Document 0q47QjpBje9J0xDoQ0YV23gOk

docline https://docline.gov/docline/requests/receipt/receipt.cfin7Progr3j2l 'All lAOSft BILL JUN 2 2 2009 Request # 27288694 Ariel To: 192.68.30.164 Houston Academy of Medicine-Texas Medical Center Library Photocopy/InterLibrary Loan Services 1133 John Freeman Blvd Houston, TX 77030-2809 JUN 19,2009 DOCLINE: Journal Copy EFTS Participant Title: Title Abbrev: Citation: Article: Author: NLM Unique ID: PubMed UI: ISSN: Publisher: Copyright: Authorization: Need By: Maximum Cost: Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondaztone clinic Monaldi Arch Chest Dis 1998 Apr;53(2): 168-80 Asbestos in the lungs of persons exposed in the US Langer AM;Nolan RP 9307314 Verify: PubMed 9689804 1122-0643 (Print) Fondazione Clinica Del Lavoro Edizioni, Pavia Copyright Compliance Guidelines sonia! N/A $100.00 Patron Name: Referral Reason: Library Groups: Phone: Fax: Email: Yana Posey TN: 197733 Not owned (title) SCAMeL 1.713.799-7179 1.713.790-7056 tmcariel@exch.library.tmc.edu Comments: Prefer ariel delivery... 192.68.30.164.... EFTS participant Routing Reason: Routed to CAUCLA in Serial Routing - cell 3 Received: Lender: Jun 19, 2009 ( 08:20 PM EST) University of California, Los Angeles/ Los Angeles/ CA USA (CAUCLA) This material may be protected by copyright law (TITLE 17,U.S. CODE) Bill to: TXUTEX Houston Academy of Medicine-Texas Medical Center Library Photocopy/InterLibrary Loan Services 1133 John Freeman Blvd Houston, TX 77030-2809 10 of 15 6/19/2009 5:20 PM Monaldi Arch Chest Dis 1998; 53: 2, 168-180 PROCEEDINGS Asbestos in the lungs of persons exposed in the USA A.M. Langer, R.P. Nolan ABSTRACT: Asbestos in the lungs of persons exposed in the USA. A.M. Langer, R.P. Nolan. Tissues obtained at autopsy or biopsy from 81 work ers and 2 household persons, were chemically digested. The asbestos fibres recovered were characterized by analytical transmission electron microscopy. Among the 83 causes of death were 33 mesotheliomas, 35 lung cancers, 12 asbestosis and 3 from other cancers. Of the three major commercial asbestos fibre types, amosite was found to be the most prevalent fibre, occur ring in ~76% of the cases, followed by chrysotile in -60% and crocidolite in -24%. Amosite and chrysotile were observed as the single commercial fibre in -22 and -17% of the cases respectively, whereas crocidolite and tremolite were found as the single fibre type in only -2.5% of the cases. Among the fifteen cases where chrysotile and tremo lite occurred together, the amount of chrysotile fibre always exceeded tremolite. However, tremolite was also found in ten additional cases where chrysotile was not detected. Amo site was present in four, amosite plus crocidolite in three, and crocidolite alone in one. Amosite was present in all of the insulation workers' lungs studied and was found in the highest concentration in this exposure category. The highest chrysotile concen tration was found among workers in general trades. Although most prevalent in shipyard workers lungs, crocidolite con centration is not statistically different among the exposure groups studied. Although crocidolite was found in twenty cases, amosite accompanied it in eighteen of these. Eleven of the 20 cases were from shipyard workers. Of the 8 mesothelioma cases, 7 also contained amosite. Crocidolite alone only occurred in 1 of the 33 mesothelioma cases analysed. We concluded the following: crocidolite exposure occurred among USA insulators and a large percentage of other workers as well; insulation workers are primarily ex posed to amosite; mixed fibre exposures are associated with more mesotheliomas than single fibre exposures; chrysotile only exposure is associated with -12% of the mesothelioma cases studied; and if tremolite exposure is associated with chrysotile exposure, the chrysotile amount exceeds that for the associated tremolite. Monaldi Arch Chest Dis 1998; 53: 2, 168-180. Keywords: Asbestos, asbestos diseases, exposure, tissues. Environmental Sciences Laboratory, Brooklyn College of the City University of New York, New York, USA. Correspondence: A.M. Langer, Environmental Sciences Laboratory, Brooklyn, New York 11210, USA. Studies to determine the types, concentration and morphology of asbestos fibre retained in human lung tissue by analytical transmission electron microscopy (TEM) are important in understanding the aetiology of asbestos-related disease. This is especially so in situations where asbestos-related disease occurs, but the nature of the past exposure is uncertain. Such information has been sought for decades [1], Recently, the limitations of lung content analy sis for asbestos have been viewed negatively not so much for the information gathered but rather for the lack of agreement between epidemiological claims and the results of lung content analysis that appar ently refute them [2]. This is especially so for the asbestos fibre type associated with mesothelioma. For example, the 1976 study by Pooley [3] of Can adian chrysotile miners and millers raised the issue that tremolite (an amphibole mineral sometimes asso ciated with chrysotile asbestos ores) was an addi tional agent in the induction of asbestosis. Later, this was expanded to include mesothelioma [4], Despite all of the criticisms, analysis of the fibres found in lung tissues are critical to understanding the aetiol ogy of asbestos-related disease. Current postulates concerning asbestos and disease There exist in the USA important claims con cerning asbestos exposure and asbestos-related dis ease which lung content analysis can help resolve. Consider the following six postulates: The mortality experience ofinsulation workers can not be related to crocidolite exposure. Outside of the asbestos cement industry, how extensive has croci dolite usage been in the USA? It has been claimed that crocidolite was not imported into the USA much prior to 1930, and it was not used in insulation prod ucts. Therefore, USA insulators were not exposed to it before 1930 [5] (see also Appendix). During the Second World War, US warships used amosite only and military shipyard workers at this time, unlike those in the UK, were either minimally or entirely unexposed to crocidolite. Using these claims an argu ment concludes that chrysotile may be the agent res ponsible for the majority of mesotheliomas observed in pre-1930 exposed American insulation and ship yard workers, especially those whose exposures began before the widespread introduction of amosite around ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA 1930. Therefore, the pre- and post-1930 mesothe'!oma experience of the insulation workers, which Ji much the same, is chrysotile-related. These asser tions have influenced the regulatory policy in the USA on fibre type and diseases [6]. Is this claim re garding crocidolite usage in the USA supported or refuted by lung content analysis and crocidolite con sumption information? All the asbestos fibre types induce mesothelioma equally well. The US Department of Labor's Occu pational Safety and Health Administration in its most recent asbestos standard, still does not distinguish among the asbestos fibre types in terms of mesothe lioma risk [7], This position stands in opposition to that taken by 14 other industrial countries which per mit different workplace exposure levels for the dif ferent asbestos fibre types [8], Crocidolite's permissible exposure level is frequently one-tenth the value for chrysotile. The relationship between asbestos fibre type and mesothelioma is frequently couched in subtle seman tics, as reflected by several recent papers in the USA literature and exchanges they provoked [9, 10]. This exchange focused on the importance of fibre type in producing mesothelioma rather than relative fibre potency. A less potent fibre may produce more tumours in a population because it is more widely used. Chrysotile was therefore deemed more dange rous than crocidolite. Which fibres types are present in the lungs of workers dying with mesothelioma? Chrysotile exposure alone does not cause human mesothelioma. Some investigators claim that chrysotile alone cannot cause pleural and peritoneal mesothe lioma at any dose. Are there any cases of mesothe lioma in which only chrysotile can be found in the lung? Chrysotile exposure is invariably associated with tremolite exposure. In addition to crocidolite, tremolite has been the focus of several studies in the fibre carcinogenesis field. It has long been known that inhalation of tremolite asbestos is associated with human mesothelioma [11], Tremolite was reported in the lungs of chrysotile-exposed miners and millers in Thetford, Quebec [3,12], Tremolite has been found in greater concentration than chrysotile in the lungs of forty Thetford cases [13], Results