Document wRqG1X9BkgYNrDEx5KpQXd4B

FILE NAM E: Talc (TALC) DATE: 2002 DOC#: TALC023 DOCUMENT DESCRIPTION: Journal Article - M esotheliom a among W orkers in Asbestiform Fiber-bearing Talc M ines in NY State Ann. occup. Hyg,, Vol. 46, Supplement 1, pp. 132-135.2002 2002 British Occupational Hygiene Society Published by Oxford University Press DOl: 10.!093/annhyg/mef651 Mesothelioma among Workers in Asbestiform Fiber bearing Talc Mines in New York State MINDY J. HULL1, JERROLD L. ABRAHAM1* and BRUCE W. CASE2 'State University o f New York, Upstate Medical University, Pathology, Syracuse, NY 13210, USA; 2School of Environment, McGill University, Montreal, Canada Asbestos-related disease among talc miners and millers in a group of mines in two counties of northern New York State has been noted and disputed since the 1930s. One o f the two counties was identified as among the 10 in the USA with the highest mesothelioma mortality up to 1981 for both men and women. Eight talc miners had been identified in previous studies as having mesothelioma. In the current study we: (i) report five new cases of mesothelioma among talc workers; (ii) present the results of and demonstrate the similarity between lung fiber burden analyses for selected cases and controls; and (iii) update mesothelioma mortality in this district using demographic and cause of death cancer information from 1950 to 1997. Our results indi cate that New York talc exposure is associated with mesothelioma, and deserves further public health attention. Keywords: mesothelioma; talc; pathology; epidemiology; mortality; scanning electron microscopy; asbestos BACKGROUND In 1878 talc mining introduced an economic boon to the rural agricultural counties of St Lawrence and Jefferson in northern New York State. The hub of this industry was Gouvemeur, home of several talc mines, at least one of which is still operational. We believe that occupational exposure to dust from the talc mines and mills caused the mesothelioma excess in these counties. We support this by examining the similarity between the lung fiber burden of talc miners with and without mesothelioma, and deter mining the presence or absence of retained fibers indicative of commercial amphibole asbestos expos ure. There are at least eight histologically confirmed cases of mesothelioma among New York State talc miners and millers reported as of 1986, and increased pleural mesothelioma mortality in Jefferson County. Here we report five new mesothelioma cases and epidemiological data to determine if this trend continues. In the 1930s Merewether (1930) and others begin to describe asbestos exposure and its role in fibrotic lung disease. Pathology related to talc exposure also was being investigated, with a reported range of lung findings from nodular, silicosis-like to diffuse, Author to whom correspondence should be addressed. Department of Pathology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. asbestos-like patterns (Porro et a l, 1942). By 1943, Siegal and co-workers were studying New York State talc miners and millers (Siegal et al., 1943). They described the mined talc `of a fibrous variety.. .with it is found tremolite.. .a similar appearing mineral occur ring in a fibrous or asbestiform state which... changes over to talc'. Midget impinger concentrations of particles ranged from 6 to 5000 million particles per cubic foot (mpef) in mining and from 20 to 215 mpef in milling. They found evidence of marked pulmon ary fibrosis on chest roentgenograms in 32, all of whom had a >10 yr exposure history, out of a total of 221 talc workers. This established a clear relationship between lung fibrosis and duration of talc exposure. Fourteen of these workers also had pleural plaques, providing the first documentation o f `talc plaques'. In 1967 Kleinfeld et al. documented 9/220 talc workers with lung cancer; this represented a >4-fold excess. In addition, the first pleural `fibrosarcoma' and peri toneal mesothelioma in talc miners were described in this cohort. Vianna et al. (1981) conducted an inci dence study of all histologically confirmed mesos in New York State between 1973 and 1978. They found that Jefferson County had a mesothelioma rate twice that of the rest of the state. A total of six cases of mesothelioma (four male, two female) occurred in talc miners. Enterline and Henderson (1987) also concluded a mesothelioma excess in Jefferson County after looking at national mesothelioma incidence by county from 1968 to 1981. They observed four cases in 132 Mesothelioma in asbestiform fiber-bearing talc mines 133 Table 1. Diagnosis and immunohistochemical results (where applicable) of three mesothelioma cases Case I Case 2 Case 3 Case 4 Case 5 Description of pleural mesothelioma Biphasic, diffuse Sarcomatous Epithelial, with rare biphasic areas Diagnosis of mesothelioma made by New York State Worker's Compensation Board. No tissue available Diagnosis of mesothelioma made by death certificate. No tissue available Immunohistochemistry Pan-cytokeratin (+++), calretinin (+++) Cytokeratin (+++), calretinin (-) CEA (-), alcian blue (+ cellular), mucicarmine (+ rare focal) (+-W-) strongly positive; (+) weakly positive; (-) negative. Table 2. Pertinent data from New York talc miners diagnosed with malignant mesothelioma Case Birth Death Smoking Relevant occupation(s) in the talc industryh history3 First year on job 1 1931 1989 10 Mucker, driller, Hardinge operator 1952 2 1937 1990 0 Packed talc into trucks 1955 3 1912 1984 0 Mechanical engineer--helped construct two talc mines Unknown 4 1923 1981 Unknown Unspecified employment at a single talc company 1953 5 1925 1994 Unknown Roustabout, foreman, packhouse worker 1949 aln pack-yr (no. of packs per day x no. of yr smoking), includes all known dusty jobs (talc or otherwise). Job duration (yr) 22 4 2 22 25 females (0.6 expected), and seven cases in males (1.4 expected). This gave Jefferson County the second and sixth highest mortality rates from mesothelioma for females and males, respectively, in the USA. METHODS AND RESULTS Subjects The SUNY Upstate Medical University serves the catchment area of Jefferson and St Lawrence counties. From 1984 to 1987, 36 biopsy and/or autopsy samples were recovered from talc workers with lung disease. Hospitalization, employment and (when applicable) death information were collected. From the 36 miners, five mesothelioma cases were documented. For three of these, the diagnosis of mesothelioma was histologically and immunohistochemically confirmed using hematoxylin & eosin, alcian blue, mucicarmine, calretinin, carcinoembryonic. antigen (CEA) and cytokeratin staining (see Table 1). Case 1 is described in detail as a represent ative clinical course of mesothelioma. Table 2 contains demographic data for the five mesothelioma cases. Observed and expected pleural mesothelioma mortality in mining counties Calculations of mortality were performed at the University of Pittsburgh using the same protocol as that described by Enterline and Henderson (1987). Observed and expected values were updated to include the most recent years available (overall, from 1968 to 1997). Figure la,b presents the mesothelioma mortality for males and females, respectively. (a) 2.5 2.0 1.5 1.0 0.5 0.0 1965- 1970- 1975- 1980- 1985- 1990- 1995- (b) 1965- 1970- 1975- 1980- 1985- 1990- 1995Fig. 1. Yearly mesothelioma mortality rate per 100000 (a) males and (b) females. Lung-retained particulate andfiber analysis Lung parenchyma from two mesothelioma cases and eight non-mesothelioma cases was available for analysis. The non-fibrous inorganic particulate lung 134 M. J. Hull, J. L. Abraham and B. W. Case burden was measured using morphometric in situ analysis of tissue sections (Abraham and Burnett, 1983). For fiber analysis, lung tissue was digested with sodium hypochlorite and the residue collected on polycarbonate filters for analysis of asbestos bodies by light microscopy or fibers by scanning elec tron microscopy/energy dispersive X-ray spectros copy (Abraham et a l, 1991). The analytical results are displayed in Table 3. For fibers >1 pm, length, width and chemistry were recorded. Log normalized lengths and widths of the fibers found in the meso thelioma cases and the non-mesothelioma cases were compared using Student's r-test (Analyze-It Soft ware, Ltd). Significance was defined as P < 0.05. Finding no difference between dimensions of each fiber type would support similar dust exposure between miners with and without mesothelioma. Case 1 illustrates a representative medical history. This was a 43-yr-old, 5'8", 190 lb, white, hyper tensive male, with a 10 pack-yr smoking history who presented in 1974 with `hardness of breathing' for 4--5 yr. He reported nocturnal wheezing, per sistent anterior chest pressure, chronic cough (1 oz daily sputum), occasional hemoptysis, and difficulty walking -200 m. He had a 22 yr talc dust exposure history, working at times as a mucker, driller and HardingeTM operator at two New York talc mines. He had optional access' to a respirator that proved too cumbersome to work with. Both his father (now deceased) and brother had been diagnosed with talc pneumoconiosis. His physical examination showed a symmetrical chest wall with an increased antero posterior dimension and diminished inspiratory expansion. Auscultation revealed harsh inspiratory and expiratory bilateral diffuse rhonchi and fine scat tered expiratory wheezing. A chest X-ray showed bilateral prominence of mediastinal/cardiac shadows and increased reticular pulmonary markings, particu larly over the lower lung zones. He had markedly restricted ventilatory function on spirometry, with FVC = 3.3 1 (75% predicted), FEV, = 2.5 1 (74% predicted) and V^ = 60 1/min (39% predicted). Like his brother and father, he was diagnosed with talc pneumoconiosis. His disease progressed, and in <2 yr he was placed on permanent total disability. He died at age 58, 15 yr after presentation. The post-mortem revealed a biphasic diffuse pleural mesothelioma encasing the left lung, which had not been suspected during life. It is noteworthy that `congestive heart failure' was the only listed cause of