Document qk8wwwYDgENOnaMDR9oReNa8n

WORKPLACE EXPOSURE TO ASBESTOS Review and Recommendations DHHS (NIOSH) Publication No.8M03 NIOSH-OSHA Asbestos Work Group April 1980 U.5. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Canten for Disease Control National Institute for Occupational Safety and Health VS. DEPARTMENT OF LABOR Occupational Safety and Health Administration November 1980 tm --to PrtaUm Offtc*. Doc--m. PJ. Owi P.C. 204K 21 CONTENTS MEMORANDUM ON ASBESTOS UPDATE AND RECOMMENDED OCCUPATIONAL STANDARD PAGE 1 L ASBESTOS NOMENCLATURE/DEFINITIONS Review General Definition 9 9 10 II. ASBESTOS SAMPLING AND ANALYSIS 12 m. BIOLOGIC EFFECTS OF EXPOSURE TO ASBESTOS IN ANIMALS In Vivo In Vitro 14 14 16 IV. BIOLOGIC EFFECTS OF EXPOSURE TO ASBESTOS IN HUMANS Amosite Chrysotile Croddolite Mixed Fiber Types Malignant Neoplasms other than Mesothelioma and Cancer of the Lung 16 16 18 20 21 24 V. SMOKING AND ASBESTOS 25 VL EXPOSURE TO ASBESTIFORM MINERALS OTHER THAN COMMERCIALLY MINED ASBESTOS VH. NON-OCCUPATIONAL EXPOSURE TO COMMERCIAL SOURCES OF ASBESTOS 28 30 Vm. DOSE-RESPONSE RELATIONSHIPS 30 REFERENCES 33 22 MEMORANDUM FOR: Dr. Eula Bingham Assistant Secretary for Occupational Safety and Health Dr. Anthony Robbins Director, National Institute for Occupational Safety and Health FROM: Asbestos Work Group SUBJECT: The Updated Scientific Information on Asbestos and Recommended Occupational Standard for Asbestos Exposure In the fall of 1979, a NIOSH/OSHA committee was formed at the direction of Dr. Eula Bingham, Assistant Secretary of Labor for Occupational Safety and Health, and Dr. Anthony Robbins, Director of the National Institute for Occupational Safety and Health (NIOSH), to review the scientific informa tion concerning asbestos-related disease and assess the adequa cy of the current OSHA occupational health standard of *2,000,000 fibers per cubic meter greater than 5 p.m in length (2Mf7m3). Since the 1972 promulgation of this 2,000,000 fim3 standard, OSHA, in 1975, proposed lowering the standard to 500,000 Pm3; NIOSH, in 1976, recommended lowering the stan dard to 100,000 f/m3; and the British Advisory Committee on Asbestos, in 1979, recommended lowering its occupational ex posure standards. The NIOSH/OSHA committee has reviewed the most recent scientific information, including documents concerning the above developments and the 1977 International Agency for Research on Cancer (IARC) review of the carcino genicity hazards of asbestos, and presents the following major conclusions and recommendations. A detailed updating of sig nificant scientific literature since the 1976 NIOSH Criteria Document and the 1977 IARC Monograph is attached. *Effective January 19, 1989, the OSHA Permissible Exposure Limit (PEL) was changed to 0.2 f/cc. Federal Register, Vol. 54, No. 12, pp. 2332-2983. 1. Definition ofAsbestos. Having considered the many factors involved in specifying which substances should be regulated as asbestos, the committee recommends the following definition: Asbestos is defined to be chiysotile, croeidolite, and fibrous cummingtonite-grunerite including amosite, fibrous tremolite, fibrous actinolite, and fibrous anthophyliite. The fibrosity of the above minerals is ascertained on a microscopic level with fi bers defined to be particles with an aspect ratio of 3 to 1 or larger. 2. Sampling andAnalysis ofAirbomeAsbestos. The committee concludes that the membrane filter-phase contrast microscopy method represents the only technique available that can rea sonably be used for routine monitoring of occupational ex posures and sampling for compliance purposes. However, the committee recognizes the lack of specificity of this method for fiber identification, and recommends the use ofsupplementary methods such as electron microscopy for fiber identification in cases of mixed fiber exposures. In recommending the primary use oflight microscopy, the committee also wants to stress the inability ofthis method to detect short asbestos fibers to which workers are exposed. The toxicity of asbestos fibers shorter than the 5-micrometer detection limit of light microscopy can not be dismissed on the basis of current scientific information. 3. Biologic Effects of Exposure to Asbestos. Animal studies demonstrate that all commercial forms and several non commercial forms of asbestos produce pulmonary fibrosis, mesothelioma, and lung neoplasms. Chrysotile is as likely as crocidolite and other amphiboles to induce mesotheliomas after intrapleural injection, and also as likely to induce lung neo plasms after inhalation exposures. Human occupational exposures to all commercial asbestos fiber types, both individually and in various combinations, have been associated with high rates ofasbestosis, lung cancer, and mesothelioma. While significant excesses of cancer of several other sites have been observed in exposed workers, presently available information is insufficient to determine the role of specific fiber types. On the basis of available information, the committee con cludes that there is no scientific basis for differentiating be tween asbestos fiber types for regulatory purposes. Accordingly, the committee recommends that a single occupational health standard be established and applied to all asbestos fiber types. Available data show that the lower the exposure, the lower the risk of developing asbestosis and cancer. Excessive cancer risks, however, have been demonstrated at all fiber concentra tions studied to date. Evaluation of all available human data provides no evidence for a threshold or for a "safe" level of asbestos exposure. Accordingly, the committee recommends that, to the extent uses ofasbestos cannot be eliminated or less toxic materials substituted for asbestos, worker exposures to asbestos must be controlled to the maximum extent possible. 4. Inadequacy of Current 2,000,000-Fiber Occupational Stan dard. The committee concluded that a variety offactors demon strates that the current 2,000,000-fiber standard is grossly in adequate to protect American workers from asbestos-related disease. First, the 2,000,000-fiber standard was designed in 1969 by the British Occupational Hygiene Society (BOHS) for the limited purpose of minimizing asbestosis. Disease preva lence data from the BOHS study population collected subse quent to 1969 strongly suggest that this standard is insufficient to prevent a large incidence of asbestosis. Second, all levels of asbestos exposure studied to date have demonstrated asbestosrelated disease, and a linear relationship appears to best de scribe the shape of the dose-response curve. These considera tions led the committee to conclude that there is no level of exposure below which clinical effects do not occur. Third, the absence of a threshold is further indicated by the dramatic evidence of asbestos-related disease in members of asbestosworker households and in persons living near asbestos-con taminated areas. These household and community contacts involved low level and/or intermittent casual exposure to as bestos. Studies of duration of exposure suggest that even at very short exposure periods (1 day to 3 months) significant disease can occur. Although various models can be and have been fashioned to postulate possible dose-response relationships involving as bestos, the committee believes that the limited current data preclude the creation ofany one empirical curve to describe the exact dose-response relationship. Over the last three decades, measurement techniques for asbestos have changed in several crucial respects, and there have been no suitable methods avail able to date to compare the results ofprior techniques to current methods. 25 In addition, no adequate epidemiological information is available on the disease experience of workers exposed below the current standard and followed for a sufficient period to identify long latent effects. Consequently, the committee can not present a precise dose-response relationship for the variety ofasbestos-related diseases. However, the committee firmly be lieves that compelling evidence demonstrates that prevention ofasbestos-related diseases requires that an occupational stan dard minimize all asbestos exposures, and definitely be set far below the current 2,000,000-fiber standard. 5. Recommended Occupational Standard for Asbestos Expo sure. Given the inadequacy of the current 2,000,000-fiber stan dard, the committee urges that a new occupational standard be promulgated which is designed to eliminate non-essential as bestos exposures, and which requires the substitution of less hazardous and suitable alternatives where they exist. Where asbestos exposures cannot be eliminated, they must be con trolled to the lowest level possible. A significant consideration in establishing a permissible exposure limit should be the low est level of exposure detectable using currently available ana lytical techniques. At present this level would be 100,000 fibers greater than 5 p.m in length per cubic meter averaged over an 8-hour workday. Regardless of the choice of a permissible ex posure limit, the best engineering controls and work practices should be instituted, and protective clothing and hygiene facil ities should be provided and their use required of all workers exposed to asbestos. Respirators are not a suitable substitute for these control measures. The committee also reiterates its judgment that even where exposure is controlled to levels below 100,000 fibers, there is no scientific basis for concluding that all asbestos-related cancers would be prevented. 