of epidemiolog ical studies suggest that the lung cancer and mesothe lioma experience of chrysotile-exposed workers are so varied that perhaps tremolite played a role [14], Tremolite form, asbestos fibre or cleavage fragment, is yet another issue as is the presence of other nonamphibole fibrous minerals, for example, diopside. This claim has been carried into end-product indus tries and industries which receive and process chrysotile fibre from sources outside of the Thetford area. If chrysotile exposure is associated with mesothelioma or lung cancer, and chrysotile alone is weakly or nonmesotheliomagenic, then the logical conclusion must be that the associated tremolite, which may accom pany the chrysotile, is the aetiological agent in these diseases. Are these assertions supported by lung con tent studies? Exposure to mixtures offibres is more dangerous than exposure to a single type. The fibre synergy hypothesis was proposed almost 20 yrs ago in an attempt to explain and correlate mesothelioma mor tality with lung content studies [15]. Many more me sotheliomas occurred in workers in the UK whose lungs contained more than one fibre type as opposed to lungs which contained only one. One American investigator insisted that his fibre consumption data reflected chrysotile exposure in the American insu lation workers before 1930 and to chrysotile-amosite mixtures after 1930, resulting in a very similar meso thelioma proportional mortality experience. The hy pothesis was abandoned largely because the experience of the American insulation workers was thought not to fit the pattern. After all, chrysotile fibre is found in pleural tiss ues, and more mesotheliomas are found in cohorts exposed to both amphibole fibres and chrysotile [15, 16]. What do the fibre data show? Product type and work environment controls the nature ofexposure, dose and disease. The fibre types and amounts found in American workers' lungs in large measures reflect the products used and the nat ure of the work environment where the products were manipulated [17]. That is, the insulation trades tended to be exposed both to amphibole- and chrysotile-containing products, and their work was often confined to cramped and poorly ventilated areas so that high concentrations of mixed asbestos dust were generated and subsequently inhaled. Therefore can dose explain, at least in part, the high incidence of asbestos-related disease among insulation workers? In summary, do lung content studies (fibre types, amounts and their character) support or refute these six postulates? Material and methods Almost exclusively, pulmonary tissues were re ferred to our laboratory through consultation. For each case asbestos exposure was established on the basis of occupational and/or personal history. The questions asked were often not if exposure to asbestos dust occurred, but rather to which fibre types and concentrations? Further, did these reflect the work ing environment and was there any correlation with a specific disease? The selection was clearly biased toward cases with occupational exposure and asbestosrelated diseases. The underlying questions was always: "What is in this lung?" The tissues were obtained at either autopsy or biopsy, and sent for verification of diagnosis and quantitation of asbestos lung content. The majority were formalin-fixed bulk tissues although some were mounted in paraffin blocks. The 83 tissues examined represent 81 persons occupationally exposed to asbestos in the work place, and 2 persons thought to have been exposed in a domiciliary setting (table 1). A control group for these specimens was not collected during the period of analysis. The specim ens were collected over many years. No case came with a control specimen. Limitations existed for the development of a control group retrospectively. Rather, A.M. LANGER, R.P. NOLAN Table 1. - Information provided with the tissue specimens examines Exposure category Category 1 Insulator/ pipe coverer Category 2 Shipyard worker Category 3 Other trades Category 4 Family members Total n=83 Males n=80 Females n=3 Age data n=64 Average age yrs Range Trades identified 23 23 0 13 60.97.2 54-74 Insulator (21) Pipcoverer (2) 28 28 0 27 60.99.5 45-78 Electrician (3) Welder (2) Machinist (2) Shipfitter (2) Pipefitter (2) Labourer (1) Sheetmetal (1) Sailmaker (1) Seafarer (1) Chipper and caulker (1) Shipyard (12) 30 29 1 24 56.59.3* 31-68 Construction (5) Railroad (3) Plasterer (3) Brake repair (2) Pipefitter (2) Plumber (2)' Electrician (1) Welder (1) Labourer (1) Sheetmetal (1) Maintenance (1) Rubber (1) Undercoater autos (1) Other traders (6) 2 0 2 0 65+ Housewife (2) The average age for all patients was 59.39.2 yrs, range 31-78 yrs. Data for "Trades identified" are presented as numbers in parentheses. *: the ages of "other trades" are younger than the persons making up the other exposure cat egories (p<0.05 by t-test); +: age available for one housewife only. results were compared with lung content analysis data collected among persons who died in the general population of New York City, during 1966-1968, the years of maximum asbestos consumption in the USA [18, 19]. These persons had no known occupational asbestos exposure and did not die of any asbestosrelated disease. None of the 83 cases reported here had a lung content analysis comparable to anyone in the general population. Information provided for each case The information which accompanied each tis sue specimen varied in detail. The most complete in cluded the person's name, age, sex, occupational history, years in a specific trade(s), clinical history, primary cause of death (if deceased), secondary or contributing causes of death, e.g., asbestosis, in lung cancer or mesothelioma, and notation of tobacco and alcohol consumption. Complete data were available for only 63 of the 83 cases studied. Twelve of the 28 shipyard cases were noted as shipyard worker, rather than by specific trade, such as an electrician, in a shipyard. Incomplete data sets are noted (tables 1 and 2). Exposure categories After review of the data provided and prelimi nary analysis of 83 tissues received, it became ap parent that three major exposure categories existed. Category 1: insulation workers and pipecoverers. Specimens obtained from twenty three individuals had occupational histories of either insulation work or pipe covering (table 1). Occasionally, the occupa tional history of the insulation worker noted work in other dusty trades. Insulation and pipecovering tra des involved exposure to thermal system products. Only one insulation worker and one pipe coverer had exposure in a shipyard, insufficient to generate a se parate exposure category. They were included as part Table 2. - Distribution of asbestos-related diseases among the exposure categories studied Diseases* , Category 1 Insulator/ pipe coverer n=23 Category 2 Shipyard worker n=28 Category 3 Other trades n=30 Category 4 Family members n=2 Total of groups n=83 Mesothelioma Lung cancer Asbestosis+ Other cancers 9 (39.1)ns 8 (34.8)ns 6 (26.1)** 0 (0.0) 12 (42.9)ns 12 (42.9)ns 2 (7.1)** 2 (7.1) 12 (40.0)ns 13 (43.3)ns 4 (13.3)ns 1 (3.4) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 33 (39.76) 35 (42.17) 12 (14.46) 3 (3.61) Data are presented as number within the category and percentages with that category in parenthesis. *: ascertainment by clinical information, occupational histories, and review of pathology materials. +: asbestosis as a cause of death. Asbestosis was also noted as present in 5/33 mesothelioma cases, 9/35 lung cancers, 1/3 other cancers. Total of all asbestosis, 27/83 cases or 32.5%. Note 85.5% malignancies among the cases, ns: percentage of mesothelioma and lung cancer among exposure categories 1, 2, 3, not significantly different. **: p<0.01, percentage of asbestosis deaths among categories 1 and 2 are statistically different. n i a i ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA of category 1 exposure. Category 2: shipyard work ers. Specimens obtained from 28 individuals com prise this group (table 1). Any worker noted as having an exposure component which included a shipyard environment, who was not an insulation worker or pipe coverer, was included in this category. Duration of shipyard work was not a factor in exposure clas sification. For example, in table 1, three electricians are included as shipyard workers because their indi vidual occupational histories indicated employment in this setting. Category 3: other trades and family members. Specimens obtained from 30 individuals comprise this group (table 1). If a worker had no ex perience as an insulator or pipe coverer and never worked in a shipyard environment, the individual was placed in this category. Only 2 of the 83 cases were nonoccupationally exposed