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PLAINTIFF'S EXHIBIT INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, Inc. Medical Series, Bulletin No. 12 THE PNEUMOCONIOSES 4400 Fifth Avenue Pittsburgh Pennsylvania 15213 1967 i 5 -/ ASARCO ELP 0005123 THE PNEUMOCONIOSES 4400 Fifth Avenue Pittsburgh. Pennsylvania 15213 1967 ASARCO ELP 0005124 FOREWORD The Foundation's first medical series bulletin entitled, "Silicosis and Allied Disorders" was prepared under the supervision of Dr. A. J. Lanza, Long out of print, this publication was considered by many to be the best avail able and most useful statement of what was known and not known about silicosis in 1936. Much of its contents are still valid and occasional requests for it are still received. Dr. Paul Gross, Director of IHF Research Laboratory, and I were recently asked to assist the American College of Chest Physicians by preparing a section on The Pneumoconioses for consideration for possible use in a reference text, "Cardiac and Pulmonary Physiology, " sponsored by the College. We have elected to prepare this bulletin as a first step towards such a section, feeLing that critical review of this material in its present form will be received from within and without the Foundation's membership and that mean while, its contents may provide useful guidance to physicians responsible for evaluating, controlling and preventing chronic lung disease in employed popula tions exposed to dusty environments. We recognize that there is need for much more (and more precise) knowledge of the manner in which human lungs respond to injury. The Founda tion's Laboratory will continue its efforts to explicate the pathogenesis of the pneumoconioses. of emphysema and of lung cancer caused by environmental factors. Meanwhile, we will appreciate receiving data on which to base cor rections and other improvements of this text prior to submitting it for publica tion in the open literature. Robert T. P. deTreville, M.D. Managing Director, IHF i s ASARCO ELP 0005125 I. Purpose? INTRODUCTION The purpose of this communication is to provide systematized factual information on the pneumoconioses not readily available elsewhere. What the pneumoconioses are, how they differ from other diseases, their diagnosis, prognostication, and preventive medical practices are expected to involve all medical practitioners to an increasing degree as a result of increasing public awareness of and interest in control of the environment. It would, of course, be impossible to include here comprehensive coverage of all of these areas of importance; however, carefully selected references are cited by means of which the interested reader may further develop proper orientation and famil iarity in any of the areas discussed, such as methods and interpretations of pulmonary function testing, or techniques of environmental survey and analysis, for example. Chief attention is directed to anatomical and pathological con siderations, as these, rather than the clinical and physiological aspects of the pneumoconioses have been most important diagnostically and from a forensic standpoint. Chronic obstructive bronchopulmonary disease, a symptomatic condi tion commonly found in the general population, often occurs in coal miners and in other workers; it may thus "complicate11 a simple or complex dust reac tion. This association should by no means be interpreted to mean that chronic bronchitis or symptomatic emphysema (or both) are a result of the pneumoco- niotic process. Such data as exist and are presented here suggest that such a relationship has not been established, although further data are needed to further document this position and these are being gathered. ASARCO ELP 0005126 z. Definition: It is An understatement to say that there is no unanimity as to what constitutes pneumoconiosis. At an international conference2 of experts in 1950, pneumoconiosis was defined as . . a diagnosable disease of the lungs produced by the inhalation of dust. ..." As a result of the acceptance of this definition. It could happen that a coal miner may be demonstrated to possess black lungs at autopsy, whereas he was not considered to have had pneumoco niosis (even in retrospect) a few hours previously during life---because it was not diagnosable.* As described later under Coal Workers Pneumoconiosis, a few years after the above definition of pneumoconiosis was adopted, an attempt was made to broaden the term pneumoconiosis to include symptomatic emphysema of the coal workers, and this concept has recently been introduced into law in the State of Pennsylvania. There are no good data to substantiate such an etiologic association, and in our opinion, socio-economic rather than scientific consid eration appears to have been foremost in this legislation. General Considerations: Environmental--As described in detail elsewhere, ^ only a fraction of the dust suspended in air is respirable. Generally, particles larger than lOp. in diam eter are filtered out by the nasal passages. Particles down to 3p in diameter are largely trapped on the tracheo-bronchial mucosa by their momentum, as a result of abrupt changes in direction of the dividing tubul-es of the bronchial * As used in this Bulletin, unless otherwise stated, the term "pneumoconiosis'' refers to the deposition of dust in the lungs and the pulmonary reaction to its presence. ** 77 Purdon's Statutes Section 1208 (K). (An Amendment to Section 108 (KJ to the Pennsylvania Occupational Disease Act, dated Nov, 10, 1965, effective Dec. 1, 19b5.) \ t l ASARCO ELP 0005127 3. air-conducting system and by gravity as well. Also, as the tubular airways subdivide, there is a progressive decrease in the airflow rate until, in the alveoli, it approaches zero. Larger and heavier particles thus settle out before reaching the alveoli. Particles visible with the optical microscope and less than in diameter reach and may be deposited upon the alveolar i 1 surfaces; however, they do not necessarily remain in the lung. Alveolar Clearance--The lung possesses a very efficient self-cleaning mechanism which is estimated to be 98 to 99 per cent efficient---even when some what overtaxed. Dust that becomes stored in the lung is, accordingly, the result of the one to two per cent inefficiency. From the point of view of prevention, increased attention should, therefore, be directed to the effectiveness of the a individual worker's clearance mechanism inasmuch as a reduction in the efficiency of dust clearance of only one per cent from 99 to 98 per cent may thereby double the amount of dust stored in the lung! It is generally stated that if 100 men are l exposed to an atmosphere with known serious silica hazard for the same length i of time, only 25 will develop pneumoconiosis (see page 20). What is responsible for the greater susceptibility in the 25 per cent affected is not laiown, but reduced effectiveness of the pulmonary clearance mechanism is undoubtedly an important \ factor. There are two theories concerning the mechanism of alveolar clear ance: one that has been taught for about a century is based on the vitalistic concept that dust-filled alveolar macrophages migrate by directed ameboid motion (tropism responsible for the direction is unknown!) to the terminal bronchiole there to join the proximally moving mucous blanket. The other fc- i X r % * i* ASARCO ELP 0005128 4. hypothesis is only L5 years old. According to the latter, a film of fluid (described by the Canadian anatomist, Macklin, to be about 0. 