6. Medical Surveillance Program. Appropriate medical surveil lance is crucial to detect and minimize the progression of some asbestos-related diseases. Considerable emphasis should be placed on baseline medical examinations for all workers poten tially exposed or who have been exposed to asbestos at any level. These examinations should include the following: (1) a 14* x 17* postero-anterior chest X-ray; (2) spirometry including forced vital capacity (FVC) and forced expiratory volume in one second (FEV!); (3) a physical examination of the chest includ ing auscultation for the presence or absence of rales, rhonchi. and wheezing; (4) an assessment of the presence or absence of finger clubbing; and (5) a history of respiratory symptoms and conditions including tobacco smoking. An occupational history should include a history of expo sure to asbestos and exposure to other substances of real or potential medical significance. Performance criteria for these procedures, including the periodicity of subsequent medical surveillance, should be developed by NIOSH in consultation with OSHA and professional societies and organizations con cerned with the diagnosis and prevention of respiratory dis eases. The committee does not recommend comprehensive an nual medical examinations as presently required. Sputum cy tology should be evaluated in the development of an improved medical surveillance program. The committee believes that sputum cytology may prove to be a valuable supplement to X-ray evaluation. It is also crucial that all required medical surveillance be promptly evaluated and the results reported to the employee. Furthermore, the standard should provide for periodic report ing ofaggregate medical information concerning an employer's entire workforce. Results at a minimum should be displayed in a non-identifiable, aggregate format so that the employer, em ployees, and OSHA can see the prevalence of abnormalities possibly associated with asbestos-related disease, and also see how this prevalence has changed over time. The committee recognizes that OSHA's recent lead stan dard contains a multiple physician review mechanism whereby workers can get independent medical evaluations by physicians of their choice. The lead standard also contains a medical re moval protection program whereby workers can obtain special health protection where necessary, accompanied by appropriate economic protection. The committee feels that these programs are relevant to asbestos workers and should be considered as part of a new occupational asbestos standard. Medical records generated due to the standard's medical surveillance program should be maintained for at least 40 years or for 20 years after termination of employment, whichever is longer. 7. Other Recommendations. The committee further recom mends the following: (I) Due to the widespread current and past uses of asbestos products in the maritime and construction in dustries, it is vital that any new asbestos standard address these industry sectors as well as other workplaces with employ ees exposed to asbestos. Regulation of these industries should be structured around the principle that where work must be done using asbestos, only those employees needed to do this work should be present, and only for the minimum period of time needed to complete this work. (2) Due to the sampling and analytical difficulties concern ing asbestos, manufacturers of asbestos-containing products such as construction materials should perform detailed moni toring ofexposures which could result from all foreseeable uses of their products, including misuse. This monitoring should include electron microscopy to identify fiber type mix and ex posures to fibers less than 5 pm in length. This monitoring data should accompany these products downstream so the users not only know that asbestos exposures may occur, but also know the nature of potential exposures. This monitoring data could, if appropriate, avoid the need for small employers who use asbestos-containing products to have to conduct monitoring on their own. (3) Due to the fact that other agencies regulate occupa tional exposures to asbestos (such as the Mine Safety and Health Administration), these agencies should be urged to participate in the development of a new standard and adopt this new standard. (4) Because cigarette smoking enhances the carcinogenic effect of asbestos exposure on the lung, particular emphasis should be placed on this in any educational program developed under a new standard. OCCUPATIONAL RESPIRATORY DISEASES Editor James A. Merchant, M.D., Dr. P.H. Associate Editors Brian A. Boehlecke, M.D. Geoffrey Taylor, M.D. Technical Editor Molly Pickett-Hamer. M.F.A. Division of Respiratory Disease Studies Appalachian Laboratory for Occupational Safety and Health U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Centers for Disease Control National Institute for Occupational Safety and Health September 1986 Disclaimer Mention of company names or products does not constitute endorsement by the National Institute for Occupational Safety and Health. DHHS (NIOSH) Publication No. 86-102 Ml* by tb* Superintendent of Document*. U.S. Government Printing Office. aehington. D.C. 20403 ASBESTOSIS John M. Dement James A. Merchant Francis H. Y. Green INTRODUCTION Occupational exposure to asbestos minerals constitutes a major health hazard in the United States and in most industrialized nations of the world. Because of their unique properties such as resistance to heat and chemical attack, asbes tos minerals have long been used by man. Fin nish potters are known to have used soils con taining anthophyllite asbestos dating from 2500 B.C. (103). Use of asbestos in lamp wick was described by Theophrastus, Strabo, and Plutarch. Herodotus (456 B.C.) described cremation clothes made of woven asbestos. Marco Polo described tablecloths of asbestos seen during his journeys (66). Despite early uses, large scale use of asbes tos came with industrialization and particularly the steam engine which required heat resistant materials for packings and seals. The first as bestos textile mill in the United States began pro duction in about 1896. Today, commercial uses of asbestos are countless and nearly every manu facturing sector may be involved with produc tion or use of asbestos-containing products. The term "asbestos" is applied to a group of naturally occurring fibrous silicate minerals. Although many minerals are Fibrous in nature, only six are regulated by Occupational Safety and Health Administration (OSHA) standards. These minerals fall into two major mineralogical sub divisions: chrysotile, which belongs to the serpentines; and the amphiboles, including crocidolite, asbestiform actinolite, asbestiform tremolite, amosite, and anthophyllite. Only am osite, chrysotile, and crocidolite sue of economic importance. Chrysotile is basically a sheet silicate mineral rolled into itself to form a hollow tube. This tube constitutes the basic fibril of chrysotile. All amphibole asbestos types are similar in crys tal structure: they consist of double chains of linked silicon oxygen tetrahedra between which metallic ions are sandwiched (128). Chemical composition and trace metal contamination (Cr, Co, Mn, Ni associated with chrysotile) of as bestos Fibers may vary considerably between deposits from different mining regions (43). More than 90% of all asbestos used in the United States is of the chrysotile variety. Total U.S. consumption of asbestos in 1977 was 610,000 metric tons, down from peak comsumption of 795,000 metric tons in 1973 (12). By con trast, only 93,000 metric tons were produced in U.S. mines and mills; Canada furnished 95% of all imported raw asbestos fiber. U.S. asbestos consumption by end use for 1978 is shown in Table II-9. Asbestos cement products constitute the major use of asbestos followed closely by floor products or materials used in the construc tion industry. Materials containing asbestos have been extensively used in construction and ship building for purposes of fireproofing and for decoration. These have often been applied by spray application. DEFINITION Asbestosis is the name of the pneumo coniosis produced by the inhalation of asbestos fibers. It is characterized by diffuse interstitial fibrosis of the lung parenchyma, often accom panied by thickening of the visceral pleura and sometimes calcification of the pleura. Clinical findings include dyspnea on exertion, non-pro ductive cough, rales at the lung bases, bronchi, and in advanced cases, finger clubbing. Lung function measurements usually demonstrate a restrictive impairment with reduced diffusing capacity. Table II-9 U.S. ESTIMATED ASBESTOS CONSUMPTION IN 1978 BY END USE CATEGORY Product Asbestos cement pipe Asbestos cement sheet Flooring products Roofing products Packing and Gaskets Thermal insulation Electrical insulation Friction products Coating and compounds Plastics Textiles Paper Other Chrysotile 119,800 28,400 122,400 58,200 23,200 14,300 3,200 81,000 29,100 5,300 5,700 28,400 33,100 Consumption (Metric Tons) Crocidolite Amosite 23,300 2,700 800 100 100 Anthophyllite 600 500 700 2,100 Total 552,100 Source: (12) CAUSATIVE AGENTS Asbestosis is perhaps the most widely stud ied of the known occupational hazards; however, its mechanisms are still not fully understood. Both clinical and epidemiological data have con clusively shown that asbestos is associated with asbestosis and respiratory cancer in man. Animal bioassay data fully support these findings and suggest that pathological responses to asbestos may be more related to physical characteristics of the fibers than to chemical composition. Animal data have shown a wide variety of fibrous minerals and small diameter glass fibers to be capable of producing tumors upon pleural injec tion or implantation (110X111X139). Interstitial fibrosis has also been produced in animals in tratracheally injected with small diameter glass fibers (63). POPULATION AT RISK Asbestos has over 3,000 commercial uses and is ubiquitous in the general environment. Because of the mineral's resistance to thermal and chemical degradation, exposures may take place starting from initial mining of the fibers