and for exposure comparisons they are grouped with other trades (cate gory 3). Tissue preparation Lung parenchyma specimens were obtained from individuals who developed mesothelioma, lung can cer, asbestosis and other cancers (table 2). Weighed aliquots of formalin fixed bulk tissues (~l-5 g) were completely digested with 5% potassium hydroxide [20], A hot water bath, set at ~95C, accelerated the reaction, which was invariably complete after ~6 h. Tissues impregnated in paraffin tended to be sma ller in size, some as small as 20 mg. This has not been considered an obstacle in that successful analy sis of small specimens obtained by transbronchial lung biopsies, has been reported [21]. These were subjected to xylene and ethanol baths to dissolve and remove the paraffin. The recovered specimen was washed in distilled water, weighed and subjected to alkali digestion following the above protocol. It has been reported that some paraffin blocks may be contaminated with short chrysotile (<1 pm) fibres [22], However, the origin of the fibre was un known, and the issue raised was one which called for the use of control blocks. In this study only fibers >1 pm in length were counted and thereby avoided this confounder. The chemical digestates were cen trifuged at 10,000xg and resuspended in distilled water 5-8 times. This technique is similar to that used for lung content analysis of exposed persons in the general population [18, 19]. A 10 pL aliquot taken from a 10 mL final dis persed KOH-cleared suspension, was micropipetted onto carbon-coated formvar support, nickel locator grid. Four to six such grid preparations were made and allowed to dry. After drying, the grids were ex amined by TEM to insure particle distribution homo geneity and integrity of the substrate. The dust residue was examined by analytical electron microscopy. The three diagnostics required for identification of fibres were morphology, structural characteristics determined by selected area electron diffraction, and chemical characterization by energy dispersive spec troscopy [23], Lung content analysis Mineral residues were examined over a range of magnifications, from 600-50,OOOx on the TEM view ing screen. Fibre counts were made at 10,000-20,OOOx magnification on the TEM screen by systematic xy traverses. Fibres were noted on a morphological basis and a preliminary separation of chrysotile and amphibole was made. It must be noted that some fibres were too thick, thereby preventing transmis sion of diffracted electrons, even when the beam was accelerated at 100 kV. Representative thin fibres had their selected area electron diffraction patterns pho tographed and the plates were analysed to verify the presence of an amphibole or chrysotile structure. Common Laue zone patterns for the amphibole asbestos minerals were used for identification [24--26]. Specific amphibole species were determined by chem ical characterization using energy dispersive X-ray spectrometry. Each spectrum obtained was compared with standards for identification. Fibres were enumerated and counted on at least 10 grid openings, and based on the area of the prepa ration scanned, fibre number was calculated and expressed as millions of fibres-g-1 of wet tissue. For data presentation, the values are expressed as fibresg'1 of dry lung tissue (10 g wet tissue is equivalent to 1 g dry). Fibre concentration values are expressed as those >1 pm in length present in 1 g of dry lung tissue. The fibre length limitation applied in counting was instituted to avoid incorporating background chrysotile into the final chrysotile count. This ubiq uitous object, a single chrysotile fibril with an aver age length of about <1.0 pm, is commonly found in the lungs of persons who die in New York City [18, 19] with no known exposure to asbestos, especially in the occupational setting. The chrysotile values given here are therefore biased towards exposures which are point source in origin. This also holds, but to lesser degree, for the amphibole asbestos min erals. The limits of detection ranged from -10,000 100,000 fibres-g1 dry lung tissue. The 1 pm length limit has been embraced by others for similar rea sons [27], Variance is necessarily associated with indivi dual fibre counts. Under ideal conditions of assay, it is related to the actual concentration of fibres pre sent in the specimen and their distribution on the prepared grids. However, it is also related to the amount of tissue digested, from where in the lung the specimen was obtained and preparation proto col. Fibre count in the present study was carried out on at least 10 grid openings, the values obtained were averaged, and the scatter about the mean calculated. As the number of fibres increased, the spread around the mean decreased. An interesting discussion of the problems in interpreting the results of lung content analysis (both random and systematic errors) is in the literature [2], Most of the error sources were well known in the analytical community [28,29] and some of these have been recently discussed [30]. The concentration of fibres >1 pm in length (fib res-g-1 of dry lung tissue), ranged considerably. All the data sets contained high or low value outliers which generated arithmetic averages with large stan dard deviations. Therefore, all statistical comparisons are made on the basis of geometric means (GM) and geometric mean standard deviations (GS) which gre atly reduce the effects of outliers. t A.M. LANGER, R.P. NOLAN Results Fibre types found in the 83 cases Amosite, chrysotile and crocidolite fibres, the major commercially used asbestos fibres, either sin gularly or in combination, were recovered from all but 2 of the 83 parenchymal tissues studied (table 3). Amosite was the most prevalent fibre found, oc curring in -76% of the tissues examined, followed closely by chrysotile, found in -60%. Crocidolite was quantified in 23% of the cases (table 3). In one tis sue specimen a single crocidolite fibre was found and it was noted as present, raising its prevalence to 24%. Greater amounts of chrysotile were found than either amosite or crocidolite (p<0.01) and greater am ounts of amosite than crocidolite (p<0.01). This quanj titative trend reflects the general fibre consumption figures over the past eight decades. However, rather than a chrysotile to amphibole tonnage consumption ratio of 19:1, the data indicate only a -2.6:1 lung con tent ratio, favouring chrysotile. The role that chrysotile degradation and/or elimination played in this find ing is unknown. Both amosite and chrysotile asbestos were found as the single asbestos fibre type in 39% of the tis sues, as compared to crocidolite which occurred alone in only two of the tissues studied (table 3 and 4). Tremolite-actinolite (primarily tremolite with some ferrotremolite) and anthophyllite were also found in the tissues studied, with tremolite-actinolite occur ring more frequently (in -30% of the tissues stud ied) and twice as the only fibre type detected (tables 3, 5 and 6). When both tremolite and chrysotile oc curred in the same tissue (in 12 cases where tremo lite was quantified) chrysotile concentration always exceeded tremolite (table 5). Tremolite was found in 10 cases without chrysotile. but was associated with amosite and/or crocidolite in 8 of these (table 6). Anthophyllite was found in -33% of the cases studied although it never occurred as the single fibre type detected and it was quanti fied in only half the cases. Fibre types and concentration by exposure cate gory Among the insulation workers (category 1), all of the cases had amosite recovered from their lung tissues (table 7) and in some, crocidolite was also found. Similar findings have been reported by oth ers [31, 32], The latter report found crocidolite in 7 of the 13 cases examined, at concentrations slightly higher than those reported here. Amosite concentra tion ranged over almost three orders of magnitude. Amosite occurred with highest concentrations in cat egory 1 as compared to those in the other two expo sure categories (p<0.001). The next highest amosite concentration was found among the category 3 ex posure workers. Chrysotile was found in 12 and crocidolite was found in 3 of 23 cases in category 1 (table 7). Table 3. - Presence and concentrations of fibre types found in lung tissues of the 83 cases Fibre type Cases n Cases % Fibre concentration 106xfibres-g_1 dry lung tissue* GM Range Cases with one fibre type n Cases % Lone fibre cases fibre observed % Amosite 63 75.9* 7.56.5 0.2-350 18 21.7 18/63 (28.6) Crociodolite 20+ 24.fi 2.75.6 0.1-89 2 2.4 2/19 (10.5) Chrysotile 50 60.2* 26.329.5 0.1-7790 14 16.8 14/50 (28.0) Tremolite- 25# 30.1 6.0+6.5 0.1-177 2 2.4 2/25 (8.0) actinolite Anthophyllite 27$ ' 32.5 3.44.4 0.1-50 0 0.0 0/27 (0.0) Amphibole only, 22/83 (26.5%); chrysotile only, 14/83 (17.0%). cm: geometric mean. *: fibres>lpm; +: 19 of 20 cases report quantities, 1 case single fibre found (present) and quantities based on 19 cases; #: 21 of 25 cases report quantities, 4 cases sin gle fibre found (present) (see table 6) and quantities based on 21 cases; : 14 of 27 cases report quantities, 13 cases single fibre found (present) and quantities based on 14 cases; *: significant difference between percentage occurrence of crocidolite and amosite (p<0.02), crocidolite and chrysotile (p<0.01). Crocidolite is less prevalent. . Table 4. - Asbestos-related diseases and concentration where a single commercial asbestos fibre type is detected Lone fibre found Mesothelioma Lung cancer Asbestosis Amosite gm+sd Range Cases n Chrysotile gm+sd Range Cases n Crocidolite Cases n Total cases n (%) 5.86.1 0.2-34.8 6 125.67.2 11.0-770.0 4 3.0 1 11 (36.4) 7.1+5.3 0.6-110.0 10 87.551.8 0.1-5440 8 7.0 1 19 (54.3) 40.6+1.5 30.0-55.0 2 338.834.9 140-820 2 0 4 (33.3) gm: geometric mean. For amosite: asbestosis > mesothelioma (p=0.02-0.05); asbestosis > lung cancer (p=0.05); and mesothelioma - lung cancer (ns). For chrysotile: asbestosis > mesothe lioma (p<0.001); asbestosis > lung cancer (p<0.01); and mesothelioma > lung cancer (p<0.01). ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA Table 5. - Tremolite and chrysotile in pulmonary tissues in quantifiable concentrations Chrysotile Tremolite 106xfibres-g-1 dry lung tissue Job description Cause of death Other fibres 1344.0 1340.0 820.0 610.0 366.0 301.0 280.0 220.0 15,0 7.0 7.0 1.0 0.7 0.2 0.1 33.128.6 14.0 14.0 2.0 20.0 50.0 177.0 60.0 4.0 1.4 2.0 0.6 0.5 Present Present Present 7.06.7 House painter/ plasterer Plasterer Plasterer Shipyard Shipyard Shipyard Insulator Engineer Shipyard Insulator Insulator Shipyard Shipyard Shipyard (machinist) Shipyard (electrician) Lung cancer Lung cancer Asbestosis Asbestosis Lung cancer Lung cancer + asbestosis Mesothelioma Lung cancer + asbestosis Mesothelioma + asbestosis Lung cancer Mesothelioma Lung cancer Mesothelioma Mesothelioma Mesothelioma BLD BLD BLD Amos, Croc Amos, Croc Amos, Croc Amos BLD Amos Amos Amos, Croc Amos Amos Amos BLD BLD: below level of detection; Amos: amosite; Croc: crocidolite. Chrysotile: tremolite ratio range 410:1 to 2:1, quantitative val ues (n=12), arithmetric mean ratio -12:1 and geometric mean ratio -4.7:1. Table 6. - Tremolite presence with chrysotile below limit of detection Tremolite Amosite Crocidolite Disease Job description 94.0 69.7 12.0* 7.0 3.0 1.9 1.8 1.0 0.3 Present* gm 4.96.7 HK'xfibre g*1 dry lung _ 34.8 '- 22.0 5.8 0.6 15.8 0.4 0.2 gm 3.28.4 _ 7.0 3.0 1.3 3.4 gm 3.1 2,0 Asbestosis Mesothelioma/asbestosis Mesothelioma Lung cancer Mesothelioma Lung cancer Lung cancer Lung cancer/asbestosis Mesothelioma Mesothelioma Construction worker Insulator Housewife** Housewife Railroad worker Pipecoverer Shipyard worker Maintenance worker Electrician/powerplant Welder gm: geometric mean; *: presence of anthophyllite also (600,000 fibres-g*1 dry lung tissue). **: Occupation of husband unavailable; +: noted as present, (one fibre detected). Table 7. - Fibre type, concentration* by category of exposure (trade) Trade Amosite Crocidolite Chrysotile Tremoliteactinolite Anthophyllite Category 1 Insulator/ pipe coverer (n=23) Category 2 Shipyard worker (n=28) Category 3 Other trades household (n=32) GM Range % GM Range % GM Range % 15.6+4.7 0.8-320.0 100 3.46.9 0.2-91.0 75.0 6.67.1 0.2-350.0 59.4 1.6+3.7 0.6-7.0 13 2.58.2 0.1-89.0 39.3 4.22.5 1.3-14.0 15.6 13.7+30.1 0.8-5400.0 52.2 16.821.9 0.1-7790.0 67.9 76.024.0 0.4-5440.0 62.5 22.7 0.6-70.0 26.1 28.0 0.1-177.0 32.1 23.3 ; 1.0-94.0 31.3 9.8 1.0-44.0 21.7 13.0 0.3-50.0 21.4 4.3 1.0-12.0 12.5 gm: geometric mean. *: concentration of fibres are given in I06xfibres-g*1 of dry lung tissue; fibres >1 pm length. A large proportion of shipyard workers (categ ory 2) also had amosite (-75%) and chrysotile (-68%) recovered from their lung tissue, but crocidolite (-39%) occurred with greater frequency than in the other two exposure categories (table 7). However, the con centrations found among the exposure categories were statistically indistinguishable (p>0.05). The other trades (category 3) also had amosite and chrysotile recovered from lung tissues, and some crocidolite as well. The amount of chrysotile was greatest in cat egory 3 exposure, with about equal amounts found among cases in the other two categories (table 7). The category 3 group contained tissues from three railroad workers. Amosite fibre was found in two (22xl06 and 55xl06 fibres-g1 dry lung tissue), and crocidolite in one of these (3x106 fibres-g1 dry lung tissue). The mixed amphibole exposure occurred in a person with mesothelioma. The chrysotile-only exposure hypothesis for all railroad workers [33] is not supported by these findings. A.M. LANGER, R.P. NOLAN Amosite concentration ranged over almost three 10-fold difference (table 3). If 99% of the chrysotile orders of magnitude. The concentration of chrysotile, and 80% of the crocidolite inhaled during life was greatest in the category 3 exposed workers, ranged eliminated, back-calculation yields an almost 200 over almost five orders of magnitude (tables 3, 4 fold differential in the original inhaled average dose and 7). The tissues obtained from shipyard workers of these two fibre types: 2,600x10A chrysotile to (category 2) tended to have lower concentrations of about 14xl06crocidolite, deposited in a volume of amosite and chrysotile as compared to those found tissue corresponding to the 1 g of dry lung tissue. in insulation workers and workers in other trades Time since cessation of exposure is an important (category 3). unknown variable among the cases. However it seems unlikely that the high chrysotile fibre concentrations were determined only in recently retired or current Fibre types, concentrations and asbestos-related ly employed workers, as opposed to those determi diseases by exposure category nations made for crocidolite. Values for different fibre types obtained on single lung specimens support this Among the insulation workers studied, asbest- conclusion. Use of lung content analysis in the res osis is cited more frequently as a cause of death as olution of the original postulates raised take these compared to the other exposure categories (table 2). processes into consideration. Quantitation of expos Fibre concentrations in insulation workers' lungs indi ure based on retained fibre number is a relative index. cate that only their amosite exposure was more inten se than that experienced by workers engaged in other trades or workers in the shipyard environments (table j Examination of the six postulates 7). . . Workers in all exposure categories had virtua ' The mortality experience of American insulation lly the same mesothelioma mortality. However, these workers cannot be related to crocidolite exposure. cases were selected from a nonrandom sample of Crocidolite has been found in the lungs of about persons known to have been occupationally exposed 24% of the American workers studied and is more to asbestos (table 2). prevalent in the lungs of shipyard workers (tables 7, Four of 33 mesotheliomas (-12%) occurred in 8). Crocidolite was found in 39% of the tissue spec individuals whose lungs contained chrysotile asbestos imens obtained from individuals who had some his as the major commercial fibre type (table 4). It has tory of shipyard work (table 7). Five tissue samples been reported in Germany that 72 of 843 mesothe with crocidolite were obtained from a railroad work liomas (-8.5%) had occurred in workers whose lung er, an undercoater of automobiles, an electrician, the content analysis found only chrysotile [27], wife of an insulator, and a maintenance worker (table The concentration of amosite alone, and chrysotile 8). A trace of crocidolite was found in the tissue of alone, was greater in those with asbestosis, than in a construction worker. Crocidolite is also present in those with mesothelioma (p<0.01). The chrysotile- the lungs of 13% of the insulation workers studi only mesothelioma cases contain very high fibre con ed (table 7). It is important to note that amosite centrations (table 4). Twenty-two mesotheliomas accompanied crocidolite in -90% of the cases where are associated with mixed-fibre exposures and eleven crocidolite was found (table 8). This suggests that with exposure to single fibre type exposures. High exposure to these fibre types covaried as the result concentrations of uncoated fibres in the lungs of per of either specific products or work sites. Its distrib sons with asbestosis has been reported previously, ution among the exposure categories suggests it was and a general correlation was found