2p. thick) covers the alveolar surface and moves from the periphery to the terminal bronchiole. Inhaled dust particles, coming to rest upon the alveolar surface either as naked particles or within macrophages, are transported to the muco-ciliary escalator passively by the moving film. The area drained by the surface film is estimated to be 500 times greater than that of the respiratory bron chiole, which may be graphically represented as the narrow end of a large funnel. In our opinion, this concept best explains the observed tendency for particulates (which are cleared rapidly from alveoli within a few days after experimental dust exposure) to accumulate and stagnate in the respiratory bron chiole itself, and, more especially, in its alveoli. Delicate tissues in this loca tion may thus be exposed to relatively higher concentrations of noxious materials for much longer periods of time than elsewhere in the lung. Consequently, tissue reactions to inhaled noxious materials would localize in the region of the respir atory bronchiole. The fact that such localization is easily demonstrated experi mentally would appear to validate such a hypothesis, at least in the several animal species which have been used. Pathological Classification of Dusts - Fibrogenic versus Inert--The alveolar friembrane's response to the presence of inhaled insoluble particles is a demonstrable proliferation of cohesive cells upon'the alveolar surface. Simultaneously, an elaboration of argyrophilic fibers may be seen; first manifested by increased arborescence of immature (argyrophilic) fibers and subsequently, by a netwo^'- -x*r*^h elaborated fibers that support the pro- v. mmm ASARCO ELP 0005129 5. liferated cells. Where exposure is to dust alone, the subjacent capillar/ does not participate in the reaction. The proliferated tissue therefore is, and remains, avascular. This alveolar membrane reaction effectively sequesters inhaled particles within the proliferated cell mass. The sequestration of inhaled dust is not necessarily permanent. As long as the inflammatory stroma remains argyrophilic and does not convert to collagen, it may resolve and dis appear and thereby release the imprisoned cells and dust. This undoubtedly explains the continued expectoration of black sputum by coal miners many years after leaving the dusty environment. The avascular reactive argyrophilic stroma of the alveolar membrane is of entodermai. rather than mesodermal origin. Characteristically, it tends to mature into adult collagen either late or. often, not at all during the life time of the individual. Some dusts, notably quart2, evoke an alveolar mem brane reaction with abundant argyrophilic stroma that matures after a short interval of weeks to months into adult collagen. In contrast, the reactive tissue produced in the lung by coal dust or kaolin is characterized by relatively scanty, argyrophilic stroma that matures very little or not at all. It is on this basis that dusts have been classified as either fibrogenic or nonfibrogenic. The latter term is also called benign or "biologically inert, " "inert" here being used in a relative sense. It is important to note that not all dusts can be class i1 ified as being "fibrogenic" or "inert. " Many of the "in between" dusts are silicates, feldspar being a good example; and such dusts produce more abun dant argyrophilic fiber formation, with limited conversion of the fibers to collagen. ASARCO ELP 0005130 6. Mixtures of Dusts -- Practically speaking, human exposures differ from those in the experimental laboratory in an important respect: in most dusty jobs, a worker is exposed not to one dust, but to mixtures of dusts, the fibro. genic potential of which vary from low to high. Thus, in industry it is common to find workers who have been exposed to mixtures of coal and quartz dusts, the former possessing low fibrogenic potential. Among other dust mixtures to which workers may be exposed are: iron oxide plus quartz, asbestos plus cement, kaolin plus quartz, asbestos plus quartz, and limestone plus quartz, to mention only a few of the more common mixtures which have been prevalent in the past. While dust control measures have greatly reduced levels of dusti ness to which workers were exposed in many industries prior to 1940, a number of potentially hazardous conditions still exist in some operations where such controls have not been maintained or, in some cases, have never been installed. Clinical--As indicated in ''Definitions, " ultimately, presence or absence of pneumoconiosis is based on anatomic or pathologic grounds and, therefore, during life it may be impossible to make an accurate diagnosis. His tory of prolonged exposure to dusts capable of causing pneumoconiosis is often not accompanied by any evidence of disease by physical examination, and such changes as are present in radiological or physiological findings may not be paeumocoaiotic in origin (see page 8). The outstanding exception consists of an important disease complication--progressive massive fibrosis (PMF) (see pages 9 and 23). The chief value to be derived from quantitation of measurable defects by pulmonary function tests and X-rays may be in locating individuals with the highest risk of developing PMF. We need to learn more of the natural history of these individuals in the absence of exposure to dust and also to avoid ASARCO ELP 0005131 7. any possible acceleration .of their further deterioration which might result from exposure to dusty environments. Regarding job placement, the late Dr. A. J. Lanza had said in 1937 that an individual with known tuberculosis should not be exposed to an environment suspected to have an associated silicosis hazard.^ This admonition holds today, but we now suspect that the tubercle bacillus is only one of a number of organisms capable of producing PMF in coal miners.^ In addition to massive respiratory exposure to coal dust, some infectious process or other appears to be essential to the production of PMF. and genetotrophic and sociological factors are also undoubtedly contributory. Regarding the question of destructive lung disease (symptomatic emphysema) and dust exposure, the chief goals of retrospective and prospective environmental health research studies are: (1) to identify among apparently healthy individuals those with high risk of developing pulmonary emphysema, (2) to provide them sheltered work situations, applying prac tical health conservation procedures, and (3) to measure the effectiveness of such preventive measures to the best possible degree. In contrast to acute bronchopulmonary conditions which may signal their presence clinically with alarming accompanying signs and symptoms, chronic bronchopulmonary disease is usually not diagnosable until extensive because of an effective physiological j "safety factor, " the reserve capacity of the lungs. Fifty per cent or more of the lung's normal function may be lost without subjective recpgnition of malfunction in persons performing the usual work required by modern living; a similar degree of loss may