through manufacture, use, and eventual burial of asbestos containing waste. Mining and milling of asbestos in the United States is not extensive: fewer than a thousand workers are employed (148). However, amphibole 24,700 3,500 2,700 minerals and, to a lesser extent, serpentines, are sometimes found as contaminants of other types of ore bodies, such as talc, vermiculite, crushed stone aggregates, and in ores from various metal mining operations (19X64X115) (140). There have been no systematic studies of mining operations in the United States to identify specific ores con taining asbestos as contaminants and the degree to which workers are exposed. Estimates of the number of workers exposed to asbestos in primary manufacturing of asbestos products are given in Table 11-10. In the primary manufacturing sector approximately 18,000 work ers are estimated to be potentially exposed; how ever, this number could be as high as 37,000 (17). A large variety of asbestos products and materials produced in primary manufacturing are fabricated and processed with other materials in secondary industries to produce the more than 3,000 end prod ucts containing asbestos. The secondary fabrica tion and processing industry is very large and has been estimated to employ more than 300,000 work ers (17). By far the largest number of workers with potential asbestos exposures may be found in in dustries which utilize asbestos products such as the construction industry, the automobile ser vicing industry (including remanufacturing of 32 Table IMO ESTIMATES OF WORKERS EXPOSED TO ASBESTOS IN PRIMARY MANUFACTURING Estimated Number of Potential Manufacturing Sector Exposed Workers Asbestos cement pipe Asbestos cement sheet Friction materials Floor coverings Asbestos paper products Packing and gaskets Paint, coating and sealant Asbestos textiles 1,755 980 5,605 3,500 2,120 1,125 815 1,800 Total Source: (17) 17,700 asbestos containing parts), and the shipbuilding and repair industry. In the construction industry, including those doing demolition and repair, an estimated 180,000 to 408,000 workers are poten tially exposed to asbestos. The automobile serv icing industry includes brake and clutch servicing garages, rebuilding and refacing friction com ponents, and repackaging of friction products. Within this sector, 2 million workers are poten tially exposed to asbestos (17). Approximately 3,800 workers are potentially exposed to asbestos in shipbuilding and repair. A total of 2.3 to 2.5 million workers are estimated to be currently (potentially) exposed to asbestos. However, because of the long laten cy (20 to 30 years) required before asbestos re lated diseases become clinically manifest, past asbestos workers must also be considered at risk. These estimates are especially difficult to develop and are subject to controversy (29). Nonetheless, large numbers of previous asbestos workers are now completing their latency period and are at risk of asbestos related diseases. EPIDEMIOLOGY Early Observations Asbestosis The Erst well documented case of asbestosis was reported by H. Montague Murray in 1906, although there were several anecdotal reports prior to this time (66)(95). Murray documented a case of pulmonary fibrosis at autopsy in a worker engaged in the production of asbestos textiles. This worker reported that he was the sole survivor of 10 men who started with him in the carding room; the others had died. Following the report by Murray, Pancoast et al. (1917) reported 17 cases of pulmonary fi brosis in a Pennsylvania plant (105). In 1924, Cooke published another detailed autopsy report of a 33-year-old woman suffering from asbestosis (14). Necropsy findings included pulmonary fi brosis, pleural thickening, pleural calcification, and heart enlargement. Further cases were report ed by Mills in 1930, Donnelly (1933), Lynch and Smith (1931), Seiler and Gilmour (1931), Wood and Gloyne (1930), Oliver (1927), Simson (1928), Stewart (1928), and Pancoast and Pendergrass (1926) (21)(70)(88)(104)(106)(120)(134)(141)(164). By 1930, more than 75 asbestosis cases had been reported in the literature. Early case reports stimulated concern and in 1928 the first detailed epidemiologic study of asbestos workers was undertaken by the Ministry of Labour in Great Britain. Results were pub lished by Merewether and Price in 1930 (84). This was a cross-sectional chest x-ray study of 363 workers engaged in production of asbestos tex tiles. Of this group, 95 (26.2%) were found to have pulmonary fibrosis and the prevalence of fibrosis with 20 or more years employment was over 80%. In the United States, Donnelly (1936) report ed a cross-sectional chest x-ray study of 151 asbestos workers which found a pulmonary fi brosis prevalence of 59% among workers em ployed 4 years of more (22). Schull (1936) report ed chest x-ray studies of 100 workers dismissed from North Carolina asbestos plants due to dis ability and found a 55% prevalence of moderate or advanced asbestosis (131). . In 1937 the U.S. Public Health Service undertook the first detailed epidemiologic study of asbestos workers in the United States with results published by Dreessen et al. in 1938 (23). A total of 511 employees were studied in this cross-sectional study and worker exposures were estimated by the impinger method. A relation ship was found between extent of asbestos ex posure and clinical symptoms of asbestosis al though many workers had only short periods of exposure at the time of the study. This study re sulted in a recommended occupational exposure limit of 5 million particles per cubic foot of air (mppcf) in the United States. Lung Cancer and Mesothelioma The first indication that asbestos might be a human carcinogen came in 1935. Lynch and Smith (in the United States) and Gloyne (in England) independently reported three cases of lung cancer detected during autopsy studies of asbestos workers (34)(71). All three workers had died of asbestosis. Other case reports followed by Egbert and Geiger in 1936, Gloyne in 1936, and Nordmann in 1938 (26X33X102). In the 1947 annual report of the Chief Inspector of Factories in England, Merewether stated that of 365 asbestosis deaths, 65 (17.87b) also had cancer of the lung at autopsy (83). This compared to a prevalence of lung cancer of only 1.37o for cases certified at death as having silicosis. Despite early suggestions, the first detailed epidemiologic study to conclusively demonstrate an association between asbestos exposure and lung cancer was not published until 1955 by Doll (20). Doll studied the mortality experience of a cohort of 113 asbestos textile workers employed more than 20 years. Among this group, 11 lung cancer deaths were observed compared to only 0.8 expected--based on the mortality experience of England and Wales. Asbestos exposure is associated with mesothelial tumors of pleural and peritoneal tissues. Lee and Selikoff have reviewed early reports associating asbestos exposures and mesothelioma (66). The first cases were reported in 1946 by Wyers (165). However, conclusive evidence of an association between asbestos exposure and mesothelioma was not available until 1960 when Wagner et al. reported 33 pleural mesotheliomas in the crocidolite mining area of South Africa (152). Mortality Epidemiologic studies have repeatedly dem onstrated an association between asbestos expo sure and increased mortality due to asbestosis, lung cancer, pleural and peritoneal mesothelioma, and gastrointestinal cancer. In some studies, asbestos exposure has also been associated with increased risks for laryngeal cancer and cancer of the buccal cavity and pharynx. Table 11-11 con tains a brief summary of important mortality studies and significant findings. In this section, mortality studies are reviewed with emphasis on asbestosis and lung cancer risk differences by fiber type, industry, and smoking patterns. Mixed Fiber Exposures In most plants processing asbestos, several different types of asbestos may be used or have been used in the past. Typically, chrysotile and one or more amphiboles are used. Asbestos insulation workers have been ex tensively studied in the United States and other countries. Selikoff et al. studied the mortality ex perience of 632 insulation workers followed be tween 1943 and 1962 and observed 45 lung can cer deaths whereas only 6.6 were expected (123). Of the 255 deaths in this cohort, 28 (117o) were due to asbestosis and 3 (1.27o) to mesothelioma. An SMR of 309 was observed for cancer of the stomach, colon, and rectum (although it was based on a small number of observed cases). A much larger cohort of 17,800 insulation workers was followed by Selikoff et al. between 1967 and 1976 (126X127). Among this cohort, 2,271 deaths were observed including 429 lung cancers (SMR-406), 78 asbestosis deaths, and 49 deaths due to mesotheliomas. Significant in creased mortality was also observed for cancers of the esophagus, stomach, colon-rectum, lar ynx, buccal cavity and pharynx, and kidney. Only 2 of the 78 asbestosis deaths occurred prior to 20 years from onset of employment, based on death certificate information. Review of all available autopsy, surgical, and clinical material indicated an additional 90 deaths were due to asbestosis, 57 to lung cancer, and 126 to meso thelioma. Elmes and Simpson studied the mortality of 162 insulation workers in Belfast between 1940 and 1975 (27)(28). Among this cohort, 122 deaths were observed including 16 (13.1Tb) due to asbestosis and 13 (10.77o) to mesothelioma. A large excess due to respiratory cancer was observed. There are several important studies of mor tality among textile workers exposed to mixed asbestos types. In an early study in the United States published in 1963, Mancuso and Coulter observed more than a threefold excess risk of lung cancer among workers producing textile and friction products (73). Fourteen percent of 195 deaths were due to asbestosis and 2 (17o) were due to mesotheliomas. Mortality among employees in the plant in itially studied by Doll in 1955 has been in- Table 11-11 SUMMARY OF M O R TALITY STUDIES OF ASBESTOS EXPOSED POPULATIONS ewOfi 9e c>j n u Cu |S. ^2 to 3Mf 6C0J 4- rj m ^CC* *--rotfc re ^ Qj c S S&l CEsA = owo ccj --o 50 W) e nc JS a -Sd oCJ O' c ^ if) 75 5/5 g 50 $> 2 > J CJ U .3 CJ a > u CL o 50 o 50 CJ > 50 3 50 n 50 Cr-J o tko> 3 CJ CJ CJ CJ CJ CJ c CJ d $ OO re X M re CJ CJ COO nC in= 5/5 <r 3 J 2 3CJ 2 00 a 5/2 (i _ " (8 2 j o {>o22: 5G ( !r. ^ c '(A 60 o xj re CJ tz o 60 o d 73 CJ X5 50 re <N 5k0. CJ CJ c re CJ CJ e CJ CJ d C/^ CJ X CJ c w/-s 50 CJ S2 5k/2. 