between degree widely used. of scarring and fibre concentration [34, 35], Langer and Nolan [17] found that for American insulation workers, amosite was universally present Discussion while crocidolite occurred less commonly in their pulmonary tissues. In all studies, higher prevalence of the amphibole minerals was observed than would Lung content analysis for mineral fibre is of the be anticipated by USA commercial consumption fig residual fibre population. The long, durable fibres ures. For example, crocidolite was found in 39% of are preferentially retained while both short and non shipyard workers when only 1-2% of the total asbestos durable fibres are removed. However, many of the consumed in the USA was this fibre type. lungs examined in this study indicate the presence Selikoff [36] commented during a discussion of very high concentrations of chrysotile, on a fibre that crocidolite-containing cigarette filters [37] may number basis, as compared to the amphibole fibres have been the source of crocidolite fibre found in present in the same tissue specimen. Chrysotile is, the lungs of insulation workers reported by Kohyama in some instances, biopersistent [19, 36]. This would and Suzuki [32]. The data now available suggest that mean, (if the elimination data are in principle cor this speculation was unwarranted. The historical con rect and exposure variables are normalized), that ex sumption data of Selikoff [37] are not accurate (see traordinarily greater amounts of chrysotile would Appendix) and ample opportunity existed for many have been inhaled during the lifetimes of these wor American workers to be exposre to crocidolite. Further, kers. Compare the concentrations of chrysotile and crocidolite filters in Kent cigarettes were introduced crocidolite as shown, for example, in table 3. The in 1952 and accounted for a total of -110 metric geometric mean chrysotile content of the lungs stud tonnes consumption between 1952-1956 [38]. This ied is -26x106 fibres-g'1 of dry lung tissue as com was only a small percentage of the total yearly cro pared to ~2.7xl06 fibres-g-1 for crocidolite, about a cidolite consumption (-20 metric tonnes-annum 1 as ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA Table 8. - Crocidolite and other fibres, in pulmonary tissues of 20 workers Crocidolite Amosite Chrysotile Job description Cause of death 106xfibres-g1dry lung tissue 88.5 50.0 20.0 14.0 7.0 3.4 3.0 3.0 3.0 2.0 1.3 1.0 1.0 0.7 0.7 0.6 0.6 0.4 0.1 TR 90.5 50.0 65.0 1.0 21.0 0.4 22.0 BLD 1.0 5.0 15.8 30.0 1.0 14.0 BLD 12.0 16.8 1.5 0.2 4.5 301 366 610 BLD BLD BLD BLD BLD BLD 2.0 TR 0.3 BLD BLD BLD 7.0 1.5 BLD BLD BLD Shipyard (welder) Shipyard Shipyard Undercoat autos Insulator Electrician Railroad Shipyard Shipyard Shipyard Maintenance Insulator Shipyard Shipyard (machinist) Wife (insulator) Insulator Shipyard (electrician) Shipyard Shipyard Construction Lung cancer + asbestosis Lung cancer Asbestosis Lung cancer Asbestosis Mesothelioma Mesothelioma Mesothelioma Mesothelioma GI cancer Lung cancer + asbestosis Asbestosis Mesothelioma Mesothelioma Lung cancer Mesothelioma Mesothelioma Lung cancer Lung cancer Lung cancer Geometric mean (sd) for crocidolite 2.45.6, amosite 6.76.6 and ehrysotile 17.122.4. BLD: below level of detection; GI: gas trointestinal; TR: trace or one fibre detected. Nineteen cases were those in which crociodolite was quantifiable, 18/20 cases asso ciated with amosite (90%), and 8/20 cases, associated with ehrysotile (40%). compared to -8,000 metric tonnes-annurrr1 of cro cidolite consumed in other applications). It is noteworthy that both insulation and ship yard workers were exposed to amphibole-containing and mixed-fibre products. In the former instance, insulator contact was with amosite fibre and, to a lesser degree, depending on time, crocidolite. For ship yard workers, many trades worked in this environ ment. Fibre exposure was, in part, bystander in character with attendant lower quantitative total ex posure (table 5). The first postulate, that crocidolite exposure cat egorically did not occur, especially among insula tors, is rejected on the basis of lung content analysis. Whether or not some or even all of the early meso thelioma deaths reported among insulators were cro cidolite induced, is unknown. For workers exposed after 1930, the answer is known: yes, some were ex posed to crocidolite; and all were exposed to amosite. All the asbestos fibre types induce mesothelioma equally well. The data generated in this study sug gest that the mixed fibre types are associated with more mesotheliomas (n=22) than exposure to any of the three commercial fibers alone (n=ll). Among the mesothelioma cases amosite and ehrysotile occur more frequently than crocidolite. Chrysotile exposure alone does not cause human mesothelioma. Compare the data for the different fibre types, in table 4, where concentrations for sin gle asbestos fibre types, by asbestos disease, are given. The amosite and chrysotile exposed populations com prised of almost an equal number of cases (18 and 14 respectively). For mesothelioma, -22 times more chrysotile fibres, on average, are present than amosite. The geometric mean value of ~126xl06 fibres-g-1 of dry lung tissue of chrysotile compared to the 6x106 fibres-g-1 of dry lung tissue for amosite. This diffe rential is similar to that in studies of chrysotile-exposed workers who succumbed with mesothelioma [39], If these numbers are qualitative indices of expo sure and the fibre population represents retained dose, a worker must inhale many orders of magnitude more chrysotile fibre, as compared to amphibole fibre, to achieve the same risk for mesothelioma. The single asbestos fibre type in the mesothelioma cases pro vides further evidence that chrysotile occurs without tremolite, and at very high doses can produce pleu ral mesothelioma [36]. Chrysotile exposure is invariably associated with tremolite exposure. Unlike earlier reports of chrysotile miners and millers, in this series of cases when chrysotile and tremolite were found together in the same lung specimen, chrysotile content always exceed ed tremolite. Only in 2 of 83 cases was tremolite the only asbestos fibre type detected. The lung con tent analysis obtained on 94 miners and millers from the Thetford area of Quebec indicated an opposite relationship. Exposure to these ores, some known to contain tremolite, may not reflect a general pattern for all persons who are chrysotile exposed. Based on our data, the tremolite claim does not hold for all chrysotile exposures [14, 35]. Rather, tremolite occurs with highest concen trations in the lungs of plasterers (table 5). Patching, taping and spackling compounds marketed in the USA are known to have contained tremolitic talc in addition to chrysotile. This may be a source for tre molite but these materials have been shown to con tain cleavage fragments rather than asbestos [11]. In seven individuals who succumbed with mesothelio ma, amosite and/or crocidolite was found in six. Five of the seven involved shipyard work and the others involved insulation work (table 6). In seven of nine cases where tremolite was found without chrysotile, amosite and/or crocidolite was also present. In four A.M. LANGER, R.P. NOLAN cases where tremolite was found as trace, three con tained amosite. Of the total 25 cases (11 with mesothe lioma) where tremolite was found, nine contained amosite and/or crocidolite. Chrysotile exposure may be associated with tre molite exposure. However, when tremolite is found without chrysotile present, it is generally associated with other types commercial amphibole asbestos. Calcic-amphibole contamination of amosite needs to be considered as well as other sources of tremolite unrelated to chrysotile. Exposure to mixtures of asbestos fibres is more dangerous than exposure to a single type. These data allow re-examination of risk following expo sure to mixed-fibres as compared with the risk fol lowing exposure to the commercial asbestos minerals alone. Mesothelioma occurred in four cases where chrysotile was the only asbestos fibre found, as com pared to seven cases where only a single amphibole asbestos fibre type was found. Mixed-fibre popula tions were associated with 22 of the 33 mesothelio mas. These numbers only roughly approximate the multiplicative model postulated by Acheson and Gardner [15] (22~7 x 4). Product type and work environment control the nature of exposure, dose and disease. The majo rity of the mesotheliomas (22), occurred in persons whose work environment provided opportunities for intense as well as mixed-fibre exposure. An obser vation which mitigates against dose as a controlling factor (e.g., insulation workers are exposed to high concentrations of dust) is that the two commercial amphibole