THE DUST CONTENT OF THE LUNGS OF HARD-ROCK MINERS AND ITS RELATIONSHIP TO OCCUPATIONAL EXPOSURE, PATHOLOGICAL AND RADIOLOGICAL FINDINGS

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1 Ann. occup. Hyg., Vol. 6. Nos. -4. pp OO-4878/8/OO4O-O9SO.O Primed in Great Britain. Pergamon Press Lid. Inhaled Particles V i 98 British Occupational Hygiene Society. THE DUST CONTENT OF THE LUNGS OF HARD-ROCK MINERS AND ITS RELATIONSHIP TO OCCUPATIONAL EXPOSURE, PATHOLOGICAL AND RADIOLOGICAL FINDINGS D. K. VERMA, D. C. F. MUIR, M. L. STEWART, J. A. JULIAN and A. C. RlTCHIEf Occupational Health Program, McMaster University, Hamilton, Ontario, Canada f Department of Pathology, University of Toronto, Toronto, Ontario, Canada Abstract A study is being undertaken to investigate the dust content of the lungs of deceased miners of Ontario, Canada. The preliminaryfindingsinvolving eight sets of lungs were described. Radiology, pathology, dust analysis, size distribution and hydroxyproline determinations were made. Relationships between dust composition and degree offibrosis,as indicated by hydroxyproline, have been examined. The retained lung dust, when compared with the occupational exposure, appeared to indicate preferential enrichment of silica in the lung. The hydroxyproline content in the lung was found to correlate well with the non-silica inorganic portion of lung dust. INTRODUCTION THE RELATIONSHIP between lung dust content and associated lung pathology is fundamental to an understanding of the quantity and composition of airborne contaminants which produce clinical disease in exposed workers. Equally, it is important to identify those dust levels or dust compositions which are not associated with lung disease, since this may be of considerable assistance in defining safe working conditions. There have been a number of reports concerning the dust content of the lungs of deceased coal workers and its relationship to radiological, pathological and physiological findings (KING and GILCHRIST, 945; RIVERS et al, 96; CARTWRIGHT and NAGELSCHMIDT, 96; LEITERITZ et al, 967; CARTWRIGHT, 967; ROSSITER et al, 967; CASSWELL et al, 97; SWEET et al, 974; DAVIS et al, 977). In contrast there have been few studies concerning the dust content of the lungs of hard-rock miners or of other occupational groups with somewhat similar environmental exposures, e.g. foundry workers. (STRECKER and EINBRODT, 96; DOBREVA et al, 977). There is a unique opportunity to study the effects of inhaled quartz in Ontario, because all workers exposed to dusts containing silica have had annual chest radiographs for many years and, more recently, have also had annual measurements of ventilatory capacity. The present paper presents preliminaryfindingsin eight deceased hard-rock miners from an on-going investigation into the relationship between the post-mortem lung dust content and radiological, physiological and occupational data. Downloaded from at Pennsylvania State University on April 8, 6 4

2 4 D. K.. VERMA et al. MATERIAL The lungs of eight cases were selected from among those referred to one of us (A. C. R.) either by the Workmen's Compensation Board of Ontario for the adjudication of a silicosis compensation claim or at the request of the next of kin to determine if there was silicosis present in those instances where the radiographs had been normal during life. Cases selected in this way are clearly not representative of all deceased Ontario miners. However, because of the tendency in the mining community to request post-mortem information in case it should support a compensation claim, we were able to obtain a broad range of cases including those with normal radiographs as well as those with obvious silicosis. Table gives details of the cases selected. As noted above, these miners had undergone routine medical examinations including radiographs of the chest since they started mining. Some information on their occupational exposures is available. However, accurate, full-shift exposure estimates are not available, because dust levels in the past were measured by a konimeter. Gravimetric dust sampling techniques are now used and it may be possible to estimate the previous dust exposure in due course. Case Age first exposed TABLE. POPULATION Age at death Nickel miner, all others gold miners. (Occupation) Underground Trackman Driller Machine runner Stope/shift boss Stope/timber Shift boss Loader/timber Years of exposure METHODS Introduction The eight pairs of lungs were received after fixation in formalin, but had not been inflated. Each of the 6 lungs was cut transversely into three approximately equal sections. All analyses (radiology, pathology, dust content, particle size measurement, hydroxyproline determination) were carried out on each of the 48 sections. The decision to divide each lung into three sections by horizontal cuts rather than on a lobar basis was based on three considerations:first, radiographs for silicosis are traditionally classified by three zones; second, silicosis often appears on a zonal basis and may be confined to the upper part of the lung; third, the approach has some physiological relevance, since blood-flow and ventilation'of the lung are gravity dependent and vary from the lower to the upper zones Downloaded from at Pennsylvania State University on April 8, 6 Radiology and pathology The last X-ray taken before the death of each case was classified according to the extended ILO classification (97). In this preliminary study films were classified by