5CJ/25,. >-s| o -- 3 4> j- 3 >|c I * -i " ro Sg TyC3J O-->' Sis CcJ w5J 4k./ -o.E 2 T3 S w _ i> u x-e ? Jp-8 I? tCoJ 3 00 5/5 r- d <N -- e O 3 60 2 -- CJ Q0 = c O5C/5J 5/5 o C55//J52 <G _xu 4> -X o ocoo <TN* re O&OC0 00 o re Eecs . 3 ^ I rs cj co--o S5ro C/5 cj S.2 a*cj cxj JtZ: (N { oo *5 kC>aJ .JC3J O 111 i_ cj " o iaOf) 1 *CJ tCC_oJJ MC-- J5CZ0J <U0 wCO.2^P 00 D. H J 8e rr S -- O >5 o 0 *3a5* a JZ ocj C>J >9> 3 55 cCCtOoJj. t- m Or<msmni' SS o JZ oCJ C>J OV Ovf D.ON 5/5 mm 2d w2 oO<j c>j UdCJ <SONO' 5/2 mm 2d IS JoS ocj C>J CCCJJ. NsOoOs 5/5 --I 2d o oCJ C>J tCQJJ.OoSNOo 5ok/_5 m IS o ocj C>J CCd50JJ ooS--Oo 2d IS H TCX3J o >5/5 Jc=j O 2 VXo CaJ X o ft, T>33 55 C>Js u50 JU XCJ o d rC>eJ, CJ CJ to Ck>J ka o fan m -- Ok. o 5 O CN CJ 50 CJ 60 JkCX>J k. o --CxJ' *O33 oo c ka d "G c n OtT' *3O3 o o -- k. d OmnN mNOO' c o _re 3tCo J.r=s J to CkJ. rtwC>oeJs CJ k> o cCJ cc>s o C<TN2 Oka *d o J o <N CJ 'OO' CXJ 5/5 ka ^ -X o - oj mOOi' oOOo' TC3J TC3J XX MCXJ 5k/2. 8CJ sn o Tf ? OnOCn' mrO-' CJ 3 T3 ici -Ca 2o. .CEJ cj co m nO' rw3uCmy CrONN 3O U o c3 o a e3o Ck-O J3Z U o .c Jr- o o| c/53 3X re xoc re JO3= O3 ?CJ CJ ZZ workers Approximately threefold excess o f respiratory disease m ortality in this group. Overall 1 mesotheli- 35 Table IM 1 SUMMARY OF M O R TALITY STUDIES OF ASBESTOS EXPOSED POPULATIONS (Continued) u ,<L* 9 B fg ** re 4>a> S 2> a - w yo5 X) o _ g-S ll 2*" CA 60 .2 2 T3 g m E al<"2 2 .^oa tS <a O C 60 S w E x m> qj c E <sn fgc S3o 0 O; v ^ 1E =a 4> O3 E* (A JS Oo3o O -U n5 X5 ~ a &> &> qo 73 13 .2 J 2 fe <A 2 > ca re 2 = J55 Eo 2 i re x fll vx a2 2o w ro>e% CA o *4=* C o c. _or-4 A }- 2 Eo -J CA II 0.-0 cti_a --3re fij k. oo .rE* E rue fvj oo ^ -- *o oCA k. 2t> g u II f S 2 oo |re _ o re <A W Oo 2S 5o> >wc; E < 3[M <'--CNl *Tu3 *.2 5OO o Ec^ =lf 1 X2 W- Q= 2O *>2 | 2Eco^So3c. V CA U h. 2 ^O I!t| <or*s* 7b3 It B ou. **- <vNo - g; _ c a: J *8**1 C/3 jy- JS mrtemj O' ?? !"! |l| 6 28 & *n * *00 (O CA .ts ^ W j 2 y2- ^? rCe k>as y ; 2 >5 2 t>o> 25qj .--I2 xO0rw0e og E n* 2 2*0 oo&g CV_ O' re TNt -- -O CA X op QJ 3t. rye* ois y> ^V CA Cre O . ^ w CA CA ^ I< 00 2 22 s s IXX . ca <n sx E o re 2 2r w .- O i "I <S 2? o DC Cre -4O> uCA U lx 3 coo o^a E _o Xs xO c -- m3 N -- X S 1 8s fc .E 'i * K S 8. o X ou >4> yt> ps~o- a Cl Os 55 (OtA- m--' SI ou >o t> V a Op~' CA mm -oC oo a>> moyOm. rO-' CA mm no Va >> H *D V X T3 VX U a "a& e JS (A co> flu (A | I &o n t0o<N aP m JA S oo re fi NO On re 3 CA <A k C 4> -- -X <N Q 2g -- Pp r- O' O' CA o CA i-g CreA Gre ror>O' CA k CA L. c= -- EE -r-nr-'Or-'Ooo O' O' O' O' ooy y> mOVm p. Cl O' OCA 85 2 o crWi>e uCA 3 o o .-S 2 j= uT D. XS u o o O u. .3 a. ^ i/i y ca. X) r- CA .X k> X) -- re JO. CA <r-s or~o O' O' Ou o _> O NO V P" o.o> CA mm Sri Ou 4>> 4 P~ X O' CA v 2nd m *2 x>a, -a o x X c < 23 CA C cA aSs00? oS- k. es CA -- O r= C4A X "O mC W ca 5^ vx 8..S. 5. --E? O' p~ p O' O' p^ O' *T3 c C o o CA E c. re Ea E K v X oo T3 2 : x cre * c ou avs ~co c/3 a vCA E E o Q y o c c vo --.1 2o 2*S WX re cre o E k. "a> 34> C/D 36 Table IM 1 S U M M A R Y O F M O R T A L IT Y STUDIES O F ASBESTOS EXPO SED P O P U LA TIO N S (Continued) m E E 3 sW o X cw 00 TJ C . wO CO cWo 1 2 1/5 co 3: s w1/5 "^ S 8 v O S.s sS *0 .& 2 Cm <U mO CO On - 1/5 3 w> Q. E L> ^ so CC1w//O55. 'XcCCe0OO0 E *<0 00, 2 CO cd 2* m *d w iI Sg C/5 W u 5 o 4> 1/5 2Z .2 x C:g eo 2 tS 2 A3 *o5 3 73 fc> Cv/5 X) N 1/5 10 8 E * L- (N O u oe 3 Li sk/5. 3e wI eeo o 4>/ r"- OC/5 co Ew J= O l vweo?. eeWB e.SSW3 X 0J O* . IbS * * -Wc Co S| O W c: 8 X) B O e o -- Cj2 8c ~Is W E-g ko. e- O cA Cd T3 cB Wco wco *wa*/ ^c_3o wc ax p5 J3 Li jg (--S cNnO *--<w* Cm W J & s I. Li 1 o. a co e A O cLoi XW W2O W k. B V EE *L>oi A e o ^ eW ^io E.&o f s RS _* we . 5 twQs, L&coi X -D WO w 5a. ~ CO 'C Wk. STuO O Li "fOe X*ws O ^ co ^ S2 _eeEo E --o w3O' es X Si/5 t.32^i_ cwo "wO o. O' sell E *X CQ 3 O. O 3X eo *-- 6s _ L> fen Oco W co 00 X O CO a e2 w8 oo _c3 cWXl <r^j5 O' o Xow l>> T9 lt>> CL Li 0* o x o Li L>i LCi. pO' C/5 m {w5 S2 o X o Li w> O NO wa. r on C/5 -- Ot- OJ' si {52 C3L =t o W .> rr 8CcOoL ov2o. 2 o JoZ Li _W> OL> fr^-5 Oco.OWN ok. o> wS cc 2 H lW_ A *WXo T1>3/v O *&3 = I e fi. UX i/1 (23 >% 3 -- o2 35 -- * A rr~-~ or~n~ O' O' _w o C/5 >1 Xk> o 1/5 Wh_ _X ecOo o wg-*2c3 s| <N B rpO~' o ;g "o3 k* U .x 00 CnO E CO oo <2A -- ,, O00O w u. -- -^ o oC - NrO- Or-' O' O' wXa w 2S i Is! p. co run CO OCNN -->> O k3. W ^ ^ o. NrO- Or-' O' O' *ceo oj 3 &8 2o c CO k. Xwceo wO>^ *r> NVT5 LtJi OOr~'' 4/ a. T33 (0 co co r e 4/ o 3 LJ < CL <0 9J T3 ee ^5 Li oo *o XL300i UJ X >20 years latency cumulative fiber exposures>100 m ppef/yr.; 2 pleural meso theliomas observed versus 4.4 ex pected among those not exposed to crocidolite. 37 Table 11-11 SUMMARY OF MORTALITY STUDIES OF ASBESTOS EXPOSED POPULATIONS (Continued) IIs S 111e u 3 8 gm B Ba Gf> 00 s eo.e w C0 -5- w0 C * J5 g CM 3 m *3 < XI c OI (U<0i, ,t<U---d ue O 3VM*.MB 3o>.2 S 2 c*0 .Qs.-au 3 <S 2a *o3> >. if t3 o u E NO 4= *--> > II Jw2 ^ 3V *5. ^ ^ cO 3O a- *8 f) co %0v>0i tS0>;0 Is w 3M c3 oQ> J7Z2 x%i (A is ( 5 >6 4/ ^ --3"M ^ka oMo cn 5M O4S1fl c5O .t. kO>. o 5 e-- fl 2 ^2 o2 u0/ o3 .o c3 e *3 00*3 I=X>-sC3 4> *u .u3 Ou *3 JS .vS. Jo s c S-o E Crt Soi wV w> Ot> .0B2J0 iri 3 4> t> Q, u o oSo x >o sfc5 -- O^ag nCOrNi E(I Su * wo>**--22 aD. ut 2 o **" *mS o *3 ft c2,g o 3 *K *S *3 3 00 w C a .>o s i . <_ co Eg ms 3^ M 2O *3 u 4> O o E *3 .2 C W a" is x *- *2 c o -- IA o 00 g O -o *3 *-- (4A> wt> "3 O 3 O 115 s-S Eou 09 w. RlS _C AS-SO J? E b8 8u |o gu nO O2.2b S S ow . *3 1/3 4/ n^ 2E occ 3 'mo ^^v --ll j`~/ --3 01 g.S w tf! 2w E433 kK. ^* i5 Cv E o 3_ ^2 o3 8*0 Q.-3 g c E wi E "l' W 8 ; c 3 4> S *3 W *gO = 3-- SEV S g k. I = s E O bo- C/9 3o -2J r--> a 3I * o 4> VO 4> X. 05 cf/i. , IOu*-- Oo u> okj vpn- Q.O' Si oo v> 8O- .O<r-c' M Sri 21 o V i>f to> *rr-> G. O' 26 Si &> .o *VX3 ft> t- ae. *^>o2, .^t%s5 J=|a5-,--~*= ao 55 ^^ Ow (8 k. JSS ft u 3 O. 2 nj 9JJSaow. O' S rO-v w o E < 0c0 *-3wo o o O. c r> c4g> OSO' 7 S 5S .S2 O' p O' *3 V X c .2 iS -c 1/3 :g8>, g Jc ^ c fc 4> w On - - ?A O' r" O' Oua >% u. JuZ >t o ----J (/) w o2 UT3 ob CQO as -c c SS-3-2 CM 0.2 rn ai Or--' O' BO r e ov x: C/9 38 Ii wv oe |i 3*3 VC C/9 3 c 4> if C/9 Eif -3* J u C o g& E C? 3 X ao: 3l Table 1M1 SUMMARY OF M O R TALITY STUDIES OF ASBESTOS EXPOSED POPULATIONS (Continued) a m O - e 2s S B SB te sisSB s s S.Stgafl a . %1 O 2 *E >g 4> SA a 3fc (A a " o O v D.T3 --. .. t fucCol8j cqo 3 .4o>. *>o D$ 56 &Q..O2 ac xV o 5 A 4 00 <N -- O JwS 3<A (A 3 Vo 00 C = W * X .22 0 t2Os a Sgo 3 a u 3SaISO 42S N^ II o O in g o * s-1 V ..6 ac U ^ C 2 o 'O VQ. Ca u^ i-f o <- 3 O^l * g. u ux a4> uCJ s <n ^ r-- S "O J uS B Oft o JuoS s fi >o> If: a o.\ 35 2* O JooS >V om &S obA Mp* si 2. H L> | Eh o (>A* 3 o (A it at aa O-g e (A C (A g 3 >i* C9 a t JS CJ A 5 >> o x u -- -x 3m fcSAS *Iv 0ir0- A2S ft) Q r*s\ o 00 S c " (A Eb fj H 2E 00 "O ms Ca t-s V eo 5 e 5A re o <A o JuS a B e Q C 2 fc- |a qa a i* o c CD 39 vestigated by Knox et al. (59)(60), and more recently by Peto et al. (108)(109). Peto studied 1,106 men and women who had worked 20 or more years in asbestos exposed areas. Among those who were first employed after 1933 (when control regulations were enacted), 31 lung can cer deaths were observed whereas 19.3 were ex pected. Additionally, 35 deaths were observed due to nonmalignant respiratory disease versus 25 expected, and there were 5 deaths due to pleural mesothelioma. Dust exposures in this plant were reported to be generally above 5 fiber/cc until about 1970. Newhouse (96X97) and Newhouse et al. (98) have studied patterns of mortality among 4,600 male and 922 female workers in a plant which chiefly produced asbestos textiles but later as bestos insulation products. Exposures were clas sified as low to moderate (5-10 fibers/cc) and severe (>10 fibers/cc). Among males, there were 46 mesothelial tumors and an SMR for lung cancer of 538 was observed for those employed more than ten years in the severe exposure group. In those with lowest exposure, a lung cancer SMR of 154 was observed. Deaths from chronic respiratory diseases were 1.8 times expected in the highest exposure group. A remarkable cancer SMR was observed among females in the highest exposure group (21 observed versus 0.8 expected). Both males and females were found to have smoked more than the comparison population; however, this could only account for 10% to 20% of the observed excess lung cancer mortality. The asbestos cement product industry is one of the largest consumers of asbestos in the United States. In addition to their asbestos ex posure, workers in this industry may also be ex posed to low levels of crystalline silica and other materials associated with cement dust. Weill et al. reported mortality patterns among 5,645 asbestos cement product workers with a mini mum of 20 years since initial employment (156). Exposures for the cohort were estimated and ex pressed as mppcf x yrs. Among those exposed to greater than 100 mppcf x yrs., 23 lung can cers were observed versus 9.3 expected. No ex cess lung cancer risk was reported among those with cumulative exposures less than 100 mppcf x yrs. Two pleural mesothelioma deaths were observed. Weill et al. reported that exposure to crocidolite in addition to the (predominant) chrysotile