fibres are present in lowest concentrations in individuals with mesothelioma. The data also indi cate that chrysotile alone may induce mesothelioma in humans, but the fibre exposure required is much higher than that associated with exposure to amosite and crocidolite. If chrysotile consumption was 19 fold greater than that of amphiboles asbestos during the past three-quarters of a century, why are chrysotileonly mesotheliomas not more common? The ques tion is not so much whether or not chrysotile is mesotheliomagenic but rather how potent is it? The data indicate that it is not as potent an agent as, for instance, crocidolite on a fibre-for-fibre basis. Conclusion The pulmonary tissues of a group of asbestosexposed persons in the USA, who died of asbestosrelated diseases, were examined. Amosite was observed with the greatest frequency, followed by chrysotile, anthophyllite, tremolite-actinolite and crocidolite. In terms of concentrations, as indexed by fibre number, chrysotile was the most abundant fibre found, follo wed by amosite, tremolite-actinolite, anthophyllite and crocidolite. The frequency and exposure category occurrence of the amphibole asbestos varieties amosite and cro cidolite suggest that specific products, e.g., pipe insu lation containing amphibole fibres, used by specific trades, and work environments, to a large degree ex plain the disease pattern. The frequency of occurr ence and concentration data are so skewed from USA consumption figures, that the usefulness of the lat ter in gauging exposure is questionable. For exam- pie, crocidolite consumption in the USA tended to average only about 1-2% of the total fibre used in commerce over many decades. However, it was found to be present in the lung tissues of 24% of all workers and -39% of shipyard workers. A similar distribution holds for amosite. For American insulators, the presence of amosite is ~30-fold greater than is indicated by consumption figures. Amphibole expo sure among shipyard and insulation workers has been noted previously [13]; risk of peritoneal mesothelioma is thought to be especially increased follow- ing exposure to amosite [40], The Rochdale studies which focus on mesothe- lioma are frequently said to reflect gross fibre con sumption figures, i.e., 98% chrysotile, 2% crocidolite exposure [41]. However, a small portion of the Roch dale works was engaged in manipulating crocidolite only. The lung content found was consistent with the known exposure to chrysotile although crocidolite was also present at a concentration 300-fold higher than that of the general UK population [42]. Again, in such an example, usage of consumption figures are limited, perhaps even misleading, as exposure surrogates. This argument, on ratios of fibre types, has been used periodically by the investigators to support the contention that the commercial asbestos fibre types have about equal mesotheliomagenic potential. A recent review in the USA accepted the consumption data at face value, which led to the same erroneous conclusion: chrysotile produces as much malignant disease as the amphiboles [43], Some amosite pipe lagging was made with calcined diatomaceous earth and magnesia. Manipulation of such a product generates a complex aerosol. The role that crystalline silica and particulates <2.5 pm in diameter in lung fibrosis in insulation workers remains unclear. Such components of the workplace aerosol may be associated with the small, rounded opacities which frequently accompany irregular scar patterns in asbestosis. There may be many explanations for the high concentrations chrysotile observed in tissues: firstly, there is greater opportunity for chrysotile exposure because more of the fibre was used; secondly, as chrysotile fibre bundles disaggregate, the number of individual fibrils may actually increase with time of tissue residence, leading to a higher exposure in dex; thirdly, chrysotile possesses some biopersis tence; and lastly, the mineral recovery process may produce an increase in fibre number as an artifact of preparation. Fibres >5 pm in length found in this study constituted from -5-50% of the fibre populations mea sured. Unfortunately, such data are of limited value here. The great range of tissue masses examined, lack of information concerning location of speci men in terms of anatomical site, and the problems associated with number of fibres counted introduces uncertainty [28, 44--46]. There appears to be more long fibres in these tissues than have been reported in bulk samples when the latter are examined by transmission electron microscopy [36]. Based on the j l | ; ( ? j ' / [ | [ ? | / ' ( , j j ? j ' ( x ( " 1 | ... ' X > ( >J v,t ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA data in the present study, the ability to unequivo cally distinguish between the effects of dose and fibre length was not possible. Considering the shortfibre elimination bias, it may never be possible. Acknowledgements : The authors express gratitude and thanks to colleagues who gave so generously with time, advice, mate rials, and critical review: M. Ross of the United States Geological Survey; R. Wilson, Dept of Physics, Harvard University. We also note the assistance of A. Bentsianoff who provided assis tance in the statistical analysis of data. The authors thank N. Svoyskaya for preparation of the manuscript. References 1. Selikoff IJ, Churg J. - Biological effects of asbestos. Ann NY Acad Sci 1965; 132: 720-721. 2. Baker DB. - Limitations in drawing etiologic infer ences based on measurement of asbestos fibers from lung tissues. Ann NY Acad Sci 1991; 643: 61-70. 3. Pooley FD. - An examination of the fibrous mineral content of asbestos lung tissue from the Canadian chrysotile mining industry. Env Res 1976; 12: 281-298. 4. Churg A. - Chrysotile, tremolite and malignant mesothe lioma in man. Chest 1980; 93: 621-628. 5. Selikoff IJ, Hammond EC, Seidman H. - Cancer risk of insulation workers in the United States. In: Bogovski P, Gilson JC, Timbell V, Wagner JC, eds. Biological Effects of Asbestos. Lyon, France, IARC-WHO, 1973; pp. 209-216. 6. Selikoff IJ. - Statement on the proposed asbestos stan dard. OSHA-DOL. Env Sci Lab Report 1984. 7. Federal Register. - 29CFRParts 1910.1001; 1926.1101. 59, No. 153, Wed. Aug. 10, 1994. 8. International Programme on Chemical Safety. Environmen tal Health Criteria 53. - Asbestos and other natural mineral fibers. Geneva, WHO, 1986. 9. Hughes JM, Weill H. - Potency versus importance in fiber pathogenicity. Am J Ind Med 1994; 25: 609-610. 10. Roggli VL, Pratt PC, Brody AR. - Fiber potency vs. importance. Am J Ind Med 1994; 25: 611-612. 11. Nolan RP, Langer AM, Oechsle GW, Addison J, Colflesh DE. - Association of tremolite habit with biological potential: preliminary report. In: Brown RC, Hoskin JA, Johnson NF, eds. Mechanisms of Fiber Carcinogenesis. New York, Plenum Press, 1991; pp. 231-251. 12. Churg A, Wiggs B, DePaoli L, Kampe B, Stevens B. Lung asbestos content in chrysotile workers with meso thelioma. Am Rev Respir Dis 1984; 130: 1042-1045. 13. Churg A. - Pathologic reaction to chrysotile and their mineralogic correlates. Accompl Oncology 1987; 1: 54--58. 14. McDonald JC, McDonald AD. - Chrysotile, tremolite and carcinogenicity. Ann Occup Hyg 1997; 41: 699-705. 15. Acheson ED, Gardner MJ. - Mesothelioma and expo sure to mixtures of chrysotile and amphibole asbestos. Arch Env Health 1979; 34: 240-242. 16. McDonald JC, McDonald AD. - The epidemiology of mesothelioma in historic content. Eur Respir J 1997; 9: 1932-1942. 17. Langer AM, Nolan RP. - Fiber type and burden in par enchymal tissues of workers occupationally exposed to asbestos in the United States. In: Bignon J, Peto J, Saracci R, eds. Non-Occupational Exposure to Mineral Fibers, Lyon, IARC-WHO, 1989; pp. 330-335. 18. Langer AM, Selikoff IJ, Sastre A. - Chrysotile asbestos in the lungs of persons in New York City. Arch Env Health 1971; 22: pp. 348-361. 19. Langer AM, Nolan RP. - Chrysotile biopersistence in the lungs of persons in the general population and expos ed workers. Env Health Perspect 1994; 102: 235-239. 20. Langer AM, McCaughey WET. - Mesothelioma in a brake repair worker. Lancet 1982; ii: 1101 -- 1103. 21. Kohyama N, Kymo H, Yokoyama K, Sera Y. - Evaluation of low-level exposure by transbronchial lung biopsy with analytical electron microscopy. J Electron Microscop 1993; 42: 315-327. 22. Lee RJ, Florida RG, Stewart IM. - Asbestos contam ination in paraffin tissue blocks. Arch Path Lab Med 1995; 119: 528-532. 23. Langer AM, Pooley FD. - Identification of single asbestos fibres in human tissues. In: Bogovski P, Gilson JC, Timbrell V, Wagner JC, eds. Biological Effects As-bestos. Lyon, IARC-WHO, 1973; pp. 119 -125. 24. Champness PE, Cliff G, Lorimer GW. - The identifi cation of asbestos. J Microscop 1976; 108: 213-225. 