be necessary before unquivocal evidence of emphysema may be detected by clinical examination, in the absence of measure- $* t. V ^ C * ASARCO ELP 0005132 J 8. ment of gaseous diffusion across the alveolar membrane. Even where evaluation of lung function in a well-equipped pulmonary physiology laboratory is performed interpretation of results (concerning functional loss and prognosis) is made dif, ficuit when there are no baseline measurements on the individual being studied.7 Lung function tests are not specific in regard to etiology, in general, and 6 this appears especially true in the pneumoconioses. The ranges of normal var- iation in pulmonary functions are great, and unless there are existing values against which to compare findings in individuals, there is no way of being sure that conclusions concerning functional loss at the time of testing are actually valid. The decrement produced by age must be considered in such an evaluation, as it may be very significant. Other factors to be evaluated are cigarette smok ing and recurrent acute pulmonary infections, both of which are common findings ; in histories obtained from individuals with chronic obstructive bronchopulmon- f ary disease. Of a number of excellent references on pulmonary function evaluation, David V. Bates and Ronald V. Christie's 8 Respiratory Function in Disease. o and E. A. Gaenslet and C. W. Wright's "Evaluation of Respiratory Impair ment, " which review the various means of evaluating respiratory impairment f are highly recommended. Both give examples of proper use and interpretation of pulmonary function tests. Techniques and laboratory equipment differ widely, but there is general agreement concerning the ability to compare data derived from different techniques, provided that individuals'performing the tests had developed their own laboratory controls and were sufficiently experienced. "Pulmonary function studies on an individual at one point in time are useful, but even more important are repeated studies in which individuals serve as their V H, ASARCO ELP 0005133 m 9. own controls. In epidemiological studies performed in different industrial en vironments for research purposes, it is most important to follow cohorts, including those who leave the industry, perhaps because of some specific health problem of importance, as well as those who remain, representing those less susceptible to harm for one or another reason."^ Radiological--Because of the importance of the chest film to the detec tion of pneumoconioses, great care has gone into the preparation of an "inter national classification of persistent opacities in the lung fields provoked by the inhalation of mineral dusts''*^ ** shown in Table 1.* 11-12 More recently, however, the U. S. Public Health Service has modi fied this classification along lines shown in Table 2. In addition, a classifi cation to aid interpretation of X-ray films in individuals suspected cf having 12 asbestosis is being prepared in support of U S. Public Health Service as bestos chest studies currently in progress. Although not yet published, ten tative guidelines dated October 1, 1966 have been circulated for comment and may be available upon request to qualified research personnel through the Department of Health, Education and Welfare, Bureau of Disease Pre vention and Environmental Control, National Center for Urban and Industrial Health, Occupational Health Program, Cincinnati, Ohio 45202. * In agreeing to the reproduction of this Table here, Dr. Luigi Farmeggiani (Chief, Occupational Safety and Health Branch, Conditions of Work and Life Department of the International Labour Office) also offered the Foundation permission to publish illustrations based on the set of standard X-ray films which illustrate the International Classification. It would be difficult to at tempt to compare X-ray films to such printed illustration, however; those wishing to obtain sets of standards should order them directly from Dr. Parmeggiani. Cost of the set of 14 standardl4" x 17" films is $25.00. : J! / r 1111 / r ASARCO ELP 0005134 10. Table l INTERNATIONAL CLASSIFICATION OF PERSISTENT RADIOLOGICAL OPACITIES IN*Tw LUNG FIELDS PROVOKED BY THE INHALATION OF MINERAL DUSTS* ^ (Geneva, 1928) Tjpc of opacuy QujUuuvc fca.u res Quantitative fcaiLTd Additional symbols No pMumo* SUSPECT COIUOSU Linear opacities PNEUMOCONIOSIS Small opacities Ufee opaoix4 oZ "% 1 <"> t9 m A A \ X J 1 ji3 I 2 J 1 <di> J(cm) (h > ( P<) 0 <P*) c (lb) * IlKIwtflAf (014 **J CUtOA SutU. DEFINITIONS AND COMMENTS The sbied oftht ttestification it to codify ike radiological appearances of ike pneumoconioses in a simple, to.til/ doable wu . It it intended to describe the radiographic appearances of the persistent opacities associated with pntu^ Content. <* to depot pathological entities. nor to take into account the question of working capacity, r, here tiure is an appreciable difference in the appearance of the two lungs, the two appearances may be dtscnbg separately, beginning with the right lung. J mocoruori* No radiographic evidence of pneumoconiosis. Suspect opacities Z Increased lung markings. Linear opacities Pneumoconiosis L Numerous linear or reticular opacities, the lung pattern being normal, accentuated or obscured, j Small opac.ua 1 ii Large opacitia* The following types are defined according to tht greatest diameter of ike predominant opacities. p Punctiform opacities. Size up to 1J mm* m Micro-nodularormiJury opacities. Greatest diameter between 14 and 3 mm. n Nodular opacities. Size between 3 and .. 10 mm. The categorisation depends on the extent and the profusion ofthe opacities. Category 1: A small mimber of opacities in an area equivalent to at least two anterior rib spaces and at the most not greater thaa one-third of the two lung fields. Category 2: Opacities more numerous aod diffuse thaa in category 1 aod distributed over most of the lung fields. Category J: Very numerous profuse opacities covering the whole or nearly the whole of the lung fields. A An opacity having a longest diameter of between 1 and 5 cm, or several opacities each greater thaa ] cm. the sum of whose longest diameters does not exceed 3 cm. B One or more opacities, larger or more numerous than thou in category A, whose combined area doc not exceed one-thtrd of one lung field. C One or more large opaques, whose combined area' exceeds ose-third of one Jung Held* Additional symbob co) abnormalities of the cardiac outline. To be replaced by (cp): cor pulmonale, if this condition is strongly suspected, Recommen ded addi tional symbol* * cv) di) cm) hi) pi) canty. significant distortion of the intra-thoracie organs. marked emphysema. marked abnormalities of the hilar shadows. significant pleural abnormalities. px) pneumothorax. tb) opacities suggestive of active tuberculosis. TH Ow4 f'ha UNiUk 1 ni m tl Un "* * m (!.mM R* Kno--. T)w toe***** * M*U **** *** * P*OM f o'*u*iuL t: f ASARCO ELP 0005135 Table l INTERNATIONAL RADIOLOGICAL CLASSIFICATION OF CHEST FILMS MODIFIED FOR U.S.P.H.S. CHEST STUDIES TYPE OF OPACITY FILM QUALITY NO PNEUMO CONIOSIS SUSPECT PNEUMOCONIOSIS SMALL OPACITIES |LARGE OPACITIES* UNSAT. FILM POOR FILM quantitative features qualitative features additional SYMBOLS riLM QUALITY NO PNEUMO CONIOSIS SUSPECT OPACITIES SMALL OPACITIES 1 2 3, | 0 z 1J ;i 1 Pjqjr P i q [ r p!q;r is ox ca cn co cv di em $ 1 hi pi | px rl __ I_____ UNSATISFACTORY FILM - IMPOSSIBLE TO READ POOR FILM* DETAILED CLASSIFICATION DIFFICULT A A fb B tba nf C np O-NO RADIOGRAPHIC EVIDENCE OF PNEUMOCONIOSIS IN LUNG FIELDS. 