used in cement products increased the lung cancer risk in comparison to chrysotile ex posure alone. The unusually low SMRs for all causes regardless of exposure category suggest that cohort follow-up and death certificate ascer tainment was less complete than desired. Crocidolite Wagner et al., in 1960, reported 33 pleural mesotheliomas among men working in crocido lite mines and mills and the population living in the vicinity of these mills in the Northwest Cape Province of South Africa (152). The high in cidence of mesotheliomas in this area has been confirmed by other investigations (13)(39)(155). Crocidolite was commonly used in the pro duction of gas mask canisters during World War II and mortality among these workers has been investigated. Jones et al. studied the mortality of 1,088 workers exposed between 1940 and 1945 and followed through 1976 (46)(47). Twenty-two pleural and 7 peritoneal mesotheliomas were ob served and a linear relationship was observed bet ween employment duration and the risk of mesothelioma. There was also a modest excess of bronchial carcinoma. Similar results have been reported by McDonald and McDonald who studied a smaller cohort of gas mask workers in Canada and found that 7% of all deaths were due to mesotheliomas (75). Amosite Mortality patterns among a cohort of workers producing amosite asbestos insulation between 1941 and 1945 have been reported by Selikoff et al. (125) and more recently by Seidman et al. (118X119). This group of 820 men were observed over a 35 year period during which 528 deaths occurred: by death certificate information 15 (2.8%) were due to asbestosis and 1 was due to mesothelioma. Review of available surgical, pathological, and clinical data for this group identified 13 additional mesotheliomas and 15 additional cases of asbestosis not listed on death certificates. Overall there were 83 lung cancers observed whereas 23.1 were expected and among those employed less than one month, 3 lung cancers were observed versus 1.3 expected. Anderson et al. have observed four confirmed cases of mesothelioma among household con tacts of workers at this plant (1). 40 AnthophyHite and Tremolite The only location in the world where an thophyllite has been commercially mined and processed is Finland. These ores are also known to contain smaller quantities of tremolite. Mor tality among workers in two Finnish mines and mills has been studied by Meurman et al. (86) (87). In their first report, 1,092 workers were followed from 1936 until 1974. A relative risk for lung cancer of 1.6 was observed and there were 13 (5.2%) asbestosis deaths but no deaths due to mesothelioma. Their subsequent study concerned 793 workers with known smoking his tories with 10 additional years of follow-up. A relative risk for lung cancer of 19 was observed for smoking asbestos workers and 1.6 for asbes tos workers who did not smoke. Asbestosis mor tality was found to be equally frequent among smokers and nonsmokers. All lung cancer cases with more than 10 years of exposure were also found to have asbestosis. Chrysotile Chrysotile is the major asbestos fiber type used in the United States, but most of this fiber is imported from Canada. The mortality of Quebec chrysotile miners and millers has been extensively studied by McDonald et al. (76) (79 81). The most recent report for this cohort in cluded 10,939 men who had been employed one or more months and followed between 1926 and 1975. An overall SMR for lung cancer of 125 was observed; 42 deaths were due to asbestosis and 11 to mesothelioma. A nearly linear doseresponse relationship was reported for lung cancer. Increased mortality was also observed for cancer of the stomach and esophagus but no other gastrointestinal sites. Similar patterns of lung cancer and asbestosis mortality have been reported by Rubino et al. in Italian chrysotile miners and millers where an SMR for lung can cer of 206 was observed among those with suf ficient latency (117). The McDonald et al. studies demonstrated a low lung cancer risk even in the highest ex posure group. Nicholson et al. have reported larger excesses from lung cancer and asbestosis in their study of chrysotile miners and millers in Quebec (99). This latter study cohort consisted of 544 miners and millers with at least 20 years seniority and followed between 1961 and 1977. A total of 28 lung cancers were observed versus 11.1 expected (SMR = 252). There were 30 deaths due to noninfectious respiratory diseases whereas only 6.7 were expected. Of these 30 deaths, 26 were due to asbestosis. Only one mesothelioma (pleural) was observed. Mortality among chrysotile asbestos miners and millers in the Urals has been investigated by Kogan et al (61). The overall cancer mortality risk was found to be 1.6 times that for the general male population and was higher in mining than in milling. Among males, the relative risk for lung cancer was 2.0 and ranged from 1.4 to 2.1 for females. The lung cancer risk was con siderably greater in older age groups having the longest latency. No mesotheliomas were reported; however, Kogan et al. attributed this to insuffi cient experience of pathologists in that geographic area (61). Nonetheless, the low mesothelioma risk is consistent with other studies of chrysotile-exposed populations. There have been several studies of factory populations exposed only to chrysotile. Weiss studied a small cohort of 264 workers in a plant producing asbestos millboard and reported no excess cancer mortality (160). However, there were only 66 deaths (2 of which were due to asbestosis) and cancer latency was not taken in to account in the analysis. A facility manufacturing asbestos textile, friction, and packing products has been studied by Robinson et al. (113). Chrysotile constituted over 99% of the total quantity of asbestos pro cessed per year in this plant except during World War II; the remaining 1% was crocidolite and amosite. The cohort consisted of 2,722 males and 544 females followed between 1940 and 1975. Among males, an overall lung cancer SMR of 135 was observed but among females the excess lung cancer risk was much higher with an overall SMR of 824. There were 76 deaths in males due to noninfectious respiratory disease but only 16.4 expected. Again, the chronic respiratory disease risk was higher among females with an SMR of 1,555. There were 4 mesotheliomas among fe males and 13 in males. Dement et al. have reported mortality among a cohort of asbestos textile workers ex posed only to chrysotile (18). This cohort con sisted of 768 white males employed at least 6 months and followed between 1940 and 1975. There were 26 lung cancers observed versus 7.47 expected. Of the 191 deaths in this cohort, 15 (7.9%) were due to asbestosis or pulmonary Fibrosis and 1 (0.5%) was due to a peritoneal 41 mesothelioma. Linear relationships were demon strated between cumulative fiber dose and the risk of mortality for lung cancer and noninfectious respiratory diseases. An SMR for lung can cer of 223 was observed for the lowest cumulative exposure category of less than 30 fibers/cc x years. Fibers and Asbestos-like Contamination of Other Minerals Both serpentines and amphiboles may be found as contaminants in other mined and pro cessed ores and may result in significant fiber exposures to workers in these operations. Fibers and cleavage fragments of fibrous grunerite occur where ore from some iron for mations are crushed and comminuted and have been found in high concentrations in Lake Superior as a result of mining and milling opera tions (64). Gillam et al. studied mortality among gold miners exposed to cummingtonite-grunerite and found a threefold excess risk of lung cancer and a twofold excess of nonmalignant respira tory disease, excluding influenza and pneumonia (32). However, workers in this mine were also ex posed to silica. McDonald et al., in a subsequent study of the same mine, examined the mortality experience of persons with at least 21 years of employment with the company (78). This study demonstrated excess mortality due to pneumoconiosis (mainly silicosis), tuberculosis, and heart disease but no overall excess of malig nant diseases was found. However, when the population was stratified by exposure, respira tory cancer was elevated (but was not statistically significant) in the highest exposure group. Commercial talc deposits are sometimes found to contain serpentines (chrysotile, antigorite, end lizardite) and fibrous and nonfibrous am phiboles. Kleinfeld et al. demonstrated sig nificantly increased proportionate mortality due to lung cancer and nonmalignant respiratory disease among talc miners and millers in New York State exposed to fibrous anthophyllite and fibrous tremolite (53)(58). Brown et al. have reported a further mortality of talc miners and millers in one company mining this same ore body (9). This cohort consisted of 398 workers followed between 1947 and 1975. Among this cohort, 10 respiratory cancers were observed whereas only 3.5 were expected. Approximately a threefold excess risk of nonmalignant respira tory disease was reported; however, only one death due to mesothelioma was observed. Effects of Smoking Smoking and asbestos exposure are more than additive in their combined ability to increase the risk of lung cancer. Hammond et al. reported results of their 10-year follow-up of 8,220 as bestos insulation workers with known smoking status (38). The mortality experience of these workers was compared with that expected among smokers and nonsmokers of the American Can cer Society's prospective cancer prevention study. Asbestos workers who did not smoke showed ap proximately a fivefold risk of lung cancer com pared to the nonsmoking control population. On the other hand, a more than sixtyfold risk of lung cancer was observed for smoking asbestos work ers compared to nonsmoking controls. A similar