25. Nord GL. - State-of-the-art of the analytical transmis sion electron microscope. In: Russell PA, Hutchings AE, eds. Electron Microscopy and X-ray Applications. Ann Arbor Sci 1978; pp. 133-147. 26. Lally JS, Lee RJ. - Computer indexing of electron dif fraction patterns including the effect of lattice symme try. In: Russell PA, Hutchings AE, eds. Electron Microscopy and X-ray Applications. Ann Arbor Sci 1978; pp. 169-188. 27. Friedrichs KH, Brockmann M, Fischer M, Wick G. Electron microscopy analysis of mineral fibers in human lung tissue. Am J Ind Med 1992; 22: 49-58. 28. Churg A, Wood P. - Observations on the distribution of asbestos fibers in human lungs. Env Res 1983; 31: 374-380. 29. Gylseth B, Baunan RH, Overaae L. - Analysis of fibers in human lung tissue. Br J Ind Med 1982; 39: 191-195. 30. Becklake M, Case BW. - Fiber burden and asbestosrelated lung disease: Determinants of dose-response rela tionships. Am J Respir Crit Care Med 1994; 150: 1488-1492. 31. Suzuki Y, Kohyama N. - Translocation of inhaled asbestos fibers from the lung to other tissues. Am J Ind Med 1991; 19: 701-704. 32. Kohyana N, Suzuki Y. - Analysis of asbestos fibers in lung parenchyma, pleural plaques and mesothelioma tis sues of North American insulation workers. Ann NY Acad Sci 1991; 643: 27-52. 33. Mancuso TF. - Response to CG Ohlson. Letter to the Editor. Am J Ind Med 1989; 15: 353-356. 34. Churg A. - Fiber counting and analysis in the diagno sis of asbestos-related disease. Hum Pathol 1982; 13: 381-392. 35. Churg A, Wright JL, Vedal S. - Fiber burden and pat terns of asbestos-related disease in chrysotile miners and millers. Am Rev Respir Dis 1993; 148: 25-31. 36. Nolan RP, Langer AM, Addison J. - Lung content ana lysis of cases occupationally exposed to chrysotile asbestos. Env Health Perspect 1994; 102: 245-250. 37. Selikoff IJ. - Discussion, Part 2. Ann NY Acad Sci 1991; 643: 71-73. 38. Longo WE, Rigler MW, Slade J. - Crocidolite asbestos fibers in smoke from original Kent cigarettes. Cancer Res 1995; 55: 2232-2235. 39. Churg A, Wright JL. - Fiber content of lung in amphi bole- and chrysotile-induced mesothelioma: implications for environmental exposure. In: Bignon J, Peto J, Saracci R, eds. Non-Occupational Exposure to Mineral Fibers. Lyon, IARC-WHO, 1989; pp. 314-318. 40. Health Effects Institute-Asbestos Research. Asbestos in Public and Commercial Buildings. Cambridge, MA, HEIAR, 1991; pp. 6-19. 41. Doll R, Peto J. - Asbestos. Effects on health of expo sure to asbestos. Health & Safety Comm. London, HMSO, 1985; pp. 58. 42. Wagner JC, Berry G, Pooley FD. - Mesothelioma and asbestos type in asbestos textile workers: a study of lung contents. Br Med J 1982; 285: 603-605. 43. Huncharek M. - Asbestos and cancer: epidemiological A.M. LANGER, R.P. NOLAN and public health controversies. Cancer Invest 1994; 12(2): 214-222. 44. Dodson RF, Greenberg SD, Williams MG, Corn CJ, O'Sullivan MF, Flurst GA. - Asbestos content in lungs of occupationally and non-occupationally exposed indi viduals. JAMA 1984; 254: 68-75. 45. Dodson RF, Williams MG, O'Sullivan MF, Corn CJ, Greenberg SD, Hurst GA. - A comparison of the feruginous body and uncoated fiber content in the lungs of former asbestos workers. Am Rev Respir Dis 1985; 132: 143-147. 46. Dodson RF, Hurst GA, Williams MG, Corn CJ, Greenberg SD. - Comparison of light and electron microscopy for defining occupational asbestos exposure in transbronchial lung biopsies. Chest 1988; 94: 366-370. Appendix on crocidolite consumption information Crocidolite usage in the USA In the 1960's, when data were yet to be gath ered concerning mortality experience of working co horts exposed to only one fibre type, the position of many investigators, especially those in the USA, was that all varieties of asbestos possessed virtually the same ability to produce disease. In a presentation at the International Pneumoconi osis Conference held in Johannesburg in 1969, the i mesothelioma mortality experienced among North American insulation workers was reported. Although these workers experienced high mortality from me sothelioma, their exposure history was unknown. Selikoff [1]. speculated that for a century earlier, scant information was available on the composition of USA insulation products. However, he went on to state: "Until 1930 chrysotile was almost the entire fibre used, amosite making its appearance later and crocidolite practically not at all." "This is not to say that it can be proven that crocidolite was never used before 1930 for insulation in the USA. Rather, if any were so utilized, it could only have been in very small amounts. Therefore, crocidolite exposure of American insulation workers before 1930 and pro bably before 1940 is unlikely to have occurred to ; any significant extent, and is still a very minor affair." Crocidolite was widely used outside the USA for insulation and lagging [2], and the emerging South African experience dramatically underscored the importance of crocidolite as a mesotheliomagenic : fibre [3,4], The qualifiers of Selikoff [1] were noted and data were presented concerning mesothelioma mortality among the American insulation workers: 22 mesotheliomas occurred among 373 deaths (-5.9%), 2 prior to 1954 and 20 between 1954 and 1968. Clin ical latencies calculated from onset of exposure sug gested important exposures occurred before 1930, earlier than the time period the authors had reason to believe that crocidolite or amosite, was introduced into commerce. Sixteen of 22 mesotheliomas were peritoneal and therefore amphibole fibre was susp ected by many to be the aetiological agent. The issue regarding inclusion of crocidolite into insulation was again discussed in a paper published three years later [5], Presumably based on the same evidence as presented in his 1970 paper, Selikoff [5] now stated the following: "Crocidolite was not used for insulation work in the USA during the peri od covered by our study. Thus, exposure to this fibre cannot explain the cancer risk observed." These arguments were repeated so often that they gradually became accepted by members of the Am erican community. At an international meeting on asbestos diseases held in Johannesburg in 1977, McDonald [6] stated "... (it) is fairly clear that insu lators in North America had not been exposed to crocidolite." Occasionally studies of fibre exposure in trades other than those involving insulation application and removal are used for discussion. A good example of this involved machinists in steam locomotive repair yards [7, 8]. Mancuso [8] stated in his 1988 paper (as underscored by the title of that paper, "Relative risk of mesothelioma among railroad machinists exposed to chrysotile") that during the time period of hire and principal exposure of his mesothelioma cases (1920-1929), the lagging used for steam loco motive: "... was almost exclusively, if not solely chry sotile". "Exposure occurred to amosite or crocidolite as packing or other material... would have been com paratively limited in nature and scope." The more circumspect statements concerning exposures are not reflected in this article title nor in its text. The author further buttressed his fibre type argument with the same Department of Commerce importation data and went to state that: "... this lim ited amount of fibre (crocidolite) was never used for insulation." This latter statement was given further authori ty with a declaration attributed to Hueper [9]. In the paper by Mancuso [8] earlier data was repeated and did not reference nor cite his earlier paper in which analysis of six insulation specimens obtained from locomotives showed that four contained amosite only (analyses by F.D. Pooley, University of Wales). The papers by T.F. Mancuso stood in diametric opposition to advertisements which appeared in trade journals, The Engine, of almost 100 yrs ago (1897) which proclaimed the availability of blue asbestos removable boiler and steam pipe covering, for loco motives. These materials were still advertised 25 yrs later (Asbestos, August, 1921) [10]. Crocidolite importation into the USA The data used to bolster their exposure theory were later challenged [10]. Data for importation of raw crocidolite fibre into the USA, for the years 1916 through 1930, was from the Department of Commerce [1], and those available from the United States Bureau of Mines (as provided in their yearly reports titled "Mineral resources") [10]. These data differ consid erably. Prior to the first import figures shown [10] in the time period 1916-1929, rather than "no data" for both crocidolite and amosite (generally inter preted as "none"), 35,040 metric tonnes of crocido lite found its way to USA asbestos manufacturers. It is important to note that these importation