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FILE NAME Brakes BRK DATE 1970 DOC BRK031 DOCUMENT DESCRIPTION Published Pneumonoconiosis Conference Presentation - Pulmonary Ferrunginous Bodies Studies of their Origin . 18 No. 6/13/87 6/13/87 ae STUNN PLAINTIFF'S DODO STUNN Date 6/13/876/13/87 by JHL TO * : PNEUMOCONIOSIS Proceedings of the International Conference Johannesburg 1969 EDITED BY H. A. SHAPIRO Ph.D. M.B. Ch.B. F.R.S.S.Af. Visiting Professor of Forensic Medicine tes University of Natal Durban CAPE TOWN OXFORD UNIVERSITY PRESS LONDON NEW YORK TORONTO 1970 PULMONARY FERRUGINOUS BODIES 17081478 STUDIES ON THEIR ORIGIN 1708147 8 PAUL GROSS and ROBERT T. P. DE TREVILLE . Industrial Hygiene Foundation of America Inc. 5231 Centre Avenue Pittsburgh Pa 15232 U.S.A. and MARTIN HALLER Mellon Institute 4400 Fifth Avenue Pittsburgh Pennsylvania 15213 U.S.A. Since the discovery by Thomson et al. of structures indistinguishable from asbestos bodies in lungs of urban dwellers of Cape Town more than 6 years ago his findings have been amply confirmed by investigators in large cities as well as some smaller com- munities in Europe and from North America Although it has long been known that filamentous dust particles of diverse composition when deposited in lungs may cause the formation of bodies similar to asbestos bodies these could generally be differentiated from asbestos bodies by their usually opaque and at times irregular contour of the central core and they were then called asbestos bodies However with the advent of industrial production of transparent thin fibers approximating in size and optical microscopic appearance to some of the respirable asbestos fibers the possibility arose that these made fibers could also cause the production of asbestos bodies when inhaled Recently it was demonstrated that these made fibers when injected intratracheally into hamsters and guinea pigs actually did cause the production of structures indistinguishable from asbestos bodies With proof at hand that these golden to brown elongated clubbed but not necessarily segmented containing structures are not specific indications of the presence of asbestos fibers these structures were given the generic name of ferruginous bodies reserving the term asbestos body for those ferruginous bodies in which the central core is known to be an asbestos fiber As Thomson has pointed out the presence of ferruginous bodies in the lungs of urban dwellers suggest contamination of urban air with a filamentous dust resembling asbestos Whether or not this dust actually is asbestos has not been established Because at one time the pathogenicity of asbestos dust was believed to be linked with 86 the production of innumerable traumatic punctures of tissue by the pointed ends of the dust fibers in the minds of some all fibrous dusts were assumed to be endowed with a similarly high pathogenic potential However more than 10 years ago a dust composed of filamentous ceramic aluminium silicate was shown to belong in that category of dusts designated of as biologically inert This type dust produces a pulmonary response having the following characteristics 1. Collagenization is absent or insignificant 2. The anatomic integrity of the air spaces is preserved 3. The changes are potentially reversible This finding of itself should have laid the mechanical theory of the pathogenesis of asbestos dust to rest just as the biologic inertness of diamond dust laid the mechani- cal theory of the pathogenesis of quartz dust to rest Nonetheless the dust of filamentous glass has become suspected of being fibrogenic apparently on the basis of assumed mechanical trauma Yet glass dust derived from flakes of gossamer glass possessing sharp cutting edges when deposi ted in air spaces has been shown to be biologically inert Rats and hamsters were exposed to 3 kinds of fibrous glass dusts uncoated coated with a formaldehyde type of resin and coated with a starch binder The concentra- tion of the dusts in the inhalation chambers averaged 100 mg./m. About 60 of the dust particles were fibrous and their diameter was I After average ... one year of exposure to this heavy concentration of all 3 types of dust of the pulmonary reaction consisted merely focal accumulations of filled macro- argyrophilc argyrophilic phages localized largely to alveoli in the proximal portion of primary lobules The reactive stroma associated with these cells consisted of a few delicate argyrophilic argyrophilic fibers There was no destruction and no oR e Lea adeheatte 1 Pulmonary Ferruginous Bodies **** **** **** t= . ; imatic of the brous with a vever " ed of was dusts type ponse ant ces is ay vat fiw : . eZ a had & e * a an a ay si4 Sep *. a. : yes get ne a : F. "sg aan 2 d the . is of ologic hani- ; uartz t of d of is of dust glass posibe 1 tinds withwith , andand atra- ibers the the rage sure s of erely The cells ers no _ = Fig 1. The pulmonary response to inhaled fibrous glass dust consists only of macro- phages which are filled with this dust The .Zz macrophages are well preserved and show ; no evidence of degeneration There is no fibrosis and alveolar walls are thin From a , i: rat exposed to fibrous glass dust for twelve months at 100 mg Hematoxylin and $- eosin 110 : Fig 2. Ferruginous body washed from the lungs of a hamster exposed to fibrous