3 Dust content of the lungs of hard-rock miners 4 only one reader (D. C. F. M.). The radiological grading was performed without prior knowledge of the pathological findings. Each case was examined in detail by a pathologist (A. C. R.). For this study, the degree of pulmonary silicosis in each section was graded on an arbitrary 4 point scale, with '' representing normal and '' representing severe silicosis. Dust and hydroxyproline analysis After pathological examination about 99% of the tissue of each lung was available for the dust analysis. The hilar lymph nodes were dissected out and stored for future examination. Each section of the lung was cut into small to \ in. square pieces, dried with absorbent paper and weighed. The pieces were transferred into a heavy-duty blender and an appropriate amount of water was added, usually in the ratio of : to : water to tissue. The tissue was homogenized, then transferred intoflasksand freezedried. The dry lung homogenate was stored in polyethylene bottles and aliquots were ground in a Spex mixer mill for further analysis. The procedure employed to recover the dust from the ground lung was essentially the hydrochloric acid digestion method reported by GUEST (976). The total dust so recovered was ashed in a low temperature plasma asher to determine the inorganic dust. Organic dust was calculated by subtraction. The inorganic portion of the dust was then used for crystalline silica (quartz) determination and to obtain the particle size distribution. Silica was determined by the infrared spectrophotometric method (NIOSH, 977). The non-silica inorganic portion of the dust was calculated by subtraction. All analyses were performed in triplicate with appropriate corrections for the moisture content. Volume size distributions of the inorganic dusts were determined using a Coulter counter Model 'B'. The hydroxyproline content (HP) was assayed as an index of the amount of collagen. The analysis was carried out essentially by the method of BERGMAN and LOXLEY (969). RESULTS In Table, the dust and hydroxyproline measurements are expressed as the absolute amount within each lung, and not as milligrams per gram of dry lung tissue. Results are not reported for lungs where lobectomies had been performed. The radiological and pathological gradings for each section are given in Table. The relationship between the scores displayed in Fig. demonstrates good statistical agreement (Kappa =.47, p<.). The strength of the association between the dust components and hydroxyproline was measured by product-moment correlations. In Table 4, the correlation coefficients for the relationships of interest are displayed for the 48 sections, 6 lung specimens, and eight cases. With a small sample of only eight cases, correlations would need to be as high as.69 to be statistically different from zero (a =.5). Furthermore, correlation coefficients are generally unreliable for small samples. Only the silica to non-silica and HP to non-silica comparisons achieve this level. If we assume that lungs from the same individual are independent of each other, we can correlate 6 pairs of observations and reject the hypothesis of zero correlation where the sample correlation coefficient Downloaded from at Pennsylvania State University on April 8, 6

4 44 D. K. VERMA et al. TABLE. DUST AND HYDROXYPROLINE: TOTAL AMOUNTS PER LUNG Case Lung weight ( g) Left Right Total dust (mg) Left Right Left Silica (mg) Right Non-silica (mg) Left Right Hydroxyproline (mg) Left Right Lobectomy performed. Case No Score Tuberculosis present TABLE. RADIOLOGICAL AND PATHOLOGICAL SCORE Top / /4 PMF / o/. / / / / / / / / / /4 PMF Left lung Middle / / / / Lung sections Bottom / / PATHOLOGICAL SCORE (4) () () ' Top / /4 PMF / / Right lung Middle / / / / / Bottom / / / / Downloaded from at Pennsylvania State University on April 8, 6 FIG. I. The relationship between the radiological and pathological score for each lung section.