multiplicative effect was observed by Selikoff et al. among a factory cohort producing amosite insulation (129). Although less striking, cigarette smoking may also contribute to the risk of death due to asbestosis. Hammond et al. reported that asbestosis death rates of smoking asbestos workers were 2.8 times as high as that of nonsmoking asbestos workers. Meurman found less associa tion between asbestosis mortality and smoking; he reported 7 of 42 asbestosis deaths among non smokers (86). Mortality and Pleural Radiographic Changes The relationship between pleural thicken ing and calcification and subsequent mortality is important insofar as surveillance of asbestos workers is concerned. Edge studied the mortality of 429 shipyard workers with plaques and com pared this to matched controls without plaques (25). Among those with plaques, 23 mesotheli omas were observed and workers with plaques had 2.5 times the lung cancer risk of those with out plaques. Sheers observed 6 mesothelioma deaths among 410 dockyard workers with plaques, but he found just 2 mesotheliomas in those with only pleural fibrosis (130). Neither of these studies established causality between pleural changes and subsequent development of mesothelioma or lung cancer because neither asbestos exposure or latency were controlled for in the analysis. Meurman has shown that anthophyllite asbestos workers have a high prevalence of pleural changes but a minimal mesothelioma risk (86X87). However, plaques and pleural thick ening do indicate an asbestos exposure and this fact alone places the workers at an increased risk for lung cancer and asbestosis. Respiratory Morbidity All types of asbestos have been shown in epidemiologic studies to be associated with as bestosis, pleural thickening, and pleural calcifica tion. Available evidence from cross-sectional and prospective respiratory disease studies provide lit tle evidence that any one type of asbestos is more biologically active than another insofar as x-ray or clinical changes are concerned (149) (164). These findings are fully supported by animal bioassay data. Important epidemiologic studies of respira tory morbidity among asbestos workers are sum marized in Table 11-12. In these studies, various objective measures of effect or disease outcome have been used including chest roentgenographs, spirometry, measures of diffusion capacity, and chest auscultation. Subjective data such as re spiratory symptoms obtained by questionnaire have also been used. In the diagnosis of "definite asbestosis,'* most studies have relied upon com binations of objective and subjective data. Mixed Fiber Exposures Early cross-sectional studies of chest roent genographs of asbestos workers by Merewether and Price, Donnelly, Schull, and Dreessen et al. demonstrated a striking prevalence of pulmonary fibrosis of as much as 80% for workers employed more than 20 years (22)(23)(84)(131). Several studies have been conducted among insulation workers. Selikoff et al. studied chest films of 1,117 insulation workers exposed to chrysotile and amosite (122)(124). A 50% over all prevalence of pulmonary fibrosis was ob served increasing to 90% among those employed more than 30 years. Pleural calcification showed an increasing prevalence with latency reaching 57.9% at 40 years since initial employment. Pleu ral fibrosis (thickening) occurred earlier than calcification. Murphy et al. also studied shipyard insulation workers and found a prevalence of asbestosis 11 times that of age matched, nonexposed controls (92)(93). Exposures among this group were thought to be low. Cross-sectional data from an asbestos textile plant processing a mixture of asbestos types were used by the British Occupational Hygiene Society (BOHS) in establishing occupational exposure standards (8). Among 290 workers employed after dust controls were installed in 1933, only 8 workers (2.7%) demonstrated x-ray changes considered consistent with asbestosis. Basal rales was taken as an early disease marker with a 1% risk estimated for a working lifetime of 50 years at an average exposure of 2 fibers cc. Workers at this same plant were subsequently studied cross-sectionally by Lewinsohn (67). This latter and much larger study demonstrated a signifi cantly greater prevalence of pulmonary fibrosis; reaching 40.5% among workers employed from 30-39 years. Pleural fibrosis (thickening) was observed in 1.6% of those employed 1-9 years and in 50% of workers employed more than 40 years. Berry et al. reported the results of a prospec tive study of workers employed in the same plant studied by Lewinsohn (67). This study consisted of 379 persons completing 10 or more years em ployment by 1971. Possible asbestosis was diag nosed based on one or more combinations of basal rales or crepitations, radiological changes, a falling transfer factor and restrictive lung func tion changes. Among these 379 men, 60 cases of possible asbestosis were diagnosed by the factory medical officer, whereas 85 cases were diagnosed by an independent clinician. Using plant expo sure data, it was estimated that the cumulative dose necessary for a 1% incidence for crepita tions, possible asbestosis, and certified asbesto sis was 43 fiber/cc-yr, 55 fiber/cc-yr, and 72 fiber/cc-yr, respectively. Two cases of certified asbestosis were observed among nonsmokers and nine among ex-smokers, suggesting a contribu tory smoking role. Weiss reported similar find ings in his study of 100 asbestos textile workers where a 24% prevalence of pulmonary fibrosis was observed in nonsmokers versus 40% for smokers (159)(161). Gregor et al. demonstrated a progression of radiological changes in asbes tos workers referred to the British Pneumoconi osis Medical Panel without further asbestos exposures (36). Lung function and chest film effects of ex posure to asbestos cement dust have been studied by Weill et al. (157X158). This study included 859 workers in two asbestos cement plants who were administered respiratory symptom question naires, spirometry, and chest films. Cumulative dust exposures were estimated and expressed as mppcf-yr. Both small rounded and linear opac- Table 11-12 SUM M ARY OF RESPIRATORY M O RBIDITY STUDIES OF ASBESTOS EXPOSED POPULATONS FEVi. Obstructive impairment seen in high exposure group. Few trends in diffusing capacity. co IIS|Is 2 I'f IjE IfE ws 00 U- 4) ACo E sU .2 a ~ CQ >. 3a a g eo 3 .M eco kgCO u gw SE c k CE > & 3 5 X2)*--8 S3 A o.gR E ao c-S " V) E3 > 8. 05 2 Vk 05 . > "A gE -! S b B -O *C Ak BA Is CU C B st _A UB5 .3 05 *"TM 2o 05 -- is ss AA #Cu fqc. O * A X_k) 3s ^ l-- k * S' ? Si A w ^A 62 e ^S 1 X A 5 1 3 sE B2 k = 2 05 05 A *11 2E *- o ~ A A go & o k- O a a E ts h # ___ oo A 3k *5S5 3O o in^ ,9 a. ctt *n g .E 09 05 *53 B O **3 05 o *0 3 -a 05 W O A E > 05 --S33 -k * E A3 X> o sS w x3> w *Ac sJ IB 0o335 Ot w if C/3 Ox -bk: rS- X os S-o B w A 0*5 2 k O ~O B 3 E 05 A C/3 J3 k- o *8 A e - *3> S o OE a 05 J*3S5f 1| o .s2 s O01 k U co A H k Z 2 .C e-s s it a* 2 ._S -1 ko GO -- 2$ 0 C 05 12 8 .2 g -- :g o A U U Xu >&.S oo c < is a B A oi '35 Co x: b UA A B u a B A .3 flu U. SV-J 5 vp t-. ON OE A =g J* k o -- *Ti vO o B 3 g 2 J2 03 A 05 C 0O5 2k rU*7 X oc 2 B .O 'k ss 05 A 0055 BU o2 U^ x o 05 k x: U 2 p *O-k Be R-g A 05 fc Si (rS~ jj k o 05 >. k U 05 k O S3 ^o Pe >*o kB J3 A O 05 Sg i N r-* 2?*o ^S 5E A O t?f O e OX B3 *0 C C/5 A J3 !E 2 o 3 C/5 A A 22 BO a 22 2 CQ 44 Tabic II-12 SUMMARY OF RESPIRATORY M O RBIDITY STUDIES OF ASBESTOS EXPOSED POPULATONS (Continued) in 0-9 years and 50% in 40-49 years exposure group. 3 ... O 4> _3U T33 |I o.o >> > V __ 5o gE 5 *Z is il 3 *- <S| e^ 2 2 > * > wOc CRgA> --a O Oha g e j= 3 X) O * 2 8. S _O I a# 23 Og Ws S-O 2*2 w^ 3 Vo w SS i is * s.,1 & g># 1> *53 5 rft 0 * -ll Jj-"! j* 3 A .Si *-" tu X! -- O ~ 3 *00 g c S3| 3 60 a 25 a Q.S & 6.0 y *1s oe ca -- ca *g.S S> .3 w 18-g * 2 ji **r e>9 .E_ (A h4>a .X 0 3 JJ ^>, O g&* EN e Iff 1g-ss wM C O S .2 c 3 Pa> h. g III O1/1 h <s gWa> -Sft-j 09 ^w 50 "8 34> >. ^w -Es o VN 3" 81 CA ha =# _o -- 2 60 u w S3 C \ 3^2 2 O X)CA 3 h. o> 32 co E * G ^a oCA 2 3# oaCA --NO XV >*3 a> w 3g'2e| AS flj 1g_. ha o ^ ON m 6 Q, ** -2 * sO Os 5; =4eu> U o .e -JJ 55 If " 5* JCur ^o o3- ^a. so. I M 3 o* a >> 9 S 35 <o O s a 3 o c CA o = CA o c CA i`2 C3 73 *2 G ~" s > ovaa. 2 25 3 CA C A ha O a> .2 uo --w ca 3 <OCA cJa> 2 uu w -. CA 3 CA B oA fhj. ha ^3 cj 2 SJ V U flj s. H 5 oha a CM bh >s ha js O CA o CA JS Vw 'i g <N M o0o --3 cb C/5 irt E C 2 rO-' 2 wo iSl > CA 25 <9 (J CA JZ uha *E3 o w = 6 n Ec r ON c $ o c .X c 3 s-g M hi 4c>a >O a S s * " *a ON *u 4o> XX s-g MO 3-- sX <N i OO CA j 2^ XtlA> -hoX. 8* r- ^ 60 'X <N x * %> rrN~ O' <0 73 2 (A IT <9 C Q S C9 o u c X o C/5 X o J4J CQ aJ 45 Table 11-12 SUM M ARY OF RESPIRATORY M O R BID ITY STUDIES OF ASBESTOS EXPOSED POPULATONS (Continued) a 53 2 .-w 3o > 5uO S& 8*2 . <2 O B " k. 3 p 52 _ HI * w A >. > * Oca a *t>5> g| :a o| o fmr B k ^1> ia_> fO>c d ^M c00 cB 5 o OS 3 fcO >> AU ."*G2 --cE *csa .*3- O ow Ce *3; Oca M (A A 0Es9 SO A ca JC> 2 -- k. O CA A A <*- i- A 3B EX k. rg .sK -o I sA 60 5><s cA B Eg - o .u ol U% vs 3 E (A k- B3 Su gS -g i> .2 6 A- "3 t> 2 Q. sggS -as. o5 s= *8 ] "5J MAT} R Q.V Us. >w Vx x.ti > Ofil! u- a -- cM "t ^2 60 22 cc --b8(J o3 B'TJ . i Jf3.s #*n #---- On W> O > BUm WM A o*B SffA (A .2 Q. >. 3 *0 A <A <O .3 w 5 Ow O 60*3 3 rr ^ 8S *3 2. g eu .3 V3 32 <A A, oa. ^ X4> 4A ao o (A V J= 1 60 JJ r *r ^2 E ^ a. 3 2 u> 8 09 CA 12 B3 2 G Vca a (A C Mo k fV*7> Xt> o3 CA if .2 ov 8 -- ^A Ji B O *>(A I-- r" m r*T X U 4J a2 B -2 3 o8 V ___ A ca C o oCA k. S- 3 u .* & H a 4> X e MO * so 82 Os 5 09 n wS On r & ON *8 X o (A -X 2O Xc) * %g 8oo i S -*> r O' V X V ca *X 2o S X) w MC9 B^ os E oon Du 1^1 r On Te3 A 2 *Sa 2I u1 60 O A^ CA .2 1 S oS OO k. 2 o oa oo r On A r ?> o >. k. k. CQ 46 aA ou X H 3A w 4> A w4J C A *C *5 Table IM 2 SUMMARY OF RESPIRATORY M O R BID ITY STUDIES OF ASBESTOS EXPOSED POPULATONS (Continued) duced in association with dust and fiber exposures. w0a0 IeS s> a> 20O0 O3OU-. J2 2 w. 00 3 c^ o^ Ere ^c A 2 w ] o^ oo '35 33 re . 