7. SHADOWS WHICH MAY BE PNEUMOCONIOTIC BUT WHICH ARE INSUFFICIENT FOR THE c film to be placed in one of the categories classifying the small opacities. PNEUMOCONIOSIS SPACES or CITHER JlOC.AKO AT THE MOST.MOT GftCATCft THAN OHC THIRD 0F THE TWO LUNQ riCLOS eousiNCO. 7 opacities woke otrruu than im category t ^-WNICH MAT ( OlSTftliUTEO OVER THE WHOLE Oft NEARLY THE WHOLE Of THE LUNG flCLDS. O VERT NUMEROUS OPACITIES OlSTRUUTCO OVER THE WHOLE.Oft NEARLY THE WHOLE Of THC LUNQ YIELDS. ThCSC arc CLASSIPiCO ACCOROIHC to THE GREATEST OIAMCTCR Of THC PRCOOMHAMT OPACITIES ANO OCNOTEO IT THE FOLLOWING STHROLS : p>GREATEST OIAMCTCR UP TO AHOINCLUOING LSaa. -GREATEST OIAMCTCR PROM U INCLUOlHO la. ^ ft. LARGE OPACITIES EGGSHELL CALCIFICATIONS (ES) A* AN OPACITY HAVING A GREATEST DIAMETER EXCEEDING 1 a ANO UP TO AHO INCLUOlHO S is. OR SEVERAL OPACITIES EACH GREATER THAN t-..THC SUM Of WHOSC GREATEST OlAwCTCRS OOES NOT EXCEED S is -0*C OR MORE OPACITIES LARGER OR MORE NUMEROUS THAN THOSE IN CATEGORY A WHOSC COMIINCO *ft|A DOES NOT CXCECO ONE THIRO Of THE VISIBLE RIGHT IUMO. C-OHC OR MORE OPACITIES WHOSE COMSINCD AREA CXCCCOS OHC THIRO Of THC VI3ISLC RIGHT LUNG fltLO. Specific CRITERIA FOR IDENTIFYING EGGSHELL CALCIFICATIONS AS EVIDENCE OF SILICOSIS: (I) THE PRESENCE OF SMCLL*LIKC CALCIFICATIONS MEASURING UP TO 2 as. IN THICKNESS IN THCPCRIPhERAL ZONE OF AT LEAST TWO LYMPH NOOCA. tt) THESE CALCIFICATIONS MAY SC SOUO OR IftOKCN. (SIM AT LEAST ONE OF THE LYMPH MOOCS THC RIMG'LIKC SHAOOW MUST SC COMPLETE. (AITHC CENTRAL PORTION OF THC LYMPH MODE MAT SHOW.IN AOOITIOM. SPECRLEO CALCIFICATION. (SITNC AFFECTED LYMPH NOOC MUST SC AT LEAST Us. IN ITS 0RCATCST OIAMCTCR. CODE FOR ADDITIONAL 5YM80LS > - SUSPECT COALESCENCE OF SMALL PNEUMOCONIOTIC OPACITIES < SUSPECT CANCER Of THE LUNQ c* CALCIFICATION IN SMALL OPACITIES a-EGGSHELL CALCIFICATION Of LYMPH NOOCS lil -APPRECIABLE ENLARGEMENT OF THE HILAR SHADOWS pi - ABNORMALITY OF THE PLEURA pa -PNEUMOTHORAX - ABNORMALITIES Of THE CARDIAC OUTLINE. TO 1C RE PLACED rhI*mM# IF THIS CONDITION IS STRONGLY SUSPECTED - CAVITY SI -SIGNIFICANT DISPLACEMENT OR DISTORTION Of THE INTRA-THORACIG ORGANS -EMPHYSEMA rI -PNEUMOCONIOSIS MODIFIED BY THE RHEUMATOID PROCESS lb-OPACITIES SUGGESTIVE OF INACTIVE TUBERCULOSIS. EXCLUDING THE CALCIFIED PRIMARY COMPLEX lba*OPACITICS SUGGESTIVE OF ACTIVE TUBERCULOSIS t -NON-TUIERCULOUS INFECTION p-PROBABLY NOT PNEUMOCONIOSIS * THC BACKGROUND OF SMALL OPACITIES SHOULD BE SPECIFIED AS FAR AS POSSIBLE. CATEGORY 1 CATEGORY B CATEGORY C RADIOLOGICAL VISUALIZED 1 RADIOLOGICAL APPEARANCE APPEARANCE j APPEARANCE VISUALIZED APPEARANCE SJ RADIOLOGICAL APPEARANCE I VISUALIZED APPEARANCE m ! ; Li ASARCO ELP 0005136 Typea of Pneumoconiosis l Nonfibrogenic (also called ''benign1*) Pneumoconioses or "Dirty Lungs"? ``Dirty lungs" ar caused by nonfibrogenic or "inert" dusts. This condition is not associated clinically with either symptoms or impairment of lung function. Dusts capable of producing such asymptomatic changes include coal, carbon, kaolin, cement, iron oxide, tin oxide, barium sulphate, natural (uncalcined) diatomaceous earth, and others. 'Although evidence is lacking, it is repeatedly stated that massive amounts of such "inert" dusts in the lungs may damage enough alveolar tissue to produce symp toms. Whether or not this is true, it has been demonstrated clinically as well as experimentally that when the amount of "inert" dust in the lung is truly massive, an infection even though of low virulence, may result in widespread, progressive and fatal pulmonary fibrosis. Examples of such disease have been seen in coal workers (see PMF, page 21), and in workers exposed to kaolin dust, as well. Some nonfibrogenic pneumoconioses are of considerable practical im portance because chest radiographs in such cases always present an interesting diagnostic challenge. These may easily be misinterpreted by physicians un familiar with their appearance. The result is usually needless alarm of the patient and, at times, iatrogenic neurosis. This has occurred in cases of siderosis in which there are sharply defined miliary shadows in the chest radiograph. Differential diagnosis of "benign" pneumoconioses Is discussed by Johnstone and Miller^ who describe the necessary steps in the diagnosis of an occupational disease. ASARCO Et-P I t i 13. SILICOSIS Uncomplicated (non-infectious) silicosis is an occupational disease which has no pathognomic signs and symptoms. The diagnosis is made on the basis of the occupational history (including the number of years expo sure to adequate concentrations of dust of a respirable size containing signifi cant amounts of free quartz, i. e., levels of exposure in excess of Threshold Limits*^) and findings on chest X-ray examination. In addition, other aspects of the clinical investigation are essential to distinguish between findings re lated to dust exposure and those which may be irrelevant. Skillful clinical appraisal is essential in differential diagnosis and prognostication, as many chronic diseases (e.g. , miliary tuberculosis or widely disseminated metastatic carcinoma of the lung9) may on a single occasion provide X-ray densities sug gestive of silicotic fibrosis. A diagnosis of silicosis usually does not mean impairment, and ability to work (or decreased work capacity must therefore be stated. Evaluating pulmonary impairment in the presence of chronic bronchopulmonary disease may be a difficult matter. (See General Considerations.) 9 Drs. Gaensler and Wright indicate that respiratory impairment may be cate gorized best in terms of a few relatively broad classes; Class O has no measur able impairment (0-10%), while Class 4, at the other extreme, includes those with obviously severe impairment who have difficulty caring for themselves and might be classified as 90-95% impaired on simple clinical observation. Between these extremes, three other groups are recognized: Class 1 with ASARCO ELP 0005138 r V4 14. minimal impairment from all causes in whom respirator/ impairment could not be construed to contribute significantly to disability; Class 2 which has moderate impairment for heavy labor or strenuous recreational activities but which is usually significant only when accompanied by impairment of other organs; finally, Class 3 which includes severely impaired patients who manage ?; to be gainfully employed only under special circumstances and in whom respir atory insufficiency may well be the sole reason for total disability. In addition, a suffix MX" may be added to the above classes to indicate variable impairment due to factors other than measurable physiologic disturbances (e.g., a persis tent tuberculous cavity with a positive sputum). These classes were reportedly developed at the request of the Committee on Rating of Mental and Physical Impairment of the American Medical Associa tion, which has modified them as follows:^ Class 1 Class 2 Class 3 Class 4 (0% by definition if under 20%) (20-30% impairment of the "whole man11) (40-50% impairment of the "whole man") (60-90% impairment of the "whole man") The AMA guide urges that the one final impairment value in an individual be j* expressed to the nearest 5%; however, Drs, Gaensler and Wright recommended r against such close calculations that "imply a precision of measurement which, in fact, does not exist;" further, they indicate that the pulmonary reserve is so great that small degrees of impairment could not possibly refledt in terms of disability. Finally, they express doubt that the mathematical addition or t Ntrt- ASARCO ELP 0005139 r 4 J: ; rj t\ `! 