malignancies or other specific causes of death. 6. There is ample evidence in the litera ture that so-called "asbestos bodies can be found in workers with exposure" other than asbestos, eg, graphite workers, soft coal miners, diatomaceous eartlTworkers.^etc. 7. Ferruginous bodies can be produced experimentally in guinea pigs with other dusts. Presumably, they represent a nonspe cific response to any relatively insoluble fibrous material in the lungs. Speaking of this, Cooke31 said, ". . . there is no reason why any fine spicule of mineral should not have colloidal matter deposited around it and become moulded into a curious body. But as no other mineral dust is fibrous, this occurrence must be so rare as to be negligible from a diagnostic point of view." The question now, is Cooke's statement of 40 years ago true today? Or, are we adding fibers of many kinds to our environment, giving a confusing picture of our human samplers? If, as is probable, many of the bodies that are being seen are really asbestos minerals, there is need to determine their significance. It is unwarranted to draw the conclusion from what we now know that they necessari ly presage an epidemic of neoplasms. It is Arch Enuiron Health--Vol IS, Sept 2967 A 17927 ASBESTOSfS--COOPER 289 quite warranted to speculate on the matter, however. It is important not only to identify positively these ferruginous bodies but also to quantitate them in populations with known exposures to various fibrous miner als. If those with small or moderate numbers of asbestos bodies show no detectable in creased risk of disease, then one could feel more secure about those in whom the bodies are scant in number. It is also important to learn the sources of these fibrous minerals that are found in lungs. The view that asbestos minerals are indestructible is not quite true; this is a relative term only, and we cannot assume that the millions of tons used annually ac tually enter our physical environment for ever. Many are bound indefinitely into prod ucts that do not release them; those that are released are subject to the effects of heat, acids, and other insults to minerals. Nev ertheless, it is important to get a better idea of our asbestos balance, so to speak. Summary In summary, with the increasing use and indispensability of asbestos minerals, there has come realization of some very real haz ards that must be better defined and con trolled. Present standards for dust control do not appear adequate to prevent asbestosis over a working lifetime, and many seg ments of industry aggressively attacking the r problem have already been rising more rig orous standards. The associations between asbestos minerals and malignancies of the lungs, pleura, and peritoneum have become increasingly convincing. Current efforts must be directed toward better definition of the importance of type, size of fiber and the importance of co-factors. It has been sug gested that asbestos fibers act as carriers of carcinogenic metals or other substances to vulnerable sites. The demonstration of fer ruginous bodies in from one-quarter to onehalf of the lungs examined in consecutive autopsies in a number of cities around the world points to an urgent need for the posi tive identification of the mineral fibers that are responsible If they prove to be asbestos, we do not know what point on the dosage response curve is represented and conse quently are not now in a position to estimate their significance in terms of human health. Conclusions I have one final set of conclusions. I think you will notice that I have not conformed to the usual pattern of talks with titles such as the one I was assigned, lining up on the one hand a list of the things we really know and then decrying unwarranted and mischievous extrapolations. Actually, that could have been done here, as I do think misleading statements have Keen made with resoect-to asbestos. The more fundamental problem is one that is a major affliction of occupational health. We often try to emphasize that part of the challenge of the field is that it is at the forefront of medicine and technology, where environmental hazards can first be detected, in view of the relative levels of ex posure and the opportunities to study popu lations at risk. But when relationships are actually suspected and then gradually estab lished, very real and practical consequences become apparent. So the speculations, call them fancies if you.wiil, that are pirt of the normal process of developing new knowl edge in other fields become menacing and are misused and misunderstood. Polariza tion of views and severance of communica tion is the rule, not the exception. I think that this has been the case history of much occupational disease research in the United States, and I cannot say I know how it could be eliminated. I do believe, however, that scientific progress requires both fact and fancy. References X. May, T.: "Asbestos," in Mineral Facte and Probleme, US Department at the Interior Bulletin No. 630, 1965. 2. Raunio, V.: Occurrence of Unusual Pleural Calcification in Finland: Study on Atmospheric Pol lution Caused by Asbestos, Supplement 47 to vol 55, Ann Med Intern Fenniae, Helsinki, 1966. 