glass dust for twelve months at 100 mg concentration The ferruginous material * i appears as though fractured Nevertheless the central glass core appears to be con- tinuous Unstained ^ 960 : : he : ; 5 i H Tagen MLE WE Re aes 2 ERA oh oF 88 P. Gross R. T. P. de Treville and M. Haller ( Mak'i ' collagen formation Fig 1 Abundant ferru- dust was rendered iron by magnetic Mak'i ' ginous bodies were found in the hamster lungs separation Although it contains a few Mak'i ' Fig 2 No differences in the reaction to the scattered transparent fibers 50 to 75 ...long 1 ; 3 different kinds of glass dust could be and about I u in thickness the ray diffrac- detected tion pattern was negative for chrysotile The It has been suggested that one source of dust is essentially fibrous As this was the ferruginous bodies in urban dwellers intended to be a preliminary type study only could very well be the asbestos that is com- a few rats and hamsters were employed 10 minuted by the friction of the asbestos- of each These animals were injected intra- containing brake lining against the steel brake tracheally with acqueous suspensions of the - drum of automobiles.1 This possibility could dust The dosage was 2 ^ 10 mg for rats a? 7 er.us 4 >, os oo 7 gr a ee ee ee , TET mr <a te gh met Nae tee i o 7 1 coat an 2 Nee - ae ee ee a Fig 3. This rat was injected intratracheally with 20 mg of iron brake dust and killed one year later Similar to the reaction to fibrous glass there is no fibrosis and alveolar walls remain normal Air spaces contain collections of macrophages which stain because of the ingested dust Hematoxylin and eosin XI10 XI10 darkly Fig 4. Ferruginous body from the lung of a hamster injected with brake dust and killed 6 months later This ferruginous body is an asbestos body It was found in the sediment from saline injected into the lung Perl's stain ^ 960 a smear of be evaluated by animal experiments and was considered worthy of a pilot study before a proceeding with scale investigation Brake drum dust consists mainly of iron a formaldehyde type resin and for- sterite The latter is a mineral which is formed when chrysotile is heated so that it loses its water of crystallization Brake drum and 3 ^ 3.5 mg for hamsters The animals tolerated the dust well and they were killed one year later The tissue reaction to this dust was very similar to that seen in the animals injected with fibrous glass consisting of collections of filled macrophages situated in alveoli clustered in the proximal portion of primary lobules There was no . Haller agnetic a few ^,, long diffrac e The is was y only ed 10 1 intra- of the or rats 1 and olar rkly and r of animals e killed to this in the insisting ophages ' proximal was no Pulmonary Ferruginous Bodies 89 indication of collagenous fibrosis Fig 3 The hamster lungs contained many ferruginous bodies Fig 4 In order to determine the nature of the dust causing the production of ferruginous bodies in the lungs of urban dwellers it has become necessary to identify the material constituting the central core of the ferruginous bodies isolated from the lungs of these people The method of isolation has been published and involves the digestion of small pieces of lung tissue about 300 gm wet weight with % sodium hypochlorite household bleach for 24 hours removal of the remaining undigested lung tissue and resuspension of the centrifuged sediment in a mixture of 50 alcohol and chloroform Ferruginous bodies because of their high iron content have a high specific gravity and will be found in the sediment at the bottom of the tube Carbonaceous material if not dehydrated by excessive strength of alcohol will be found at the interphase between the chloroform and the aqueous alcohol The sediment containing the ferruginous bodies is washed and resuspended in water Ferru- ginous bodies are transferred to electron microscope means of grids from such suspensions by manipulators It may be of interest to observe that the sediment from the lungs consists mostly of angulated color- less glass particles and often contains many more naked fibers of different sizes than ferruginous bodies Some of these naked fibers are obviously made since the ends show evidence of softening as indicated by the formation of loops shepherd crooks or merely bulbous enlargement Twenty ferruginous bodies from as many lungs of city dwellers from Pittsburgh that had been transferred individually to electron microscope M grids were examined by electron diffraction at the Mellon Institute Carnegie University along with 6 ferruginous bodies similarly isolated from lungs of hamsters injected intratracheally with free brake drum dust and then transferred to M grids Inasmuch as the iron encrustation in the ferruginous body interferes with the production of a satisfactory electron diffraction pattern the central filament had to be scanned from end to end to find a region at least 500 x 500 ^ which was free of iron deposits Such an area was found on each of the ferruginous bodies examined and provi- ded a satisfactory electron diffraction pattern Chrysotile which constitutes about 9095 of all asbestos used in the United States is different from other types of asbestos in that it is composed of tubular crystals which give it a unique electron diffraction pattern The other types of asbestos composed of solid