5 Dust content of the lungs of hard-rock miners 45 TABLE 4. CORRELATION COEFFICIENTS Per case (8) Per lung (6) Per section (48) Silica vs non-silica Hydroxyproline vs silica Hydroxyproline vs non-silica Hydroxyproline vs total dust Hydroxyproline vs organic Significant at 5% level. Significant at % level. exceeds.5. From Table 4, silica correlates well with non-silica (r =.84, p <.), and the correlations between HP and non-silica (r =.68, p<.) and HP and total dust (r =.6, p<.5) are significant. If we make the stronger assumption that sections within the same lung and individual react independently, then 48 sets of measurements are available. In this case, a correlation greater than.8 is considered significantly different from zero. Again, in Table 4, we find highly significant correlations (p <.) for all of the relationships. Plots of HP against total dust, organic dust, silica and nonsilica are displayed in Fig.. The silica to non-silica relationship, shown in Fig., is well defined by a straight line through the origin with a non-silica to silica ratio of :. This ratio also holds on a per lung and case basis. In Fig. 4, hydroxyproline levels are plotted against radiological and pathological scores. The means, as indicated by the horizontal bars, suggest a gradient of fibrosis (graded radiologically or pathologically) in relation to hydroxyproline content, but the Downloaded from at Pennsylvania State University on April 8, HYDROXYPROLINE (mg) FIG.. The relationship between the amount of hydroxyproline and the amount of (A) total dust, (B) organic dust, (C) silica, (D) inorganic non-silica in each section.

6 46 D. K. VERMA et al NON-SILICA Img) FIG.. The relationship between the amount of silica and the amount of non-silica inorganic dust present in each section. i i T RADIOLOGICAL SCORE PATHOLOGICAL SCORE FIG. 4. The relationship between the radiological/pathological score and the amount of hydroxyproline present in each section. most obvious difference is the degree of scatter in the normal sections as compared with the abnormals. A volume size histogram of inorganic dust for a typical section is shown in Fig. 5. The diameter in micrometers is plotted on a natural logarithmic scale to give intervals of equal size ratios. Truncation occurred at a minimum diameter of.6 /im (.5 on a log scale) because of limitations of the instrument. In Fig. 5, the modal volume occurs at.88 fim (-. on a log scale). The dust exposure of the cases analysed is difficult to estimate accurately, because dust measurements in the past in these mines were carried out by konimeter. However, the results of recent gravimetric surveys conducted in the gold mines indicate the respirable dust to average. mg m" (range.9-4. mgm" ) and the silica to average 9% (range -%) of the respirable fraction by weight (ONTARIO MINISTRY OF LABOUR, 979). The silica content of the lungs was 4%, on average (Table 5), so that there was apparently some preferential retention of silica in the lungs. Downloaded from at Pennsylvania State University on April 8, 6 DISCUSSION The method of analysing lungs by section appears to offer considerable advantages. Because the effects of silicosis may vary greatly between one region of the lung and another, there are potential sources of bias if the pathology and radiology are simply

7 Dust content of the lungs of hard-rock miners g -.. > - - I i I r I I i T i I In DIAMETER l im FIG. 5. A typical volume size distribution of inorganic dust found in the lung. Silica (%) Non-silica inorganic (%) Organic (%) TABLE 5. DUST COMPOSITION Lung Average Range Mine Average Range averaged throughout a given lung. Our method has the disadvantage that it was not possible to divide the lung into sections of equal size, since the tissues were fixed by varying methods and were of irregular shape. The sections do not correspond to any clear anatomical division nor are they exactly comparable to the regions seen on a radiograph. Despite these limitations, the method presents a logical solution to a difficult methodological problem. Expression of the dust and hydroxyproline content of each section in absolute amounts is subject to possible errors resulting from uneven sectioning of the lung. However, it avoids the more fundamental bias introduced by relating dust contents to unit weights of dried lung tissue, because these cannot be considered as independent variables. The results confirm important findings reported by previous investigators. For example, the size distributions of the retained dusts were remarkably similar to those reported in coal workers by CARTWRIGHT and NAGELSCHMIDT (96), although the environmental exposures were almost certainly very different. There was good correlation between radiology and pathology, as was found in the case of coal miners by ROSSITER et al. (967). The relationships of hydroxyproline with total respirable dust, organic dust, silica dust and non-silica dust suggests that total dust or non-silica inorganics might turn out to be equally as good as silica at indicating the fibrogenic potential of environmental dust. Unfortunately, silica and non-silica inorganic dust in our samples were so strongly correlated that it is difficult to analyse their effects separately. When further analyses of lung specimens from workers in low and high quartz mines (e.g. nickel and uranium mines respectively) are available, it may be possible to separate the silica and non-silica inorganic effects. - Downloaded from at Pennsylvania State University on April 8, 6