death--there w as no mention of mesothelioma on the death certificate. DISCUSSION AND CONCLUSIONS We have found a continued trend of increased mesothelioma mortality at 5-10 times the back ground rate in Jefferson County from 1982 to 1997, with five new male cases (two expected) and three new female cases (0.5 expected). We also show that increasing talc exposure duration is associated with an increase in lung burden of both fibrous and non fibrous talc. Asbestos bodies were also seen in elevated concentration in most men with >10 yr exposure who had not been diagnosed with meso thelioma. The concentrations of each fiber type from mesothelioma and non-mesothelioma cases were similar, except for a high tremolite concentration in case 2. There was no significant difference found between non-mesothelioma and mesothelioma miners with regard to length and width of the tremolite and talc fibers (Tables 4 and 5), supporting our hypo thesis that they were exposed to dust with similar Table 3. Lung-retained particulate analyses of mesothelioma and non-mesothelioma cases Age at death Years of talc mining Diagnosis* Asbestos bodies6 Asbestos fibers2 Anthophyllite Tremolite/actinolite Chrysotile Talc (fibrous)' Talc (non-fibrous)d Silicad Mesotheliomas 1 2 58 52 22 4 ATM ATM 350 93 5 n/d 2 1110 5 21 46 96 37 146 7 n/d Non-mesotheliomas A B C 49 58 60 21 21 18 ATSC ATS ATP 200 10 980 12 85 64 i 105 7 7 188 10 24 716 4 7 511 60 n/a 15 10 n/a D 63 30 ATSP 890 E 66 23 ATPC 417 4 14 17 31 21 9 157 195 139 n/a 68 n/a F G H 71 71 76 25 2 10 ATP N1 Pn 4850 i 10 n/d 0.04 0.4 43 0.07 0.9 19 0.18 2.6 233 0.1 3.1 51 1 1 n/d 1 1 n/a, not available; n/d, not detected. *N1, normal; Pn, pneumonia; A, asbestosis; T, talcosis; S, silicosis; P, pleural plaques; M, mesothelioma; C, lung cancer. bThousands of bodies/gram dry lung. cMillions of fibers/gram dry lung. dMillions of non-frbrous particles/ml lung. Mesothelioma in asbestiform fiber-bearing talc mines 135 Table 4. Dimensional analysis for lung fibers in two New York State talc miners with immunohistochemically diagnosed malignant mesothelioma Fiber type Actinolite Anthophyllite Chrysotile Tremolite Talc na Width (pm) Xe Min Max 1 0.20 - ~ 6 0.15 0.06 0.30 5 0.05 0.03 0.06 38 0.22 0.10 0.40 54 0.20 0.05 1.00 Length (pm) ARb X Min Max 4.6 - - 23 10.6 3.9 30.2 90 4.1 1.9 6.1 93 4.5 1.7 10.6 26 5.3 1.4 53.0 43 ' aNumber of fibers measured. bMean aspect ratio = length x width-1. cGeometric mean. Table 5. Dimensional analysis for lung fibers in eight New York State talc miners with pulmonary disease other than mesothelioma Fiber type Actinolite Anthophyllite Chrysotile Tremolite Talc na Width (pm) X Min Max 7 0.18 0.12 0.25 85 0.24 0.05 1.60 33 0.08 0.04 0.40 51 0.34 0.04 1.00 284 0.33 0.06 2.80 Length (pm) ARh X Min Max 3.4 2.5 5.4 20 7.7 1.6 146.0 56 7.4 2.1 36.1 133 5.3 1.5 17.0 24 6.4 1.3 219.0 30 aNumber of fibers measured. bMean aspect ratio = length x width-1. cGeometric mean. fiber dimensions. Finally, in all of the 10 cases analyzed, only a single commercial amphibole fiber was found. New York talc miners are exposed to a mixture of platy talc, silica and fibrous minerals, resulting in a disease process much more complex than pure talcosis. The asbestiform fibers in the New York talc miners' lungs are a mixture of talc, tremolite and related mineral series. Our results indicate that mesos continue to occur at high rates in counties where New York talc mining occurs. Furthermore, New York talc miners without evidence of commercial amphi bole asbestos exposure develop mesos. Talc miners with mesos have lung fiber burdens similar to those without, indicating comparable exposures. Increased public health attention to the risks of exposure to New York talc is indicated. Acknowledgements--M.J.H. was a Post Sophomore Fellow in Pathology during part of this work. Supported by Department of Pathology, SUNY Upstate Medical University. REFERENCES Abraham JL, Burnett BR. (1983) Quantitative analysis of inorganic particulate burden in situ in tissue sections. Scanning Electron Microsc (Part 2); 681-96. Abraham JL, Burnett BR, Hunt A. (1991) Development and use of a pneumoconiosis database of pulmonary inorganic particulate burden in over 400 lungs. Scanning Microsc; 5: 95-104. Enterline P, Henderson B. (3987) Geographic patterns for pleural mesothelioma deaths in the United States, 1968-81. J Natl Cancer Inst; 79: 31-7. Kleinfeld M, Messite J, Kooyman O, Zaki MH. (1967) Mortal ity among talc miners and millers in New York State. Arch Environ Health; 14: 666-7. Merewether ERA. (1930) Occurrence of pulmonary fibrosis and other pulmonary affections in asbestos workers. J Ind Hyg; 12: 198. Porro FW, Patton JR, Hobbs AA. (1942) Pneumoconiosis in the talc industry. Am J Roentgen; 42: 507-24. Siegal W, Smith AR, Greenburg L. (1943) The dust hazard in tremolite talc mining, including roentgenological findings in talc workers. Am J Roentgen; 49; 11-29. Vianna NJ, Maslowsky J, Robert S, Spellman G, Patton B. (1981) Malignant mesothelioma; epidemiologic patterns in New York State. NY State J Med; 81: 735-8.