15. combination of multiple systems impairments by preconceived formulae is an appropriate way to express the total medical effect upon the whole man. It is important that the physician attempting to use the AMA guide recognize such shortcomings in the rating system and use his best clinical judgment, supported by appropriate pulmonary function laboratory findings. Physical Examination---Except in the late stages of silicosis, compli cated by infection as described below, little'is revealed by clinical examination of the chest. As stated above, recognition of silicosis in the individual by means of physical examination alone is very often impossible. A clear history of re peated or long-term exposure to free crystalline siLica of respirable size should be sought and the chest X-ray is indispensable in arriving at a positive diagnosis in silicosis. (X-ray interpretation and classification are discussed on pages 9 and 23}. Pathological Diagnosis: Silicosis is a fibrous, nodular disease of the lungs, caused by the pres ence upon the alveolar surface of crystalline silica (most often quartz). As a matter of practical experience, it is rare and becoming more so that a worker is exposed to only one dust during his lifetime. If other inhaled dusts (such as asbestos, cristobalite, or tridymite) are also fibrogenic, the net effect is summative. Otherwise, the superadded inhaled dusts probably do not contribute significantly to the uncomplicated clinical silicotic disease. , In uncomplicated silicosis the lung contains widely distributed sharply defined hard nodules 2 to 4 mm in diameter, the number and size depending upon the severity and duration of the dust exposure. These nodules may be more numerous in the upper, than in the lower lobes. Upon gross examina- ASARCO ELP 0005140 16. tion of the cut surface of the lung* the color of the nodules may vary from gray to black, depending upon the admixture of other dusts, particularly the carbonaceous ones. These nodules are the repository of the residual inhaled silica, sequestered within concentrically arranged dense collagenous tissue. The nodules tend to increase in size with continued exposure, the growth occurring in the so-called peripheral reactive zone in which the newly deposited silica is abun dantly present. With the cessation of exposure, the peripheral reactive 2one tends to become progressively more narrow and finally to disappear. The nodules are then largely acellular and the disease is in an inactive, nonpro gressive state. It is important to appreciate that in uncomplicated silicosis, the lung tissue between the nodules is anatomically and functionally normal.* Silica is readily transported from the lung tissue to lymph nodes of the hilar and paratracheal regions as well as beyond these areas. As a result, nodes so involved tend to become enlarged and stony hard, their color depend ing upon the presence of other dusts. The mechanism by which the crystalline silica produces its pathologic effect is not known. Of the numerous theories which have been proposed, the one now being given most serious consideration involves surface action and immuno- ,logi.c mec.han.isms. 6 " ' i i r * Mention should be made here of so-called "acute silicosis, " a rare, diffuse, inflammatory lesion of the lungs which has occurred sporadically, often in epidemics (e.g. , Gaulley Bridge), where workers have been overwhelmingly exposed to crystalline silica dust having a large component under lp in dia meter. The lungs initially respond to such exposure by acute inflammatory changes, followed by a diffuse type of fibrosis not characterized by typical nodules but by confluence of micronodulea, and in some cases, dense fibrosis m the upper lobes. Evidence of complicating infection may be present. An other diffuse, non-nodular form of silicosis is "Diatomite Pneumoconiosis" i caused by cristobalite, tr*"4-'--'** and quartz which are produced by calcination of amorphous diatomaceous earth. ^ < \ ASARCO ELP 0005141 ' 17. Chronic Obstructive Bronchopulmonary Disease (Including Symptomatic Emphy sema and Chronic Bronchitis): In discussing the symptomatic emphysema and chronic bronchitis encoun tered in silicotic subjects, it should be stressed at the outset that we do not intend to imply either an etiologic or an aggravating relationship between the existing silicosis and these complications. There exists today in a large seg ment of the adult population and in housewives as well as workers in industry trades, recognizable chronic obstructive bronchopulmonary disease; and the fact that this condition is observed not infrequently in silicotics should not be surprising. Tuberculosis, which is much less prevalent in the general popula tion than emphysema and chronic bronchitis, remains the most dreaded com plication of silicosis. (It accounted for roughly 75% of the deaths of silicotics a generation ago. ) The important difference in the relationship of these two diseases to silicosis is essentially this: whereas tuberculosis, in combination with silicosis is synergistic (resulting in a new and therapeutically-resistant entity, silicotubereulosis), the chronic obstructive bronchopulmonary disease encountered in silicotics is no different clinically or pathologically than that found in the general population. Although it is true that the air spaces adjoin ing silicotic nodules, similar to those adjacent to other types of scars, may exhibit so-called "traction," or paracicatricial emphysema, this usually has no clinical significance. There is no relationship between such anatomic find ings and symptomatic disease associated with the panlobul&r and centrilobular forms of emphysema.