32 o re v) is 1! 0J S 0 Ij . =< c_ - g-8 11 # m sz 3 s `/j oo 3 * sos s S 9 ^ re oeg=c of-- ig c/5 ^2 u > llGI3 -- -So i/i >> -= TCr3e V .3 * .2 oo T3 .3 re 00 > 3 Oac/5 ^ v.. " S s g> re t & 5u -Ji .so^ -- j= . 5/5 o 23 > 3re alx is u. re X) co 1OC. "> 0*5 Q. 3 C flj TT33 ooo a CU T3 X V 3re 3 E 3 c/5 23 c 32 O O cre xc oo .E *re 11 ft. .2 cre o re o" E oaX o Q. # >,no O3 oo __ o re 5^ oil : ^3 * g S .12 i f 8 i su ;; ^o oe =2 cE>t I W -- ,0 X i: = #Oon-"Ss--OO2caEou1/d5 _"^-rcOa3VC>e> 2X--tOEocrr^3tf>ee)-l -= 3o rae re x " c .r>o2e V) ?3reP I | ! i i i 1 1 :i S U ai u r* .*5 1 ` g-o 2 - E w Ja-gre >UJ sin_ SC g-8 a E </5 o c _o o E ^3 1/5 E -- ` v^5 r>e 2g aE 3 o S' a o B c *5 ' 2 Q 11 >99> --^ 05 oAt/i cV* fU'T X sa . NO 2 a ss 2: oo re --. s --re o i-g 8f V re SE 2r uu c 1 oC/5 ] : i w re re a = 2 E O ,, 3 __ -- 1 !t i1 ^ !V/>5 OL. 2 E x re 3 , o ! U c. Va S' O T03> X *croe j= C.J3 O E OO 3S E < <2 T3 C9 S, TS9 V) e ri ^ 05 OO 3 TT E t-~ ro~s- Q 0> w 2o t X) ,, 5S e sI <N Orn On Cd ^ 1l ? 2 >N 52 IJ S'o OrN On c g3 ^ -2 2E --<N T33 -- re OrN ON re o .x 05 !Dco%ur.> u. 8 S co < 3re *eD O re 47 Table 11-12 SUM M ARY OF RESPIRATORY M O R BID ITY STUDIES OF ASBESTOS EXPOSED POPULATONS (Continued) 00 e9 s r slfe mfr llS *8gs si O >* --- 00 g Ou_ _--a> *>oo> k. E .o _ 2a ---c E * <a C CO m Jis Es >> a 2a t? .2 <N 8.S -* g -- c 2 c -a <2 . 112 o' * *5.2 *~ i3 # g v> j es a a S^: 5. mm aa.. * 2 s > 5*^ 15 l=l aE S O. O^ 2 iis s s s 2 &1 > ovi c _ C. *C! * - j- k- O JS cc O C^ 2e?--^ ko. 2 .(2 *" *2 ouoo Oku. oge cue CACs Ow * Oe b0 2a C<0 as k--a a m .3 00 O -- ka & l " . kJ .3 W a " c a . v -- .e > a o. t IA. oo E 2 ca ocJg m M fc a a c r_S 00 .^2 2 a o . o3*S s3ooc 2 *aoo gig t-gs m (m sa a** 3 ft> o iO2: i3 tS co k. Cl CQ. a c fiS fc *o-j= f S Cw ooS k. 3s a--> 2 g > k. 8 .*2 S <oA Oo. aEw 5- ^ A > flu E < o c "ceod c o ao M *co 35 CA c IA ka o X oa. 3O. 4 O. (A > .ill CA k. O. o. (A A aa aa i= a U2 E X eao H 1- E !2 uo 2E u< 6 ei a <eo0 4to= t/i ae Pu I! 2 2 oo rs: fc co - ES s Or-s Os o *s (>A% X o o sill 2o $3 * E S | s - o1! E -s 22 Ors Os a >. Em IA A ^8.-S73I Cg *us oW S *> <rt >k.>*C-a2* <>k3a. Os rOs is 21 l O. ^ J 15 o " ijt -->c ooo -- u 00 r* r** Os Os CO tti X tS 60 5 48 aa a-a wO00 ka o .15 a O OS a > a& ka a ities were observed, indicating the possible role of small quantities of silica present in cement dust. Among those with a cumulative exposure less than 50 mppcf-yr, and approximately 4% prevalence of small opacities (rounded or irreg ular, profusion >1/0 was observed; the preva lence of these changes increased to 30% with an exposure of more than 400 mppcf-yr. Pleural changes were seen in 11% of those in the lowest exposure category. Both FVC and FEV, were reduced in those with x-ray changes. There was no apparent interaction effect of cigarette smok ing on the development of diffuse fibrosis. Jones et al. studied the progression of radio graphic abnormalities and lung function changes among 204 asbestos cement workers between 1970 and 1976 (48). Films'were read side by side in known order and ranked according to progres sion. These authors concluded that: (1) progres sion of small opacities depended upon both ave rage and cumulative exposure; (2) declines in lung function were related to both smoking and cum ulative exposure; and (3) pleural abnormalities progressed as a function of time. Disease inci dence was not estimated in relation to exposure. Anthophyllite and Tremolite Respiratory morbidity among Finnish an thophyllite miners and millers has been studied by Meurman et al. (87). Among 787 active em ployees, a threefold excess of dyspnea and a two fold excess of cough was observed among asbes tos workers compared to controls. The prevalence of dyspnea was not found to be associated with smoking habits. A high prevalence of pleural plaques has been reported among persons residing near an thophyllite mines and mills in Finland (51)(85). In two mining communities where mass roent genological surveys were conducted, prevalences of pleural plaques of 9% and 6.5% were ob served compared to less than 0.1% for the Fin nish population. Talc deposits found in upper New York State contain both anthophyllite and tremolite. Workers in talc mines and mills in this area have been shown to experience pulmonary fibrosis, pleural changes, and restrictive lung function changes (52)(54-57)(107)(132)(133). A recent cross-sectional study of lung function and chest x-rays among talc workers in this area was reported by Gamble et al. (31). Compared with coal and potash miners, talc miners and millers were found to have an increased prevalence of cough and dyspnea along with reduced FEV,, FVC, and flow rates. Talc workers with more than 15 years employment were found to have a 33% prevalence of pleural calcification and pleural thickening. Recent exposures in these operations were reported by Dement and Zumwalde (19). Time-weighted-average fiber ex posures were found to range from 0.8 to 16.0 fibers/cc with 12-19% identified as tremolite and 38-45% anthophyllite. Chrysotile--Radiological changes, lung function, and respiratory symptoms among Canadian chrysotile miners and millers have been extensively studied by McDonald et al. (76) (77) and Becklakeet al. (4). A total of 1,015 cur rent employees were given chest x-rays, under went pulmonary function studies, and were ad ministered a standard British Medical Research Council Questionnaire on respiratory symptoms. Both persistent cough and phlegm (bronchitis) and breathlessness on exercise were found to in crease with exposure. The prevalence of bron chitis rose to 50% among smokers in the highest dust exposure categories. The prevalence of breathlessness was not affected by smoking but rose to greater than 40% in those with cumu lative dust exposures over 800 mppcf-years. The prevalence of irregular small opacities (>l/0 ILO/UC) in the lowest exposure category was found to be 1.8% for the Thetford mine and 6.4% for the Asbestos mine. Prevalences in creased to 26.4% for Thetford and 10.9% for Asbestos in the group with exposures more than 800 mppcf-yr. The prevalence of pleural thick ening was found to be less strongly related to exposure. Among various lung function pa rameters measured, both FVC and FEV, de clined more with exposure. Those with small opacities of category 2/1 or greater were found to have significantly reduced functional residual capacity, residual volume, and single breath dif fusing capacity at rest. Only FVC and FEV, were reduced in those with earliest roentgenographic changes. Cross-sectional respiratory disease studies have been conducted among chrysotile miners and millers in Newfoundland and Corsica (7) (121). Selikoff studied 485 current employees of a chrysotile mine in New foundland and found a 5% prevalence of parenchymal abnormalities (1LO U/C >\/0) (121). This prevalence increased to 11.5% among those employed more than 10 years. The prevalence of pleural changes was less than that observed for parenchymal changes. Boutin et al. studied chest films of 16 ex workers of chrysotile mines and mills in Corsica which had been closed in 1965 (7). Compared with controls, chrysotile miners and millers had 2.4 times the risk of parenchymal abnormalities and 2 times the risk of pleural abnormalities. Ex posure levels among those workers were extreme ly high, ranging from 85 to 267 mppcf. The above studies of chrysotile asbestos workers have been cross-sectional by design and have likely underestimated risks since: (1) those who develop severe disease are likely to have al ready left employment, and (2) chest film changes may develop after termination of employment, or changes may be progressive without additional exposure. Liddell et al. studied chest film changes in a 20-year longitudinal study of chrysotile miners and millers (62). These authors observed a 20-year cumulative incidence for small irregular opacities of 16%, a pleural calcification incidence of 5.3%, and a pleural thickening incidence of 5.3%. Only the incidence of small opacities was strongly associated with smoking. Rubino et al. studied the progression of chest film changes among retired chrysotile asbestos miners and millers and found that 39% of those who had initial films with a profusion of 1/0 or greater, demonstrated progression without further ex posure (116). Becklake et al. also studied radio logical changes after withdrawal from asbestos exposure (5). Parenchymal progression was ob served in 7% of the films, pleural progression in 19.8%, and both parenchymal and pleural pro gression in 2.3%. These changes were found to be independent of age and smoking, but paren chymal "attacks" occurred more among those with higher asbestos exposure prior to employ ment termination. Relationships between radiological findings and subsequent mortality among chrysotile miners and millers have been studied by Liddell and McDonald (69). This study consisted of 4,559 whose latest film had been read according to the UICC/Cincinnati classification system with mortality follow-up from time of film as sessment through 1975. Overall, this cohort ex perience significantly increased mortality for all causes (SMR = 144), lung cancer (SMR = 177), pneumoconiosis (31 cases), other respiratory diseases (SMR = 127), diseases of the heart (SMR = 136), cancer of the esophagus or stom ach (SMR = 170), and cerebrovascular diseases. There were 5 pneumoconiosis deaths among those classified as having normal radiographs; however, the risk of death due to pneumoconiosis was 11.75 times greater among those with "lessthan-normal" films. The lung cancer relative risk for those with chest film changes was 3.24 and most who died of lung cancer were found to be smokers. Small parenchymal opacities were pre