filaments require more exact orientation of the fiber in order to obtain the same electron diffraction pattern as that of a stan- dard sample Not one of the consecutive 28 ferruginous bodies isolated and analyzed yielded an electron diffraction pattern which could be identified as that of chrysotile Fig 5 On the other hand of the 6 ferruginous bodies isolated from hamster lungs injected with brake drum dust all gave an electron diffraction pattern characteristic of chrysotile Figs 6 and 7 this in spite of the relative paucity of fibers in the dust by optical microscopy and the negative ray diffraction pattern of the powder These 6 ferruginous bodies were therefore asbestos bodies Since the ferruginous bodies from the human lungs failed to give the electron diffraction pattern of chrysotile the latter can be excluded as the central fiber in all bodies examined to date However because a diffraction pattern was demonstrated the fibers must necessarily have a crystalline structure This excludes such vitreous materials as glass mineral or rock wool and other ceramic fibers At the same time the diffraction pattern is not sufficiently similar to patterns of known samples of amosite or crocidolite to allow positive identification of either but neither is it possible to exclude these or possibly some of the other forms of asbestotic minerals A recent report of an analysis of ferruginous bodies isolated from the lungs of shipyard shown workers in Flushing Netherlands has that these were indeed asbestos bodies inas- much as the central cores consisted of amphibole asbestos Such findings were to have been expected since shipyard workers are exposed to amosite and crocidolite asbestos It should be noted however that the above results do not necessarily apply to the ferruginous bodies of urban dwellers who are not occupationally exposed to asbestos Since 90-95 of the asbestos used in the United States is chrysotile one would expect chrysotile to constitute the central core of at least some of the ferruginous bodies isolated from the lungs of city dwellers i.e. if these people were actually exposed to asbestos dust ee 2 at Lar nytJON bar a + een eng wert . e be Fig 5. Electron photomicrograph of a portion of a ferruginous body from a human lung The region photographed was selected because it is not covered by ferruginous material It measures about 0.3 ^ 1.6... and is from where the electron diffraction pattern was obtained lower right corner This pattern is unlike that obtained with chrysotile compared with Fig 6 Fig 6. Electron photomicrograph to show the central cavity of a tubular crystal of chrysotile The electron diffraction of chrysotile is shown in lower pattern right corner The characteristic and unique feature of this electron diffraction pattern is the exclama- o mnathre k layeorr ld iner s o arproswhape of the pips Fig seen lung dust The 7. Portion of a ferruginous body as under an electron microscope from the of a hamster injected with brake intratracheally and killed one year later naked portion of the central core measures about diffraction 0.06 ^ 0.3... The electron pattern from this region of the core lower right corner resembles that of chrysotile compared with Fig 6 This ferrbuodyginous body is therefore an asbestos vay ! aller Pulmonary Ferruginous Bodies 91 It is of course possible that in continuing 6. Ghezzi I. Molteni G. and Puccett U 656-657 this investigation and isolating ferruginous bodies from the lungs of many more people and examining more than one body per lung asbestos fibers may be identified in their cores Asbestos Bodies in the Lungs of Inhabitants of Milan Med Lavoro 223-227 1967 7. Cooke W. .: Anthracosis Presenting Curious Bodies Similar to Those in Asbestosis Brit Med J. 1932 Nevertheless the failure to find a chrysotile 8. Gough .: Differential Diagnosis in the . core in any of the 28 consecutive ferruginous Pathology of Asbestosis Ann New York Acad bodies examined is considered significant Sci 132 368 3712965 9. Gross P. de Treville R. T. P. Cralley L. J. REFERENCES _ and Davis J. M. G Pulmonary Ferruginous Bodies Development in Response to Fila- 1. Thomson J. G. Kaschula R. O. C. and MacDonald R. R Asbestos as a Modern Urban Hazard S. Afr Med J. 77-81 1963 2. Thomson J. G. and Graves W. M Asbestos as an Urban Air Contaminant Arch Path 81 458-464 1966 3. Cauna D. Totten R. S. and Gross .: Asbestos Bodies in Human Lungs at Autopsy JAMA 192 371-373 1965 4. Anjilvel L. and Thurlbeck W. M The Incidence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal Canad Med Assoc J. 1179-1182 1966 5. Meurman .: Asbestos Bodies and Pleural Plaques in a Finnish Series of Autopsy Cases Acta Path Microbiol Scand supp 181 1966 mentous Dusts and a Method of Isolation and Concentration Arch Path 58 : 539-546 1968 10. Gross P. Westrick M. L. Schrenk H. H. and McNerney J. M The Effects of a Synthetic Ceramic Fibre Dust upon the Lungs of Rats AMA Arch Indust Hlth 161166 1956 II Gross P. Westrick M. L. and McNerney J. M Glass Dust A Study of its Biological 10-23 Effects AMA Arch Indust Hith 21 1960 1960 12. Gross P. de Treville R. T. P. and Haller M Pulmonary Ferruginous Bodies of City Dwellers A Study of Their Central Fiber to be published in Arch Environ Hlth 13. Stumphius J. and Mayer P. .: Asbestos Bodies and Mesothelioma Ann Occup Hyg 11 283-293 1968