*^ Depending upon the severity of the chronic obstructive bronchopulmonary disease, there is usually an associated reduction in the total vascular bed of the lungs, resulting in cor pulmonale. This may lead to cardiac failure ASARCO ELP 0005142 r is. and death. Although vascular sclerosis has been described in silicotic lungs, it is doubtful that silicosis without a coexisting panlobular emphysema or chronic bronchitis could give rise to pulmonary hypertension. Nevertheless, at a re16 cent Symposium on Coalworkers* Pneumoconiosis held in Morgantown, West Virginia, May 18-20, 196?, mention was made of clinical research in this area using cardiac catheterization as a means of detecting increased right heart pressure. Tuberculosilicosis (or Silicotuberculosjs): The combination of silicosis with tuberculosis tends to produce extensive fibrous solidification of the lungs. Cavitation is. of course, also common. The recognized tendency for a superimposed tuberculous infection to cause enlargement of the shadows of the individual silicotic lesions on the chest radiograph has led experts to believe that most, if not all, confluent silicotic lesions are caused by superadded tuberculous infection. Likewise, the ap parent progressiveness of some silicotic lesions after removal of the worker from further exposure to silica dust has also been attributed to a superimposed tuberculous infection. Fibrous pleuritis, a not uncommon finding in silicotics, is caused by intercurrent infection, unrelated to the presence of silicotic nodulations. Other Infections: The question of whether or not silicotic lungs are more' susceptible to 17.18 bacterial pneumonia than are normal lungs has been investigated. The investigating laboratories found that silicotic animals had a lower mor tality rate from pneumococcic pneumonia than did normal animals. The ex planation for this finding may lie in a more vigorous antibody response demon strated in silicotic than in normal animals. ^ < { lt 'i .. t t V-` i11 jwpjp.njaup ASARCO ELP 0005143 ' **H 19. Probably because some lung cancers are known to have arisen in pulmon ary scars, it has been suggested that there may be a greater risk for the development of cancer in silicotic lungs than in the lungs of the general popu- 1. 19 lation. However, epidemiologic studies to date have shown the opposite. Pulmonary scar cancers originate from epithelial bronchiolar or alveolar remnants imprisoned in the scars. Such remnants are not found in silicotic nodules. COALWORKERS' PNEUMOCONIOSIS Uncomplicated ("Simple*1)Coalworkers1 Pneumoconiosis and Anthracosis ("Black Lung1*); Like any of the other pneumoconioses, that occurring in coalworkers is the storage of, and tissue reaction to, dust--in this case, black dust--in the lungs. In coalworkers this black dust is chiefly coal, but in city dwellers* lungs, the black pigment may be soot or fly ash. The important feature about this form of pneumoconiosis is that the tissue reaction to the dust is minimal, hence it is classified as "benign. " Uncomplicated or ''simple1* coalworkers* pneumoconiosis is asymptomatic, but there are three important modes by which it may become complicated: first, the concomitant inhalation of significant amounts of quartz dust with the coal dust will result in collagenous fibrosis of the dust depots; a second type of com* lication is the coincidental finding of chronic obstructive bronchopulmonary disease; and a third, the association of infection with massive1 coal dust deposi- *1 tion (see PMF on page 21). In a detailed review of "Coal, " Braun tabulated findings in Bituminous Miners and Anthracite Miners in England (South Wales) and the United States calling attention to the importance of "rank" (Table 3). * Daniel C. Braun, M. D. , Assistant Medical Director, U. S. Steel Corporation. Si, T ;>i*> " ** . *1 .*$*> -s-inra** * vc.r. M ASARCO ELP 0005144 Table 3 Percentage of Workers with Modulation or Consolidation According to Length of Exposure (Comparison of Findings in South Wales and USA) Length of Exposure Under 10 years Over 20 years Length of Exposure Under 10 years Over 20 years Bituminous Miners South Wales---1938 (Hart and Aslett) 0% 3.2% Anthracite Miners South Wales--*1938 (Hart and Aslett)* 3.9% 29.0% USA--1941 (Flinn) 0% 3.2% USA--1935 (Sayers) "under 2%n 23.0% if. * Braun makes the following quote from Hart and Aslett1* work: "Hank of coal is, in fact, the most important obvious factor found to be related to the varying incidence of X-ray abnormalities among colliers at these different mines. The highest incidences were found at the anthracite and the lowest at the bituminous end of the scale of rank. " The "rank'of a coal is roughly inversely proportional to the amount of volatile matter It contains. In South Wales, anthracite coals with less than 5% volatile matter have the highest rank, and bituminous coals with over 30% volatile matter have the lowest rank. t # 1 i ASARCO ELP 0005145 21. Emphysema and Chronic Bronchitis Occurring with Coalworkers* Pneumoconiosis: Among the most common causes of breathlessness in coal miners is chronic obstructive bronchopulmonary disease. Because of the difficulty of differentia ting between symptomatic emphysema and chronic bronchitis clinically and be cause they are commonly associated, no distinction is made between them in the British medical literature. By means of thick, macrosections of coalworkers* lungs. Dr. X Cough demonstrated that the deposition of coal dust was frequently associated with focal emphysema. At first, this focal emphysema was thought to be responsible for the breathless ness observed in some coal miners; and on the basis of this assumption, the term "coalworkers1 pneumoconiosis" was sug gested to cover not only the anthracosis but also symptomatic chronic bronchitis, a common complicating finding. Since, it has been found that the focal emphysema around coal dust depots is not responsible for breathlessness. Vital statistics suggest that men who work in dusty jobs have higher death rates than those who do not. This applies to miners, foundry workers, furnace men and cotton workers, but Higgins^ has pointed to the interesting fact that in each of the above cases in which the standardized mortality ratio for an occupation is "high, " the wives of the men with high ratios also have high ratios, thus raising the important question: are the high ratios in the men attributable to occupational factors or are they due to social factors, associated with the occupation, that also affect their wives? There appears to be agreement that the emphysema responsible for the breathlessness of the coal miner is pathologically no different from that found in the lungs of the general population. A recent investigation resulted in the conclusion that not centrilobular, but panjobular emphysema was 20 responsible for the symptomatology associated with this disease. Thus, in 'sj'.t ASARCO ELP 0005146 the light of present-day knowledge, it would appear that the use of the term, "coalworkers* pneumoconiosis" as a cover for a symptomatic emphysema and chronic bronchitis is an anachronism, and erroneous: it attributes the cause of the breathlessness to coal, without mentioning the probable association with other factors* such as cigarette smoking---much more important in its etiology and aggravation to all appearances at present, ^ Infective Pneumoconiosis (Progressive Massive Fibrosis--PMF): A small, but significant, percentage of British coalworkers have developed what is recognized roentgenologically and pathologically as a progressive massive fibrosis of the lungs (PMF). This chronic condition has proved difficult to treat medically. It is often fatal, although its progress may be slow. In about a third of the cases of PMF, tubercle bacilli have been found in the lungs either by culture or by smear. 