sent in most but not all persons whose deaths were attributed to lung cancer. The authors concluded that the chest radiograph was useful for surveillance of asbestos workers but was limited due to radiological progression after withdrawal from exposure and by the carcino genic risk associated with dust retained in the lung. PATHOLOGY Pleural Plaques Hyaline plaques of the parietal pleura oc cur in association with exposure to all commer cial types of asbestos. They are more common than the pulmonary parenchymal lesions of asbestosis, thus their presence does not necessarily imply coexistent asbestosis. The majority occur in men, 20 years or more after first exposure. The plaques almost invariably involve the parietal pleura; less commonly they are found on the visceral pleura or parietal pericardium. They are usually bilaterally symmetrical and appear as well circumscribed, pearly white or creamy, fibrotic elevations of the pleura (Figure 11-11). Their sur face is smooth and glistening with either a flat, plateau-like or nodular contour. They range in size from a few millimeters to several centimeters in diameter. Most commonly they are found following the lines of the lower ribs posteriorly or on the diaphragm. On cut section, they have the consistency of cartilage. Histologically, the plaques are composed of avascular and acellular bundles of hyalinized collagen arranged in a reticulated mesh or "basket weave" pattern (Figure 11-12). Some of the more nodular plaques show a whorled pattern of collagen fibers. Focal calcification is fairly common and elastic fibers are sometimes demonstrable within the plaque (112). Although the plaques are almost acellular, lymphocytes and plasma cells may be present around blood vessels beneath the plaque. The origin of the plaque is not known; histological studies suggest an extrapleural rather than a pleural origin (145). Asbestos bodies are rarely seen in pleural plaques, though they can usually be detected in the underlying pulmonary paren chyma (40)(112). Short, uncoated fibers may be present in a proportion of plaques (40) (65). Pleural plaques rarely, if ever, undergo malignant change. Asbestosis In early or mild cases of asbestosis, the lungs may be of normal size and shape; in advanced cases, they show a marked reduction in volume. The visceral pleura is usually pale, opaque, and thickened, particularly over the lower lobes. Adhesions between the visceral and parietal pleura may be present. In the absence of other exposures, pleural pigmentation is usually slight. The lungs may appear grossly normal in cases showing histological evidence of mild dis ease. However, on careful palpation, it is usual ly possible to detect an increased firmness of the parenchyma. With advancing disease, the lungs are dark tan in color and show a pale reticular fibrosis. Characteristically, the fibrosis is most prominent in the lower lobes and dependent pans of the upper and middle lobes. In the late stages of the disease, the lungs have firm, spongy tex ture and show dense fibrosis with areas of cyst formation (honeycombing). The honeycomb Figure 11-11. Diaphragmatic pleura of 68-year-old ex-construction worker. Numerous dome shaped and flattened, ivory colored plaques are seen over both hemidiaphragms. 51 Figure 11-12. Histological section off pleural plaque. The plaque is composed off acellular bundles of collagen fibers arranged in a "basket weave" pattern. Hematoxylin and eosin x 64. cysts vary in size from a few millimeters to a centimeter or more in diameter and are most prominent in the lower lobes and subpleural areas of the lungs (Figure 11-13, A & B). Emphysema is unusual and, when present, is not related to asbestos exposure. Massive fibrosis is a less com mon feature of asbestosis and probably results from mixed dust exposure. Necrotic nodules similar to Caplan's lesions in coal workers have been described in patients with asbestosis and circulating rheumatoid factor (91). Microscopically, the earliest lesion attribut able to asbestos inhalation involves the respira tory bronchiole. Fibers deposited on the wails of respiratory bronchioles and adjacent alveoli stimulate a macrophage response. Depending on fiber size, giant cells may form. The macrophagic response is followed by the deposition of reticulin and collagen in the walls of the respira tory bronchioles (Figure 11-14). Asbestos bodies and fibers are found in association with the le sions of the respiratory bronchioles and within alveoli. A similar lesion has been described in cigarette smokers (100). The early lesion of as bestosis differs from the respiratory bronchiol itis of cigarette smokers only with respect to the presence of asbestos bodies. The diagnosis, therefore, of asbestosis depends upon the recog nition of asbestos bodies within the lesion. As the disease evolves, the fibrosis extends out to involve the walls of adjacent alveoli. Even tually, adjacent acini are affected resulting in a diffuse interstitial fibrosis (Figure 11-15). With further progression of the disease, the pulmonary architecture becomes distorted. Intra-alveolar fibrosis leads to obliteration of alveolar spaces 52 Figure 11-13 (A). Freeze dried whole lung section from Si-year-old male plumber exposed to asbestos lag ging for 16 years. There is marked honeycombing of the mid and lower zones. and eventually to areas of conglomerate fibrosis (Figure 11-16). Despite the obliteration of alveolar spaces, the outline of the walls of the alveoli usually remain intact and can be demonstrated with elastic stains (138). Eventually, fibrouswalled (honeycomb) cysts form (Figure U-17). The cysts are lined by flattened or metaplastic epithelial cells of ciliated cuboidai, goblet, or squamous type. These changes are nonspecific and may occur in the late stages of pulmonary fibrosis, whatever the etiology. This pathogenetic sequence of events forms the basis for a grading system developed by a committee of U.S. pulmo nary pathologists assembled under the auspices of the National Institute for Occupational Safety and Health and the College of American Path ologists (16). The above features appear to be common to all the commercially available types of asbes tos. Several other types of tissue response have been described in association with asbestosis. These include chronic inflammatory cell infil trates, desquamative interstitial pneumonia (15), and the formation of intra-epithelial eosinophilic hyaline bodies (62). These features are not spe cific for asbestos. Asbestos Bodies and Fibers Two types of fibers are encountered in the lungs; uncoated fibers that resemble the inhaled particle and coated fibers or asbestos bodies. The ratio of uncoated fibers to coated bodies is high, ranging from 5:1 to 10,000:1 (10). Asbestos bodies are an index of asbestos ex posure and are considered an essential feature for the histological diagnosis of asbestosis (16). They may be formed in the lungs as early as two months after first exposure (135). Asbestos bodies tend to form on the larger fibers, \., those greater than 5pm in length and result from the deposition of iron-protein complexes on the core fiber by alveolar macrophages (143). In hematox ylin and eosin stained sections they appear as golden brown segmented structures with a clear central core fiber. In Perl's iron stained sections they appear blue. The morphology of the coating is variable, with club-shaped or beaded bodies predominating (Figure 11-18). Similar structures may form around other minerals such as carbon, ceramic aluminum silicate fibers, and fiberglass, and they have been termed ferruginous bodies (37X42). They usually lack the clear central core of a typical asbestos body. These types of bodies are relatively uncommon, however, and for prac tical purposes, it can be assumed that a typical asbestos body contains an asbestos fiber. Al though all major commercial types of asbestos can produce asbestos bodies, the majority of the core fibers, when analyzed by selected area elec tron diffraction, are found to be amphibole asbestos (11). Several procedures exist for the quantification and identification of fibers in tissues (11)(16X137)(150). The majority of these fibers are too small (<5 pm in length) to be Figure 11-13 (B). Roentgenogram showing marked interstitial disease with honeycombing which is most severe in the mid zones. resolved by the light microscope. Electron micro scopical studies on selected cases have shown that occupationally exposed workers have pulmonary asbestos fiber counts orders of magnitude greater than the general population (16)(163). The value of these techniques is to establish exposure and to identify the mineral type and should not be considered a substitute for more conventional diagnostic methods. Currently, the role of the short fibers in the pathogenesis of asbestosis and asbestos-associated lung cancer has not been resolved. Lung Cancer The association between asbestos exposure, smoking, and lung cancer is now firmly estab lished. The majority of asbestos-associated bron chial carcinomas arise in lungs that also show asbestosis. Autopsy and mortality studies in dicate that th<* prevalence of lung cancer in per sons with asbestosis ranges from 12-55% (42) (136). The lung cancers associated with asbestos exposure occur at a slightly earlier age than in nonexposed individuals (74). They arise in rela tion to the fibrotic lesions and are thus more common in the periphery of the lower lobes (49)(162). All histological types of cancer occur with most (41)(42)(162), but not all (49), studies 54 Figure 11-14. Section of lung from 68-year-old asbestos insulation worker showing the histological features of mild asbestosis. The lesion is characterized by peribronchiolar fibrosis in which there are numerous asbestos bodies. Inset shows an asbestos body. Hematoxylin and eosin x 100. Figure IM4 (Inset). 55