8 48 D. K. VERMA et al. When the composition of the retained lung dust is compared with that estimated to be in the airborne respirable mine dust, there appears to be greater proportional retention of silica. This enrichment of silica in the lung has also been noted by DAVIS et al. (977) and LEITERITZ et al. (967) in coal miners. There are few studies in hard-rock miners with which the data can be compared DOBREVA et al. (977) reported levels of total dust in one lung of hard-rock tunnel workers and uranium miners etc. to range between.6 and g (mean =., median = 8.65). One of the most striking aspects of our data was the low level of total dust and silica (.4 and.4 g) found in both lungs that appeared to be associated with undoubted radiological and pathological evidence of pneumoconiosis in contrast with the much higher dust burdens commonly found in the lungs of coal workers. The low level of total dust found in our specimens presumably reflects a relatively low level of airborne dust in Ontario gold mines, although it must not be forgotten that the men were elderly and had not worked underground for some years. Slow clearance of dust from the lung presumably continued throughout their years of retirement. However, there seems little doubt that a given mass of dust in the lungs of hard-rock miners is morefibrogenicthan an equivalent weight of dust in the lung of a coal miner. Paradoxically, the composition of the coal mine dust does not appear to be directly related to its toxicity (WALTON et al., 975). One aspect that has caused us much thought, is the fact that aluminium powder by inhalation has been used in Ontario gold mines since 944 with the objective of preventing silicosis. The practice has only been discontinued since 98. The cases reported here have almost certainly inhaled aluminium in this way. We hope to study this problem by examining the lungs of silicotic workers from foundries, since prophylatic aluminium inhalations have never been used in these industries. Acknowledgements The authors would like to thank Mr Denis Grant who did much of the initial development work. We are also grateful to the Workmen's Compensation Board of Ontario for their assistance and to the Ministry of Labour of the Government of Ontario for financial support. REFERENCES BERGMAN, I. and LOXLEY, R. (969) Lung tissue hydrolysates: studies of the optimum conditions for the spectrophotometric determination of hydroxyproline. Analyst 94, CARTWRIGHT, J. and NAGELSCHMIDT, G. (96) The size and shape of dust from human lungs and its relation to relative sampling. Inhaled Panicles and Vapours (Edited by DAVIES, C. N.) pp , Pergamon Press, Oxford. CARTWRIGHT, J. (967) Airborne dust in coal mines: the particle-size-selection characteristics of the lung and the desirable characteristics of dust-sampling instruments. Inhaled Particles and Vapours II (Edited by DAVIES, C. N.) pp. -48, Pergamon Press, Oxford. CASSWELL, C, BERGMAN, I. and ROSSITER, C. E. (97) The relation of radiological appearance in simple pneumoconiosis of coal workers to the content and composition of the lung. Inhaled Particles III (Edited by WALTON, W. H.) Vol. II, pp. 7-76, Unwin Brothers, Old Woking, Surrey. DAVIS, J. M. G., OTTERY, J. and LE ROUX, A. (977) The effect of quartz and other non-coal dusts in coalworkers' pneumoconiosis. Part II. Lung autopsy study. Inhaled Particles IV (Edited by WALTON, W. H.) Part II, pp. 69-7, Pergamon Press, Oxford. DOBREVA, M., BURILKOV, T., KOLEV, K. and LALOVA, P. (977) Characteristics of lung dusts and their relation to dust exposure and pathologicalfindingsin the lungs. Inhaled Particles IV (Edited by WALTON, W. H.) Part II, pp , Pergamon Press, Oxford. GUEST, L. (976) The recovery of dust from formalin-fixed pneumoconiotic lungs: a comparison of the methods used at SMRE. Ann. occup. Hyg. 9, Downloaded from at Pennsylvania State University on April 8, 6