1 Although at one time it was thought that nearly all cases of PMF represented cases of tuberculo-anthracosis it is now believed that other infections may also play a role in conjunction with 6 massive dust deposits. For many years there has been controversy regarding the basic nature of PMF, another widely held concept having been that it was simply anthra silica sis. * However, with the experimental reproduction of a model of this disease (PMF) in guinea pigs, the lungs of which had been burdened with coal-mine dust and then infected with tubercle bacilli of low virulence, ' ^ the controversy tended to subside. Pathology: In simple coalworkers1 pneumoconiosis, there is multifocal black dis coloration of the pleural, as well as of the cut surfaces of the lung. As the amount of black dust deposited in the lungs increases, the foci tend to become more * ASARCO ELP 0005147 23. numerous, larger, and finally* to fuse, thereby rendering all surfaces diffusely black. Although focal emphysema is frequently present in heavily dusted lungs, this is, by no means, a constant finding. The hilar lymph nodes are usually slightly enlarged, black and firm in consistency, the last probably resulting from some degree of silica exposure in addition to the black pigment. With increasing amounts of crystalline silica dust inhaled along with the coal dust, foci of dust deposition tend to develop more collagenous i fibrous tissue and to become harder until they resemble full-fledged silicotic nodules. These nodules differ from the smooth, round, gray nodules pro duced by pure silica not only in their black color, but also in their stellate outlines and generally larger size. The nodules frequently fuse to form the Large stony-hard, black masses in the lungs characteristic of anthraailicosis. The appearance of the lungs in infective anthracosis is very similar to that of anthrasilicosis. Cavitation, when present, is usually indicative of infection. However, cavitation when found in anthracotic lungs in the absence of tuberculosis is thought to result from ischemic necrosis. Coincidental centrilobular and panlobular emphysema found in pneumoconiotic lungs of coal workers is very similar to the emphysema found in lungs free of excessive amounts of black pigment. General Considerations: Estimating Prognosis by X-Ray--PMF-- In Coal Workers--Dra. P. D. Oldham and C. E. Rossiter^'^ recently have confirmed the opinion of Dr. A. L. Cochrane that the size of the conglomerate lesions in PMF was, of prognostic value in estimating reduced life expectancy. They find that size of PMF and residual volume correlate best with fatal outcome, while clinical evidence of abnormal physiological dynamics were of much less value in such a prediction. Radiographic findings thus continue to be of prime importance to chest physi cians attending cases of PMF. T ASARCO ELP 0005148 r i4. ASBESTOSIS There are three commonly used types of asbestos. * In this country, about 95% of the asbestos used is chrysotile, mined in Canada. The other two types, used largely for insulation and composite materials, are amosite and crocidolite which come mostly from South Africa. Whereas in the asbestos textile industry the worker's exposure to mineral dust is Limited practically to chrysotile. in other segments of the asbestos industry the dust exposures are usually mixed. Not only are the workers in this industry usually exposed to more than one kind of asbestos dust, but also to other dusts as well. It is common, for instance, to find cement and quartz dust associated in various proportions with asbestos dust. The tissue reaction to the dust may accord ingly be modified depending upon the nature and amounts of the associated dusts in the lungs. The older literature contains many references to the dictum that only asbestos fibers lOp or longer are pathogenic, that the short-fibered asbestos dust does not cause asbestosis. Experimental studies have failed to support this concept. According to Smith, "pulmonary fibrosis resulting from prolonged inhalation of asbestos fiber will produce a typical X-ray pattern. In early, or first-stage asbestosis, the X-ray shows a fine diffuse homogeneous infiltra tion throughout both lower lung fields. It should be noted that this infiltration is bilateral, that it is generalized at both bases, and that the nodular or con glomerate patterns of other pneumoconioses, such as silicosis, are not seen in asbestosis. There is a considerable amount of pleural reaction associated * Smith, Kenneth W. , M. D. , then Medical Director, Johns-Maziville Corporation, presently, Medical Director, Brush Beryllium Company. HgTV J W* ASARCO ELP 0005149 25. with this disease, which may account for the 'ground glass' pattern which has been used to describe the typical X-ray picture. . .In moderately advanced, or second-stage, asbestosis, the infiltration has increased but still is confined to the lower lung fields. The 'ground glass' pattern is more apparent, and the heart borders are becoming indistinct or shaggy. There is some irregularity of the diaphragmatic outlines and be ginning obliteration of both the cardiophrenic and the costophrenic angles. "In far-advanced, or third-stage, asbestosis, the infiltration still is homogeneous and bilateral, has spread to the middle and possibly the upper portion of the lung fields, but the apices remain clear. The cardiac outline is almost completely obliterated, as are the domes of the diaphragm and the costophrenic sulci. With this picture in mind, it is advisable to reiterate the observations of many physicians, namely, that the X-ray picture should never be used to estimate the presence or the extent of impaired pulmonary function or disability. Many cases with X-ray evidence of third-stage asbestosis have been known to carry on their usual work and live fairly comfortable lives for several years. On the other hand, no case of definite disability has been seen unless there was the typical X-ray pattern of asbestosis. X-ray changes typical of asbestosis seldom are seen unless there has been a period of at least ten years of continuous exposure. . .In some cases it has been suggested that the appearance of calcified pleural plaques on the X-ray, coupled with a potential exposure to asbestos fibre are pathognomonic of asbestosie. Reviewing a quarter century of serial X-ray films, the author noted calcified pleural plaques appeared rarely in several thousands of workers in an asbestos mine in Canada. The fibre from ASARCO ELP 0005150 26. this mine has been used for a great many years in numerous American plants. Cases of asbestosis have occurred in this mine and in these plants, but in only one of the plants is there any evidence of pleural plaque formation. If inhala tion of the asbestos fibre alone could cause these plaques, one would expect to find plaques wherever the fibre is used. In view of the above-mentioned evidence the causal relationship of pleural plaques to other pulmonary and other cardiac conditions in addition to asbestosis is worthy of investigation. . .There is no typical clinical picture for asbestosis. The disease is insidious in its onset and slowly progressive with continued inhalation of the fibre. There is a gradual increase in cough and expectoration, some anorexia and weight loss, then slowly increasing dyspnea. Cyanosis and clubbing of the fingers are rare findings."