figures are for unprocessed fibre, not for finished products. That 35,040 metric tonnes of fibre were used entire ly for valve packings and woven braids is doubtful. ASBESTOS IN THE LUNGS OF PERSONS EXPOSED IN THE USA The asbestos cement industry was growing, and con sumed much of the fibre. However, crocidolite was used in insulation products. Crocidolite in USA insulation products Importation figures provided by the United States Bureau of Mines showed that crocidolite greatly increased in the USA as the result of lagging required for shipbuilding during World War I, and expe rienced another period of tonnage importation just prior to World War II. It was further concluded that based on marketing data found in the trade journal Asbestos that amosite had replaced crocidolite as a component of high temperature insulation rather than the other way around. The American company Asbestos Limited, which held an association with Cape Asbestos, Ltd. of London, was headquartered in New York City*. Its fibre processing plant was located in Boundbrook, New Jersey. It was here that blue fibre was opened and carded, according to customer specifications. Raw crocidolite was derived from deposits in Griqualand (the operation located in the Asbestos Hills of South Africa, north of Koegas and just south of Kuruman, the locality studied by Wagner et al. [3]). Asbestos Limited manufactured magnesia block insulation, advertised as "Best 85% magnesia is made with blue asbestos" (Asbestos, March, 1921). Its application included the product line New Era Insulation, for moderate- and high-temperature systems (Asbestos, July, 1941). Steam locomotives were particularly emphasized. That thermal insulation products contained asbes tos well past the 1930s was verified in a later study in New York City [12], Of 798 asbestos-containing thermal insulation specimens examined in New York City, 11 (-1.38%) contained crocidolite. The exposures of American insulation workers were not adequately described in previous reports. Crocidolite was available and did find its way into USA insulation products. It is only its market share which is unknown. Crocidolite found its way into USA military ship yards Shipyards in the USA, employed the services of thousands of insulators and pipe coverers. Spray insulation containing crocidolite {via the Limpet pro cess) was used in some nonmilitary shipyards (Asbes tos, September, 1936)+. Naval shipyards during World War II engaged in both construction and repair operations. However, the Navy specified the kind of lagging which was to be used aboard American warships, and such re quirements were codified by the Navy Department. Insulation products allowed on ships were to be com posed of asbestos fibre with a specific chemistry. When considering the bulk chemistry of available commercial fibres it was obvious that only amosite could be used and if specifically calls for the use of amosite for machinery and piping insulation [13], However requirements for ships in the UK dif fered. All three major fibre types were permitted to be used on ships and crocidolite was extensively applied aboard warships [14]. Early mesothelioma studies in the UK focused on work in military ship yards [15]. Some international investigators outside the USA interpreted this to mean that crocidolite was also used aboard American ships, and if mesothe lioma occurred among American insulation workers who worked in military shipyards, this was indirect evidence of crocidolite exposure. However, US Naval specifications rebutted this presumption, and the use argument was no more compelling than the impor tation data referred to earlier. Still other investigators suggested that British ships were re-outfitted in USA ports during the war and they had been the source for crocidolite expo sure to American shipyard workers. This most cer tainly occurred, and citations in the literature support this#. In retrospect, insulation workers, at least those who lived in cities with shipbuilding industries, were probably exposed to at least some crocidolite in this manner. However, those engaged in environments where foreign-ship repairs were undertaken during World War II may have experienced significant expo sures; brief periods of work may have resulted in significant lifetime risks [15, 17, 18]. Appendix references 1. Selikoff IJ, Hammond EC, Churg J. - Mortality expe riences of asbestos insulation workers. 1943-1968. In: Shapiro HA, ed. Pneumoconiosis. Capetown, Oxford Univ. Press, 1970; pp 97-103. 2. Hendry NW. - The geology, occurrences and major uses of asbestos. Ann NY Acad Sci 1965; 132: 12-22. Three further points are noteworthy: the corporate headquarters of J. Manville was at 22 East 40th Street, just across Fifth Avenue from Asbestos Limited. The plant in Boundbrook, New Jersey, was located approximately 3 km from the John-Manville (JM) facility in Manville, New Jersey, and the first reports of mesothelioma in the area, attributed to work at JM only, came from Somerset Hospital in Somerville, NJ, about 4 km from Manville and Boundbrook [11], In retrospect, the mesothelioma experience reported was attributed to exposure at the JM facility, but likely con tained cases exposed at the Asbestos Limited facility as well. The proportion of cases from each facility when contributed to the total experience is unknown. +Crociodolite was sprayed, e.g., in the Sun Shipbuilding and Drydock, Co., in Chester Pennsylvania. Tankers from the Gulf Refining Company (e.g., Gulf Belle, Gulf Dawn) were sprayed under decks and on bulkheads; passenger ferries were sprayed as well, e.g. Princess Anne of the Virginia Ferry Company. Asbestos (1936). #Through President F. Roosevelt's office, and the approval of the Congress, A. Harriman negotiated with and received cooperation from East Coast Shipyards to repair British warships in 1940. As an illustrative example, the battleship HMS Rodney was called into action off Greenland to join in the pursuit of the Bismark [16]. The Rodney was crossing the Atlantic on escort duty after which it was to make for Boston to repair one of its engines which had broken down. It steamed on a single propeller. After the sinking of the Bismark, the Rodney resumed its heading for North America. We assume that British warships carried their crocidolite lagging into USA ports. A.M. LANGER, R.P. NOLAN 3. Wagner JC, Sleggs CA, Marchand P. - Diffuse pleu ral mesothelioma and asbestos exposure in the north western Cape Province. BrJIndMed 1960; 17: 260-271. 4. Wagner JC. - Epidemiology of diffuse mesothelial tumors: evidence of an association from studies in South Africa and the United Kingdom. Ann NY Acad Sci 1965; 132; 575-578. 5. Selikoff IJ. - Statement on the proposed asbestos stan dard. OSHA-DOL. Env Sci Lab Report 1984. 6. McDonald JC. - Dose-response relationships for mesothe lioma. Exposure relationships and malignant mesothe lioma. In: Glenn HW, ed. Session V. Proc, Asbestos Symp Dept Mines, Republic of South Africa, 1977; pp. 64-78. 7. Ohlson CG. - Is chrysotile a significant risk factor for mesothelioma? Letter to the Editor. Am J Ind Med 1989; 15: 351-356. 8. Mancuso TF. - Relative risk of mesothelioma among railroad machinists exposed to chrysotile. Am J Ind Med 1988; 13: 639-657. 9. Hueper WC. - Occupational and non-occupational expo sure to asbestos. Ann NY Acad Sci 1965; 132: 184-195. 10. RossM. - A survey of asbestos-related disease in trades and mining occupations and in factory and mining com munities as a means of predicting health risks of nonoccupational exposure to fibrous minerals. In: Levadie B, ed. Definitions for Asbestos and Other Health-Related Silicates. Amer Soc for Testing Materials, Sp Tech Pub 834, Philadelphia, ASTM Press, 1984; pp. 51-104. 11. Borrow M, Conston A, Livornese L, Schalet N. - Meso thelioma following exposure to asbestos: a review of 72 cases. Chest 1973; 64: 641-643. 12. Langer AM, Nolan RP. - Fiber type and mesothelioma risk. In: Spengler JD, ed. Symposium on Health Aspects of Exposure to Asbestos in Buildings. Harvard Universitv Press, 1989; pp. 91-140. 13. US Navy Department Specification 32P6. - Thermal insulation. In: The Bureau of Ships Technical Manual. 1938; pp. 74. 14. Cross A. - What to do about the asbestos currently in ships and industry? Ann NY Acad Sci 1979; 330: 379-381. 15. Harries PG. - Asbestos hazards in naval dockyards. Ann Occup Hyg 1968; 12: 135-145. 16. Kennedy L. - Pursuit. The Chase and Sinking of the Bismark. New York, Viking Press, 1974. 17. Harries PG. - Asbestos dust concentrations in ship repairing: a practical approach to improving asbestos hygiene in naval dockyards. Ann Occup Hxg 1971; 14: 241-254. ' 18. Robbins HM. - Asbestosis. In: Safety Review. 19: No. 10,10. Washington, DC, US Govt Printing Office, 1962.