3. Wells, J.: in discussion Hills, D.W.: Economics o{ Dust Control, Ann NY Acad Sci 132:335-336 (Dec 31) 1965. 4. Fleischer, W.E., et si: A Health Survey of Pipe-Covering Operations in Constructing Naval Vessels, J Industr Hyg Teat 28:9-16, 1946. 5. Marr, W.T.: Asbestos Exposure During Naval Vessel Overhaul, Amer Industr Hyg Assoc J 25:264268, 1964. 6. Mitchell, J.: Health Progress in an Asbestos Textile Works, Arch Environ Health 3:37-41,1961. Arch Environ Health--Vol 15, Sept 1967 A; 7928 290 ASBESTOSIS--COOPF.U 7. Merewether, E.K.A.: Annual Report of the Chief Inspector of Factories for the Year 1947. Lon- don: Her Majesty's Stationery Office, pp 79-87. 1949. 8. Gloyne, S.R: Pneumoconiosis: A Histological Survey of Necropsy Material in 120.1 Cases, I.ancrt 1:810-814 (April 14) 1951. 9. Doll, R: Mortality From Lung Cancer in As bestos Workers, Brit J Induetr Med 12:81-86. (April) 1955. 10. Memwether, E-R-A.: Annual Report of the Chief Intpeetor of Faetoriet for the Year 1.955, Inn- don: Her Majesty's Stationery Office, 1955, p 206. 11. Braun, D.C., and Truan, T.D.: An Epidemio logical Study of Lung Cancer in Asbestos Miners, Arch Induetr Health 17:634-653, 1958. 12. Mancuso, T.F., and Coulter, E.J.: Methodolo gy in Industrial Health Studies, Arch Environ Health 6:515-524, 1963. 13. Selikoff, U.; Churg, J.; and Hammond, E.C.: Asbestos Exposure and Neoplasia, JAMA 188:22-26, 1964. * 14. Dunn, J.E,, and Weir, J.M.: Cancer Experi ence of Several Occupational Groups Followed Pro spectively, Amer J Public Health 55:1367-1375, (Sept) 1965. 15. Jacob, G., and Anspach, M.: Pulmonary Neo plasia Among Dresden Asbestos Workers, Ann NY Acad Sci 132:536-548 (Dec 31) 1965. 16. Enterline, P.E.: Mortality Among Asbestos Products Workers in the United States, Ann NY Acad Sci 132:156-165, 1965. 17. Buchanan, W.D.: Asbestosis and Primary In- trathoracic Neoplasms, Ann NY Acad Sci 132:507- 518 (Dec 31) 1965. 18. Wagner, J.C.; Sleggs, C.A.; and Marchand. P.: Diffuse Pleural Mesothelioma and Asbestos Expo sure in the North-Western Cape Province, Brit J Induetr Med 17:260-271, 1960. 19. Hourihane, D.O.: The Pathology of Mesothe- iiomata and an Analysis of Their Association With Asbestos Exposure, Thorax 19:268-278, 1964. 20. Wagner, J.C.: Experimental Production of Mesothelinl Tumors of the Pleura by Implantation of Dusts in Laboratory Animals, Nature 196:180, 1962. 21. Smith, W.K., et nl: Mesotheliomas in Ham sters Following Intrtipleural Injection of Asbestos, J Mt Sinai Hasp 32:1-8, 1965. 22. Gough, J.: Differential Diagnosis in the Pa thology of Asbestosis. Ann NY Acad Sci 132:368- 372 (Dec 31) 1965. 23. Gross, I*.: Today's Pressing Question--How Safe is Urban Ambient Air? Arch Path 86:195 (Aug) 1966. 24. Stewart, MJ.: The Immediate Diagnosis of Pulmonary Asbestosis at Necropsy, Brit Med J 2:509, (Sept 15) 1928. 25. Thomson, J.G.: Kaschula, ROC.; and Mc Donald, RR: Asbestosis as a Modem Urban Haz ard. S Afr Med J 37:77-81. 1963. 26. Thomson, J.G., and Graves, W.M. Jr.: Asbes tos as an Urban Air Contaminant, Arch Path 81:458-464 (May) 1966. 27. Cauna, D.; Totten. RS.; and Gross, P.: Asbes tos Bodies in Human Lungs at Autopsy, JAMA 192:371-373 (May) 1965. 28. Webster. I., in discussion Thomson, S.F.. Physiological Effects of D;0 in Mammals, Ann NY Acad Sci 84:736-744, 1960. 29. Meurman, L.: Asbestos Bodies and Pleural Plaques in a Finnish Series of Autopsy Cases, Acta Path Microbiol Scand Suppl 181:107, 1966. 30. Anjilvel, L., and Thurlbeck, W.: The Inci dence of Asbestos Bodies in the Lungs of Random Autopsies in Montreal. Canad Med Assoc J 95:11791182 (Dec 3) 1966. - 31. Cooke, W.E.: Asbestos Dust and the Curious Bodies Found in Pulmonary Asbestosis, Brit Med J 2:578-580 (Sept) 1929. Part of a Study Simported by Public Health Service Rc:ircS C-rc.-t C-H CCtl-MC ard Gene, ol kesc-. c:i ora' I I-a;, Tr;-.i441-06 from the Natic.-.al Ir.st.turci of Health PUBLIC MEDICAL PROBLEMS We must stop this fragmentation in medicine as well as the fragmentation of our serv ices to the large indigent segment of our population. Our four public assistance medical programs should be one. And here I include prenatal, delivery and postpartum care, general hospital care for medical and surgical problems and the Head Start Project and school health program. Only in this way can we insure continuing supervision and con trol of disease. Consider the present situation in one of our larger cities. Families must visit, often simultaneously and also in another location, the health department for prenatal care, the county hospital for general medical services, the Head Start Project for their younger children, the school health program for those that are in school, the crippled children program if they have a crippled child, and the speech defect program for speech therapy. A typical pregnant indigent woman with four or five children must spend so much time and money for transportation to and from these nine separate so-called free services that it is no wonder she has no time or money to keep her family well, let alone happy.--Reis, R.A., MD: "Progress, Problems and Priorities," read before the AMA National Con ference on Infant Mortality in San Francisco (Aug 12, 13) 1966. Arch Environ Health--Vol IS, Sept 1967