*' It is important to note here that attempts should not be made to transfer the above findings, which relate to asbestos exposure, to workers exposed to mixed dusts: admixture of other dusts, such as silica, may greatly affect the appearance of the X-ray and also the histopathological findings. For a discussion of mixed dust exposure see page 6. Guidelines for X-ray interpretation in asbes tosis are being developed by the U. S. Public Health Service 2 (see page 9). Unlike most pneumoconioses, which are multifocal in character, asbestosis involves alveolar walls diffusely. Nevertheless, in the experimental ; animal--and it has also been claimed for human asbestosis--the disease is initially also multifocal, each focus being centered in the* proximal portion of the primary lobule, the respiratory bronchiole. When the disease is active, as it is shortly following the deposition of the dust in the lung, the alveolar walls become thickened by cohesive proliferated ASARCO ELP 0005151 27 cells that are supported by argyrophilic fibers. This is the florid stage. With timer usually measured by many years* the septa lose their cellularity and the argyrophilic stroma becomes converted into adult collagen. This finding indicates the inflammation had healed. In healing* however, the septum frequently be comes avascular and stiff. The involvement from one alveolus to the next may not be uniform. Some severely thickened collagenous alveolar walls have shown an almost angioma-like plethora of capillaries on one or both surfaces of the dense and acellular collagen. This has been a not uncommon finding in ashestotic lungs after the patient has been subjected to prolonged exposures to high oxygen concentrations prior to death. The uncomplicated* healed asbestotic lungs are small* stiff lungs* presumably because of the widespread contracture of the collagen in the alveolar septa. Complications: Ope of the more common coincidental findings encountered in asbestotic lungs is chronic obstructive bronchopulmonary disease. Claims for a causeand-effect relationship have frequently been made when emphysematous changes have been found associated with asbestosis. As with the other pneumoconioses, these claims have not been adequately supported in fact. More epidemiologic studies and data regarding the pathogenesis of emphysema are needed* however, to exclude any possible cause-and-effect or aggravating relationships. Another complication associated with asbestotic lungs that has received much attention is a pleural fibrosis that may attain a thickness of one centi meter or more and the consistency of shoe leather. Not infrequently, the pleural inflammatory fibrous tissue becomes calcified* forming pleural plaques. As with other findings, the inevitable question has arisen whether or not the i r ASARCO ELP 0005152 r 28. association represents a cause-and-effect relationship. The main obstacle in the path of acceptance of such relationship is the fact that it has not been possi ble to show a relationship between the thickened pleura and the physical presence of the dust. If asbestos dust were responsible for the thickened fibrotic pleura* one would expect to find the specific pathogenic dust concentrated there just as one finds quartz dust concentrated within silicotic nodules. Not only is there no concentration of asbestos dust, but no dust of any kind is demonstrable in the thickened pleura with the optical microscope. An occasional asbestos body has very rarely been found in such pleural lesions. A recent extensive epidemio logic investigation of calcific pleural plaques in Finland has shown that these occur in population groups living in communities containing asbestos mines and mills with a prevalence that is not significantly higher than the prevalence of pleural plaques in stable rural communities that do not have asbestos mines or mills. This observation effectively supports the opinion of Smith* that if asbestos exposure alone were able to produce pleural plaques, it should be found wherever asbestos is inhaled, which is not the case. Two types of cancer have been associated with the inhalation of asbestos i dust, carcinoma of the lung and mesothelioma of the pleura or peritoneum. Both kinds of malignant tumors have been produced in experimental animals by the inhalation or injection of asbestos dust. Epidemiologic studies have convincingly demonstrated a much higher prevalence of pulmonary carcinoma among British i asbestos textile workers who had been exposed to asbestos dust prior to 1935 than -i A among the general population. However, Knox et al have shown more recently that in the thirty-odd years since the British asbestos textile plant concerned i ASARCO ELP 00051 S3 29. instituted good housekeeping measures, the risk of developing lung cancer among its workers has not been higher than that of the general population. Smith* in 1963 reviewed his L8 years of experience in the American asbestos industry and gave his impression that among workers exposed to chrysotile fiber, there were no more cases of pulmonary malignancy than among the general population. The current status of bioeffects research on asbestos was the subject of meetings sponsored recently by the New York Academy of Science2^ and In dustrial Hygiene Foundation. ^ Epidemiologic studies have shown a much higher prevalence of pleural and peritoneal mesotheliomas among those exposed to asbestos dust than among the unexposed general population. Although most of the former were workers exposed to mixtures of different kinds of asbestos dust, reports from South Africa indicate that non-occupational (but equally heavy) exposure to the crocidolite type of asbestos was incriminated in the pro duction of mesotheliomatous tumors with a delay of an average of about 43 years before appearance of the tumors, in which evidence of asbestosis was absent or minimal. In other cases reported from the United States, the possibility that the workers inhaled sufficient crocidolite dust to have been a factor in the meso thelioma production could not be ruled out; further and more careful epidemio logical studies are needed to determine if exposures associated with types of asbestos other than crocidolite may produce mesotheliomas in man. Asbestos Bodies Versus Ferruginous Bodies; ,, The hallmark of an asbestotic pulmonary inflammation is the presence of asbestos bodies. These are golden brown symmetrical, elongated structures composed largely of ferritin, or ferritin-like iron-containing proteins, pre cipitated around a central transparent or translucent filament. They are often ASARCO ELP 0005154. 30. segmented and have clubbed ends. They measure l-3p in diameter and 20y. or more in length. In the lungs, they are usually found free in the air spaces, often in clusters. Shapes and sizes vary greatly. In recent years these iron-containing, or ferruginous bodies have been found at autopsy in the fluid expressed from the lung9 in 30 to 48% of the gen eral population in Capetown. South Africa; Miami, Florida; Pittsburgh, Zh, 27 Pennsylvania and Montreal, Canada. The lungs in which these bodies have been found generally did not exhibit significant disease. 'Attempts have been made to link the finding of the so-called "asbestos1* or ferruginous bodies to an assumed widespread pollution of urban atmospheres with asbestos dust on the assumption that the formation of ferruginous bodies is a specific reaction to the presence of asbestos fibers; however, recent investigations have demonstrated that filamentous dusts other than those of asbestos may also evoke the formation of ferruginous bodies. One of these filamentous dusts 28 producing such bodies in the lungs of hamsters is aluminum silicate. $ 9 ASARCO ELP 0005155