9 Dust content of the lungs of hard-rock miners 49 KING, E. J. and GILCHRIST, M. (945) Chronic pulmonary disease in South Wales coalminers-iii. Experimental studies, the estimation of coal and of aluminium in dried lungs. Med. Res. Council Spec. Rep. 5, -8. LEITERITZ, H., EINBRODT. H. and KLOSTERKOTTER, W. (967) Grain size and mineral content of lung dust of coal miners compared with mine dust. Inhaled Particles and Vapours II (Edited by DAVIES, C. N.) pp. 8-9, Pergamon Press, Oxford. NIOSH (977) Quartz in Coal Dust by Infrared Spectroscopy: Manual of Analytical Methods. Vol., P&CAM. ONTARIO MINISTRY OF LABOUR (979) Ontario Gold Mine Survey. Ontario Ministry of Labour, Toronto, Ontario. RIVERS, D., WISE, M. E., KING, E. J. and NAGELSCHMIDT, G. (96) Dust content, radiology and pathology in simple pneumoconiosis of coalworkers. Part I: General observations. Br. J. Ind. Med. 7, ROSSITER, C. E., RIVERS, D., BERGMAN, C, CASSWELL, C. and NAGELSCHMIDT, G. (967) Dust content, radiology and pathology in simple pneumoconiosis of coalworkers (Further Report). Inhaled Particles and Vapours II (Edited by DAVIES, C. N.) pp , Pergamon Press, Oxford. STRECKER, F. J. and EINBRODT, H. J. (96) Uber Die Staubablagerung In Der Lunge Und Den Regionalen Lymphknoten (Untersuchungen An Menschlichem Material), Inhaled Particles and Vapours (Edited by DAVIES, C. N.) pp , Pergamon Press, Oxford. SWEET, D. V., CROUSE, W. E., CRABLE, J. V., CARLBERG, J. R. and LAINHART, W. S. (974) The relationship of total dust, free silica and trace metal concentrations to the occupational respiratory disease of bituminous coal miners, Am. Ind. Hyg. Ass. J. 5, WALTON, W. H., DODGSON, J., HADDEN, G. G. and JACOBSEN, M. (975) The effect of quartz and other noncoal dusts in coalworkers' pneumoconiosis Part I: Epidemiological studies. Inhaled Particles IV (Edited by WALTON, W. H.) Part II, pp , Pergamon Press, Oxford. DISCUSSION C. E. ROSSITER: () The author has indicated that each pair of lungs is being divided into six parts for the chemical and pathological assessments. However, the author proposed to consider each part as independent in the statistical analysis. Not only is this an improper assumption about the six parts for each individual, but also it is throwing away potentially valuable information about individual susceptibility. Such information is not available elsewhere, and this ought to be a major aim of this study. () It was reported that the ILO 97 Classification of Radiographic Appearances of Pneumoconiosis was used. This does not provide for the separate assessment of profusion of small opacities in each of the six zones. Please would the author indicate how it is intended to produce separate profusion values for correlation with the chemical and pathological variables. Dr VERMA: We are certainly taking care to ensure that information is not lost. The advantage of analysing sections of the lung separately results from the uneven distribution of fibrosis in the lungs of workers with silicosis. In addition, we will certainly be looking at the within-person as well as the between-person relationships, but there are too few cases in the present data to draw conclusions at this stage. Regarding the radiology, you are correct in stating that the 97 classification requires the results to be presented as an overall level of silicosis. What we did was to read each zone separately as if it was an independent section of the lung. This is, of course, what is specified in recent editions of the classification. At the time these films were read we did not have the 98 films and were simply using the earlier standards as our reference point. Downloaded from at Pennsylvania State University on April 8, 6

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